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Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare bleeding disorder of the fetus/newborn caused by development of maternal alloantibodies against fetal human platelet antigens (HPAs), predominantly HPA-1a. Currently there are no treatments available to prevent maternal alloimmunization to HPAs or FNAIT., Methods: This proof-of-concept study (EudraCT Number: 2021-005380-49) was designed to assess the ability of subcutaneous (SC) RLYB212, a monoclonal anti-HPA-1a antibody, to eliminate HPA-1a positive platelets in an antigen challenge model of a 30 mL fetal-maternal hemorrhage. Subjects were randomized to receive a single SC dose of RLYB212 or placebo on day 1 in a single-blinded manner, followed by transfusion of 10 × 10^9 HPA-1a positive platelets on day 8., Results: Four subjects received 0.09 mg SC RLYB212, 5 received 0.29 mg SC RLYB212, and 2 received placebo. RLYB212 achieved rapid elimination of HPA-1a positive platelets in a concentration-dependent manner, with concentrations as low as 3.57 ng/mL meeting the prespecified proof-of-concept criterion of ≥90% reduction in platelet elimination half-life vs placebo. Following HPA-1a positive platelet transfusion, a rapid decline was observed in the concentration of RLYB212 over a period of 2 to 24 hours, corresponding to the time needed for RLYB212 to bind to ~10% of HPA-1a on cell surfaces. RLYB212 was well tolerated with no reports of drug-related adverse events., Conclusion: The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies., Competing Interests: B.S., J.KK, and M.Kj. are stockholders of Prophylix AS, a Norwegian biotech company, that obtained the license of the monoclonal antibody 26.4 from UiT – the Arctic University of Norway, Tromsø, Norway, which was later purchased by Rallybio. J.KK consults for Rallybio and Janssen Pharmaceuticals, and receives honoraria from these two companies. M.Kj consults for Rallybio and receives support for attending meetings and/or travel and honoraria from Rallybio. F.B receives grants or contracts from Janssen Pharmaceuticals, Chugai Pharmaceuticals, and Roche; consults for Janssen Pharmaceuticals, Cilag, Novartis, Amgen, Lilly, UCB, Pfizer, AbbVie, Acelyrin, GSK, Chugai Pharmaceuticals, and Roche; receives honoraria from Janssen Pharmaceuticals, Cilag, Novartis, Amgen, Lilly, UCB, Pfizer, AbbVie, Acelyrin, Sandoz, AstraZeneca, and Chugai Pharmaceuticals; and receives support for attending meetings and/or travel from AbbVie and UCB. R.A., D.S., and K.P. are employees of Rallybio and are stockholders of Rallybio. German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH has a contract with Rallybio for the presented study. The remaining authors declare no competing financial interests., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Patients with psoriatic arthritis (PsA) require treatment providing durable long-term efficacy in different disease domains as well as safety. We present 100-week efficacy and safety results of risankizumab in patients with active PsA and previous inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR)., Methods: KEEPsAKE 1 (NCT03675308) is a global phase 3 study, including a 24-week, double-blind, placebo-controlled and ongoing open-label extension periods. Patients were randomized 1:1 to receive risankizumab 150 mg or placebo at baseline and weeks 4 and 16. After week 24, all patients received open-label risankizumab every 12 weeks thereafter. Patients were evaluated through 100 weeks. Endpoints included achieving ≥ 20% reduction in American College of Rheumatology criteria for symptoms of rheumatoid arthritis (ACR20), minimal disease activity (MDA; defined as ≥ 5/7 criteria of low disease activity and extent), and other measures., Results: Overall, 828/964 (85.9%) patients completed week 100. For patients receiving continuous risankizumab, 57.3%, 70.6%, and 64.3% achieved ACR20 at weeks 24, 52, and 100, respectively. For the placebo/risankizumab cohort, 33.5% achieved ACR20 at week 24 but increased after switching to active treatment at weeks 52 (63.7%) and 100 (62.1%). In ACR20 responders at week 52, 81.2% of both treatment cohorts maintained response at week 100. MDA was achieved by 25.0%, 38.3%, and 38.2% of the continuous risankizumab cohort at weeks 24, 52, and 100. In the placebo/risankizumab cohort, 10.2% achieved MDA at week 24, increasing at weeks 52 (28.0%) and 100 (35.2%). MDA response was maintained at week 100 in week 52 responders in the continuous risankizumab (75.5%) and placebo/risankizumab cohorts (78.2%). Similar trends were observed for other efficacy measures. Risankizumab was generally well tolerated through 100 weeks., Conclusions: For patients with active PsA who are csDMARD-IR, risankizumab demonstrated durable long-term efficacy and was generally well tolerated, with a consistent long-term safety profile., Trial Registration: ClinicalTrials.gov identifier, NCT03675308., (© 2024. The Author(s).)

Background and Aims: In lipidomic and metabolomic studies, pre-analytical pitfalls enhance the risk of misusing resources such as time and money, as samples that are analyzed may not yield accurate or reliable data due to poor sample handling. Guidance and pre-analytic know-how are necessary for translation of omics technologies into routine clinical testing. The present work aims to enable decision making regarding sample stability in every phase of lipidomics- and metabolomics-centered studies., Materials and Methods: Data of multiple pre-analytic studies were aggregated into a database. Flexible approaches for evaluating these data were implemented in an RShiny-based web-application, tailored towards broad applicability in clinical and bioanalytic research., Results: Our "Application for lipid stability evaluation & research" - ALISTER facilitates decision making on blood sample stability during lipidomic and metabolomic studies, such as biomarker research, analysis of biobank samples and clinical testing. The interactive tool gives sampling recommendations when planning sample collection or aids in the assessment of sample quality of experiments retrospectively., Conclusion: ALISTER is available for use under https://itmp.shinyapps.io/alister/. The application enables and simplifies data-driven decision making concerning pre-analytic blood sample handling and fits the needs of clinical investigations from multiple perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: For chronic diseases such as axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PsO), treatment goals include remission or at least low disease activity (LDA) by 12 weeks. Improvements in symptoms such as pain and fatigue should also be treatment goals., Methods: ADEQUATE was a German, prospective, non-interventional study to evaluate the proportion of patients with rheumatoid arthritis, PsA, axSpA, or PsO who, in routine clinical practice, benefit from the continuation of treatment with etanercept (ETN) beyond 12 weeks, even when their treatment goals have not yet been reached. Patient-reported outcomes (PROs) and changes in concomitant glucocorticoid use were also recorded. This article focuses on results for patients with axSpA and PsA; data for patients with PsO are described briefly., Results: In total, 305, 254, and 70 patients with axSpA, PsA, and PsO, respectively, were included. Rates of remission at week 12 and week 24, respectively, were 19% and 18% for axSpA, 38% and 51% for PsA, and 7% and 19% for PsO. Rates of LDA at week 12 and week 24, respectively, were 39% and 45% for axSpA, 50% and 60% for PsA, and 34% and 51% for PsO. Extending treatment up to 52 weeks was associated with stable rates of or further increases in remission and LDA rates. Improvements in pain, fatigue, and depression (axSpA, PsA, and PsO) and reductions in concomitant glucocorticoid use (axSpA and PsA) were observed. No new safety signals were detected., Conclusion: These findings confirm the effectiveness and safety of ETN in routine clinical practice for several indications and highlight potential benefits of continuing ETN treatment in patients who have not reached their treatment goals after 12 weeks. Additional benefits included improvements in PROs and reduction of concomitant glucocorticoids., Trial Registration: ClinicalTrials.gov NCT02486302., (© 2024. The Author(s).)

Background: Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis., Methods: The abatacept reversing subclinical inflammation as measured by MRI in ACPA positive arthralgia (ARIAA) study is a randomised, international, multicentre, double-blind, placebo-controlled trial done in 14 hospitals and community centres across Europe (11 in Germany, two in Spain, and one in the Czech Republic). Adults (aged ≥18 years) with ACPA positivity, joint pain (but no swelling), and signs of osteitis, synovitis, or tenosynovitis in hand MRI were randomly assigned (1:1) to weekly subcutaneous abatacept 125 mg or placebo for 6 months followed by a double-blind, drug-free, observation phase for 12 months. The primary outcome was the proportion of participants with any reduction in inflammatory MRI lesions at 6 months. The primary efficacy analysis was done in the modified intention-to-treat population, which included participants who were randomly assigned and received study medication. Safety analyses were conducted in participants who received the study medication and had at least one post-baseline observation. The study was registered with the EUDRA-CT (2014-000555-93)., Findings: Between Nov 6, 2014, and June 15, 2021, 139 participants were screened. Of 100 participants, 50 were randomly assigned to abatacept 125 mg and 50 to placebo. Two participants (one from each group) were excluded due to administration failure or refusing treatment; thus, 98 were included in the modified intention-to-treat population. 70 (71%) of 98 participants were female and 28 (29%) of 98 were male. At 6 months, 28 (57%) of 49 participants in the abatacept group and 15 (31%) of 49 participants in the placebo group showed improvement in MRI subclinical inflammation (absolute difference 26·5%, 95% CI 5·9-45·6; p=0·014). Four (8%) of 49 participants in the abatacept group and 17 (35%) of 49 participants in the placebo group developed rheumatoid arthritis (hazard ratio [HR] 0·14 [0·04-0·47]; p=0·0016). Improvement of MRI inflammation (25 [51%] of 49 participants in the abatacept group, 12 [24%] of 49 in the placebo group; p=0·012) and progression to rheumatoid arthritis (17 [35%] of 49, 28 [57%] of 49; HR 0·14 [0·04-0·47]; p=0·018) remained significantly different between the two groups after 18 months, 12 months after the end of the intervention. There were 12 serious adverse events in 11 participants (four [8%] of 48 in the abatacept group and 7 [14%] of 49 in the placebo group). No deaths occurred during the study., Interpretation: 6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk. The effects of the intervention persist through a 1-year drug-free observation phase., Funding: Innovative Medicine Initiative., Competing Interests: Declaration of interests JR reports receiving an unrestricted research grant from Sobi and Novartis, and speakers' honoraria and consulting fees from Bristol-Myers Squibb, Novartis, and Sobi. KT reports receiving speakers' honoraria and consulting fees from Novartis and Union Chimique Belge, and travel support from Celltrion. MØ reports receiving grants from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Union Chimique Belge, consulting fees from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and Union Chimique Belge, and honoraria for lectures, presentations, and speakers' bureaus from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and Union Chimique Belge. AK reports receiving honoraria for lectures and presentations, honoraria for participation on a data safety monitoring board (IIT TOLERA study), and honoraria for drug supply (IIT TOLERA study) from Bristol-Myers Squibb. BM reports receiving honoraria for lectures from Gilead, AbbVie, Janssen, and Pfizer. AJH reports receiving payment for a conditional grant from Galapagos and Novartis, consulting fees from AbbVie, Amgen, Galapagos, Janssen, Eli Lilly, Novartis, and Union Chimique Belge, and payment for lectures and presentations from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Eli Lilly, Medupdate, Novartis, Pfizer, Rheumaakademie, and Union Chimique Belge. XB reports receiving consulting fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Union Chimique Belge, honoraria for lectures and presentations from AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Union Chimique Belge, and payment for participation on a data safety monitoring board or an advisory board from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Union Chimique Belge. MFl reports receiving honoraria for presentations and lectures from AbbVie, Actelion, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Janssen, Medac, Menarini, Merck Sharp & Dohme, Novartis, Pfizer, Rheumaakademie, Roche, and Sobi. AR-R reports receiving consulting fees from Bristol-Myers Squibb, AbbVie, Pfizer, and Eli Lilly, payment for lectures and presentations from AbbVie, Bristol-Myers Squibb, Pfizer, Galapagos, Eli Lilly, Merck Sharp & Dohme, Union Chimique Belge, Sanofi, and Roche, payment for expert testimony from AbbVie and Galapagos, support for attending meetings or travel (or both) from Pfizer and Sanofi, participating on a data safety monitoring board for R-Pharm, and having a leadership or fiduciary role in the Swiss Rheumatology Society. RV reports receiving payment for lectures and presentations from AbbVie, AstraZeneca, Galapagos, GlaxoSmithKline, Novartis, Janssen–Cilag, and Pfizer, institutional support for attending meetings or travel (or both) from AbbVie, Galapagos, and Janssen–Cilag, institutional grants from Novartis and Pfizer, and participating on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Novartis, GlaxoSmithKline, and Union Chimique Belge. NV reports receiving honoraria for lectures and presentations and support for attending scientific meetings and congresses (congress fee and travel expenses) from Bristol-Myers Squibb. JT reports receiving an unrestricted research grant from Bristol-Myers Squibb, consulting fees from AbbVie, AstraZeneca, Novartis, GlaxoSmithKline, Eli Lilly, and Vifor, support for attending a meeting from Galapagos and Bristol-Myers Squibb, and participating on an advisory board for Novartis. EF reports receiving honoraria for lectures and presentations from AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Sobi, support for attending meetings from Novartis, and institutional grants from Eli Lilly, Novartis, and Galapagos. KK reports receiving honoraria from Union Chimique Belge for participation in an advisory board and reports payment for presentations from AbbVie, Novartis, and Union Chimique Belge. JS reports receiving honoraria for lectures and presentations from AbbVie, Bristol-Myers Squibb, Union Chimique Belge, Pfizer, Novartis, and Amgen, support for attending meetings from Union Chimique Belge and Janssen, and participating on an advisory board from AbbVie, Novartis, and Union Chimique Belge. EN reports receiving institutional payment from Pfizer and Eli Lilly, and payment for lecturing from AbbVie, Pfizer, and Eli Lilly. GS reports receiving speakers' honoraria and consulting fees from Bristol-Myers Squibb, Cabaletta, Janssen, Kyverna, Miltenyi, and Novartis. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors., Methods: Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52., Results: A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to ‍52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52., Conclusions: Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52., Competing Interests: Competing interests: LCC: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer and UCB Pharma; speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer and UCB Pharma. Associate Editor of RMD Open. RL: Consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, Pfizer, Novartis, and UCB Pharma; owner of Rheumatology Consultancy BV, an AMS company under Dutch law. On the Editorial Board of RMD Open. IBM: Consulting fees and honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Eli Lilly, Evelo, Janssen, Moonlake Pharma, Novartis and UCB Pharma; research support from BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis and UCB Pharma. On the Editorial Board of RMD Open. PJM: Research grants from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. CTR: Research for AbbVie; consultant for AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma. YT: Speaking fees and/or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho; received grants from Chugai, Eisai, Mitsubishi-Tanabe and Taisho. On the Editorial Board of RMD Open. AA: Honoraria and/or research grants from AbbVie, Amgen, BMS, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical Co. and UCB Pharma. FB: Consultant and/or speaker and/or investigator for AbbVie, Affibody, Amgen, BMS, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MoonLake Pharma, MSD, Novartis, Pfizer, Roche, Sandoz and Sanofi. DDG: Consultant and/or received grant support from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB Pharma. LG: Grants from AbbVie, Biogen, Eli Lilly, Novartis, Sandoz and UCB Pharma; personal fees from AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz and UCB Pharma. AMO: Research grants to Johns Hopkins University from AbbVie, Amgen, and Janssen; consulting fees from BMS, Janssen, Sanofi and UCB Pharma. ABG: Received research/educational grants from AnaptypsBio, BMS, Highlights Therapeutics, Janssen, Moonlake Immunotherapeutics AG, Novartis and UCB Pharma, (all paid to Mount Sinai School of Medicine); Received honoraria as an advisory board member and consultant for Amgen, AnaptypsBio, Avotres Therapeutics, BMS, Boehringer Ingelheim, Dice Therapeutics, Eli Lilly, Highlights Therapeutics, Janssen, Novartis, Sanofi, UCB and Xbiotech. RBW: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis and UCB Pharma; honoraria from Astellas, DICE Therapeutics, GSK and Union Therapeutics. BI: Shareholder of AbbVie, GSK and UCB Pharma; employee of UCB Pharma. RB and JC: Employees and shareholders of UCB Pharma. VS: Employee of UCB Pharma. JFM: Consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies., Methods: Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses., Results: Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs., Conclusion: The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to support short-term planning of resources and medication that can be translated to future pandemics are still missing. A workflow was established to identify a predictor for short-term COVID-19 disease progression in the acute phase of intensive care patients to support clinical decision-making., Methods: Thirty-two patients with SARS-CoV-2 infection were recruited on admission to the ICU and clinical data collected. During their hospitalization, plasma samples were acquired from each patient on multiple occasions, excepting one patient for which only one time point was possible, and the proteome (Inflammation, Immune Response and Organ Damage panels from Olink® Target 96), metabolome and lipidome (flow injection analysis and liquid chromatography-mass spectrometry) analyzed for each sample. Patient visits were grouped according to changes in disease severity based on their respiratory and organ function, and evaluated using a combination of statistical analysis and machine learning. The resulting short-term predictor from this multi-omics approach was compared to the human assessment of disease progression. Furthermore, the potential markers were compared to the baseline levels of 50 healthy subjects with no known SARS-CoV-2 or other viral infections., Results: A total of 124 clinical parameters, 271 proteins and 782 unique metabolites and lipids were assessed. The dimensionality of the dataset was reduced, selecting 47 from the 1177 parameters available following down-selection, to build the machine learning model. Subsequently, two proteins (C-C motif chemokine 7 (CCL7) and carbonic anhydrase 14 (CA14)) and one lipid (hexosylceramide 18:2; O2/20:0) were linked to disease progression in the studied SARS-CoV-2 infections. Thus, a predictor delivering the prognosis of an upcoming worsening of the patient's condition up to five days in advance with a reasonable accuracy (79 % three days prior to event, 84 % four to five days prior to event) was found. Interestingly, the predictor's performance was complementary to the clinicians' capabilities to foresee a worsening of a patient., Conclusion: This study presents a workflow to identify omics-based biomarkers to support clinical decision-making and resource management in the ICU. This was successfully applied to develop a short-term predictor for aggravation of COVID-19 symptoms. The applied methods can be adapted for future small cohort studies., Competing Interests: Declaration of competing interest ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks., Methods: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes., Results: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52., Conclusion: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition., Trial Registration: ClinicalTrials.gov, NCT02745080., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The influence of sex on treatment outcomes during interleukin-12/23 therapy in patients with psoriatic arthritis (PsA) has not been explored., Objective: To conduct exploratory post hoc analyses of sex-stratified data from the MUST trial, an investigator-initiated, multicentre, phase 3b study in which patients with active PsA initiating treatment with open-label ustekinumab were randomised to treatment with placebo or methotrexate (MTX)., Methods: We evaluated baseline characteristics, key treatment outcomes and adverse events stratified by sex, with a focus on outcomes that did not include erythrocyte sedimentation rate (ESR) as a component due to the known elevation of ESR in females., Results: A total of 166 patients were treated with ustekinumab+MTX (37 female, 50 male) or ustekinumab+placebo (32 female, 47 male). At baseline, females had a significantly longer time since PsA diagnosis and greater impairment in physical function, but similar joint counts. At week 24, both females and males showed marked improvements to ustekinumab with or without MTX. Females generally had numerically reduced treatment responses compared with males, although differences did not achieve statistical significance. MTX did not show an overall effect on treatment outcomes, but was associated with faster enthesitis responses in males only. Adverse events were generally comparable, but females in the ustekinumab+MTX group had higher levels of gastrointestinal disorders., Conclusion: Females and males with PsA had differences in baseline characteristics, treatment responses and adverse events during therapy. A better understanding of sex-based differences in PsA may help optimise treatment., Competing Interests: Competing interests: MK received consulting fees or honoraria from Amgen, Janssen-Cilag, Lilly, Novartis and UCB and received travel support from UCB. UK received grant and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, BMS, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Hexal, Janssen, MSD, Novartis, onkowissen.de, Pfizer, Roche, UCB and Viatris and participated on a data safety monitoring or advisory board for the COPAGO trial, conducted by the German Ministry of Health. GRB received fees or honoraria for serving as a speaker and/or consultant from Abbvie, Galapagos, Janssen, Lilly, Novartis and UCB, meeting or travel support from Abbvie and Lilly and is the editor-in-chief of RMD Open. DMK received honoraria for serving as a speaker for Sanofi-Aventis. SF received scientific grants from Novartis, honoraria or fees for serving as a speaker and/or consultant from Abbvie, AstraZeneca, Chugai, Galapagos, Novartis, NovoNordisc and UCB, and travel or meeting support from Abbvie, Galapagos, Janssen Cilag, Novartis, SOBI and UCB. RB received honoraria or fees for serving as a speaker and/or consultant from Abbvie, BMS, Chugai, GSK, Galapagos, Novartis, Roche and Vifor and meeting or travel support from Chugai and Galapagos. MS received research support from Charité. FB received research support for this study from Janssen Cilag, consulting fees or honoraria from Abbvie, Acelyrin, Amgen, Janssen Cilag, Lily, Novartis, Pfizer and UCB, and meeting or travel support from Abbvie and UCB. ACF, TR, HK and JB have no competing interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Psoriatic arthritis (PsA) is a chronic inflammatory systemic disease whose activity is often assessed using the Disease Activity Score 28 (DAS28-CRP). The present study was designed to investigate the significance of individual components within the score for PsA activity. A cohort of 80 PsA patients (44 women and 36 men, aged 56.3 ± 12 years) with a range of disease activity from remission to moderate was analyzed using unsupervised and supervised methods applied to the DAS28-CRP components. Machine learning-based permutation importance identified tenderness in the metacarpophalangeal joint of the right index finger as the most informative item of the DAS28-CRP for PsA activity staging. This symptom alone allowed a machine learned (random forests) classifier to identify PsA remission with 67% balanced accuracy in new cases. Projection of the DAS28-CRP data onto an emergent self-organizing map of artificial neurons identified outliers, which following augmentation of group sizes by emergent self-organizing maps based generative artificial intelligence (AI) could be defined as subgroups particularly characterized by either tenderness or swelling of specific joints. AI-assisted re-evaluation of the DAS28-CRP for PsA has narrowed the score items to a most relevant symptom, and generative AI has been useful for identifying and characterizing small subgroups of patients whose symptom patterns differ from the majority. These findings represent an important step toward precision medicine that can address outliers., (© 2023. The Author(s).)

Objective: We investigated the impact of concomitant MTX on ustekinumab (UST) levels and antidrug antibody (ADA) formation in PsA and evaluated consequences in pharmacodynamics and pharmacokinetics., Methods: We conducted a post-hoc analysis on 112 PsA serum samples of subjects treated with open-label UST and either concomitant MTX (UST/MTX, n = 58) or placebo (UST/pbo, n = 54) obtained in a randomized (1:1), double-blind, multicentre trial. A validated antibody-binding-based multitiered testing was used to detect ADA and ADA with neutralizing capacity (nADA). The impact of MTX on UST immunogenicity was analysed by comparison of UST/pbo with UST/MTX cohorts at different time points. Patient- and disease-related predispositions for ADA formation were investigated with multiple linear regression analysis. Immunogenicity impact on pharmacokinetics, safety and efficacy was determined by cohort comparison between patients with and without ADA formation., Results: Over 52 weeks, 11 UST/pbo- and 19 UST/MTX-treated patients developed ADA (P > 0.05). In the UST/pbo cohort, the visit-dependent UST levels were in the range of 0.047 (0.05) -0.110 (0.07) µg/ml overall, and 0.037 (0.04)-0.091 (0.08) µg/ml in ADA-confirmed subjects. In UST/MTX-treated patients, the UST levels exhibited an intervisit variation in the range of 0.0502 (0.04)-0.106 (0.07) µg/ml overall and 0.029 (0.03)-0.097 (0.07) µg/ml in ADA positive subjects (P > 0.05). At week 52, ADA-confirmed patients did not differ significantly (P > 0.05) in safety or clinical outcomes from ADA-negative patients., Conclusion: Concomitant MTX had no significant impact on UST immunogenicity. Furthermore, ADA formation was not associated with impairments in UST safety, efficacy or trough levels., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03148860., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting, the Collaborative Research Network (CRN) met to present updates on several projects. These included the GRAPPA-Industry biomarker projects, Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Axial Involvement in Psoriatic Arthritis Cohort (AXIS) study, and the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES). The meeting concluded with a discussion on pathways to further academia-industry collaboration., (Copyright © 2023 by the Journal of Rheumatology.)

Background and Objective: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease affecting the musculoskeletal system, skin and nails. The aim is to characterize sociodemographic and clinical patient profiles documented in dermatologic and rheumatologic care., Patients and Methods: Data of 704 patients with PsA from the dermatological Psoriasis Registry PsoBest (PB) and 1066 patients from the rheumatological disease registry RABBIT-SpA (RS) were analyzed. Comparable anamnestic and clinical variables were identified and descriptively analyzed., Results: The mean age was 51.7 years in PB and 51.9 in RS. Disease duration of psoriasis was longer, mean cutaneous severity was higher in PB. However, more patients in RS vs. PB had tender joints and swollen joints. Mean Dermatology Life Quality Index was higher in PB and mean Health Assessment Questionnaire in RS. Patient reported global disease activity and pain were lower in PB. IL-23 inhibitors were used more frequently in PB, and TNF inhibitors in RS., Conclusions: Clinical specialization was associated with different clinical and treatment patterns of PsA. This may indicate a selection by dominant manifestation of psoriatic disease and potentially by effects of health care access. Psoriatic arthritis should be treated in a multidisciplinary approach considering all facets of this complex disease., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40-60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of patients with PsA and patients with moderate-to-severe PsO. This narrative review aims to summarize nail psoriasis data generated from IXE clinical trials in patients with PsA (SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H) and/or moderate-to-severe PsO (UNCOVER-1, -2, -3, IXORA-R, IXORA-S, and IXORA-PEDS) with an emphasis on head-to-head clinical trial data. Across numerous trials explored, IXE treatment was associated with greater improvement in resolution of nail disease versus comparators at week 24, results which were maintained up to and beyond week 52. Additionally, patients experienced higher rates of resolution of nail disease versus comparators at week 24 and maintained high levels of resolution up to week 52 and beyond. In both PsA and PsO, IXE demonstrated efficacy in treating nail psoriasis, and therefore may be an effective therapy option. Trial Registration: ClinicalTrials.gov identifier UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), UNCOVER-3 (NCT01646177), IXORA-PEDS (NCT03073200), IXORA-S (NCT02561806), IXORA-R (NCT03573323), SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), SPIRIT-H2H (NCT03151551)., (© 2023. The Author(s).)

Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations. In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for better short-term and long-term outcomes., Competing Interests: OF has received grants from AbbVie, Bristol Myers Squibb, Janssen, Eli-Lilly, Novartis, Pfizer and UCB. DS has received grants from AbbVie, Janssen, Eli-Lilly and Novartis. SK is an employee of and has stocks or stock options in Bristol Myers Squibb. LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli-Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli-Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. FB and MK have received grants/research support from AbbVie, Amgen, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli-Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli-Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. AB has received grants/research support from Pfizer, Bristol Myers Squibb, Galapagos and Schiper Medicine and received speaker fees from Chugai-Roche. AV, MKl and JMS – no conflicts of interest to declare. CSG has received grants/research support from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim Pharmaceuticals, Eli-Lilly, Istesso, Janssen, MedAnnex, MiroBio, Pfizer, UCB; worked as a consultant for AstraZeneca, Bristol Myers Squibb, Janssen, MedAnnex, MiroBio; and has been paid as a speaker for AbbVie and UCB. BBD was an employee and then a consultant of Novartis Pharma AG. CH is an employee of Novartis Pharma AG. SS has received institutional research support from Amgen (previously Celgene), Boehringer Ingelheim, Bristol Myers Squibb, Eli-Lilly, GSK, Janssen and UCB; consultancy/speaker fees from AbbVie, Amgen, AstraZeneca, Eli-Lilly, GSK, Janssen and UCB. MdW: Over the last 3 years Stichting Tools has received fees for lectures or consultancy provided by Maarten de Wit from Celgene, Eli-Lilly, Pfizer and UCB., (© The Author(s), 2023.)

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease that affects approximately 30% of psoriasis patients. In most cases, skin disease clearly precedes the musculoskeletal disease. Some studies suggest that targeted treatment may intercept the disease course and prevent psoriasis patients from developing PsA. A recent population-based retrospective analysis in 15 501 psoriasis patients evaluated the association between different biological treatment strategies and time to incident inflammatory arthritis based on data in a US electronic health records database. A cumulative incidence of 2.6 PsA cases per 100 person-years was determined. The multivariable regression analysis revealed a significantly lower risk of developing inflammatory arthritis in patients who had been prescribed interleukin (IL)-12/23 or IL-23 inhibitors compared with tumour necrosis factor (TNF) inhibitor-treated patients, whereas there was no significant difference in risk for patients prescribed inhibitors of IL-17 versus TNF. Although the analysis was based on a large set of clinical data and the findings were rigorously evaluated, there are some limitations in interpretation due to the study design. Prospective clinical trials are missing, and retrospective data analyses from clinical trials or population-based studies show conflicting results. Overall, the recent data on prevention of PsA in patients with psoriasis support the high need to characterise biomarkers of increased risk and perform prospective clinical trials to give a clear guidance on possibilities for disease interception in psoriatic disease., Competing Interests: Competing interests: MK received consulting fees or honoraria from Amgen, Janssen-Cilag, Lilly, Novartis and UCB, and received travel support from UCB, AbbVie and Janssen-Cilag. FB received consulting fees or honoraria from Abbvie, Acelyrin, Amgen, Janssen Cilag, Lily, Novartis, Pfizer and UCB, and meeting or travel support from Abbvie and UCB., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the potential of immunosuppressed patients to mount B-cell and T-cell responses to COVID-19 booster vaccination (third vaccination)., Methods: Patients with primary immunodeficiency (PID), immune-mediated inflammatory diseases (IMIDs) on CD20-depleting treatment with rituximab (RTX), or IMIDs treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological disease-modifying antirheumatic drug (bDMARDs) were included and assessed before (baseline visit (BL)) and 2, 4 and 8 weeks after COVID-19 booster vaccination. Serum B-cell responses were assessed by antibody levels against SARS-CoV-2 spike protein (anti-spike IgG antibody (S-AB)) and a surrogate virus neutralisation test (sVNT). T-cell responses were assessed by an interferon gamma release assay (IGRA)., Results: Fifty patients with PID (n=6), treated with RTX therapy (n=13), or treated with csDMARDs/bDMARDs (n=31) were included. At BL, anti-S-AB titres in PID and csDMARD/bDMARD-treated patients were low (although significantly higher than RTX patients); measures of B-cell-mediated response increased significantly after booster vaccination. In the RTX cohort, low BL anti-S-AB and sVNT values did not improve after booster vaccination, but patients had significantly elevated IGRA responses post booster vaccination compared with the other groups. csDMARD/bDMARD-treated patients showed the highest BL values in all three assays with greater increases in all parameters after booster vaccination compared with patients with PID., Conclusion: Patients with IMID on therapeutic B-cell depletion have low anti-S-AB and sVNT values before and after booster vaccination but show significantly higher levels of IGRA compared with other immunosuppressed patients, suggesting an underlying mechanism attempting to compensate compromised humoral immunity by upregulating T-cell responsiveness. PID appears to have a stronger impact on antiviral immune response than csDMARD/bDMARD treatment., Competing Interests: Competing interests: Fraunhofer ITMP, the sponsor of this study, supported MKo, MKl, SD, KH, HB, SC, GG and FB. NK received speaker's fees from Abbott Laboratories. HB received research support from the Fraunhofer Cluster of Excellence for Immune-mediated Diseases (a non-profit organisation). HFR has no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate long-term effectiveness and safety of subcutaneous tocilizumab (TCZ-SC) in the routine clinical care of patients with rheumatoid arthritis (RA)., Methods: ARATA (ML29087) was a prospective, multicentre, observational study of adult patients with active RA initiating therapy with TCZ-SC. The primary effectiveness outcome was the proportion of patients achieving DAS28-ESR <2.6 at week 104. Additional efficacy outcomes included individual DAS28-dcrit responses (improvement of ≥1.8 from baseline), CDAI remission (≤2.8), and patient-reported outcomes (PROs), including Work Productivity and Activity Impairment scores. Adverse event rates were used to evaluate safety and tolerability., Results: Between May 2014 and July 2018, 114 study centres in Germany enrolled 1,300 patients with RA who received at least one dose of TCZ-SC (mean age 57.3 [SD 12.5] years, mean DAS28-ESR of 4.9 [SD 1.3]). At week 104, 58.7% (365/622) patients achieved DAS28-ESR <2.6, 64.0% had an individual DAS28-dcrit response, and 31.4% (241/767) achieved CDAI remission. PROs, including patient global assessment, pain, and fatigue, showed marked improvements from baseline. Work outcomes, including absenteeism (missed work) and presenteeism (productivity while at work), also improved. Injection reactions were rare and no new safety signals occurred. Patients expressed a high level of satisfaction with treatment. Baseline patient characteristics and outcomes were similar for ARATA and ICHIBAN (an observational study of TCZ-IV in Germany), despite different formulations and time periods., Conclusions: The safety and effectiveness of TCZ-SC is maintained over 2 years during routine clinical care. TCZ-SC represents a convenient and effective option for RA patients who prefer SC administration.

Objective: PsA is a chronic disease with heterogeneous clinical manifestations requiring treatment options with long-term efficacy and safety. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated., Methods: KEEPsAKE 1 is an ongoing, global, phase 3 study with a 24-week, double-blind, placebo-controlled period (period 1) and an open-label extension period (period 2). In period 1, eligible patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16. At week 24 (period 2), all continuing patients received open-label risankizumab 150 mg every 12 weeks through week 208., Results: At week 24, 57.3% of risankizumab-treated patients (n = 483) achieved ≥20% improvement in ACR criteria (ACR20) vs 33.5% of placebo-treated patients (n = 481; P < 0.001). At week 52, 70.0% of patients who were randomized to receive continuous risankizumab therapy and 63.0% of patients who were randomized to receive placebo in period 1 and then receive risankizumab at week 24 achieved ACR20. Similar result trends were observed for other efficacy measures. Risankizumab was well tolerated through 52 weeks of treatment with a consistent safety profile from week 24 through week 52., Conclusion: In patients with active PsA who were csDMARD-IR, continuous risankizumab treatment demonstrated robust long-term efficacy and was well tolerated through 52 weeks of treatment., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, KEEPsAKE1, NCT03675308., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT., Objectives: To investigate whether a single dose of anti-HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a-negative participants as compared with placebo., Methods: This randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a- and HLA-A2-negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo., Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment-emergent adverse events were possibly related to treatment, both in RLYB211-treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks., Conclusion: These data support the hypothesis that anti-HPA-1a could be used as prophylaxis in women at risk of having an FNAIT-affected pregnancy., Competing Interests: Declaration of competing interests M.Kj., B.S., and J.KK. are stockholders of Prophylix AS, a Norwegian biotech company, which produced the study drug. M.Kj. and J.KK. are currently consultants for Rallybio, which is the sponsor of the study. R.A. and Z.B. are employees of Rallybio. J.KK. also provides consultancy services for ROS Therapeutics, Glycorex Transplantation AB, and Johnson & Johnson. German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH has a contract with Rallybio for the present study. The remaining authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Randomised clinical studies in psoriatic arthritis (PsA) do not always reflect patients in routine clinical practice. Large-scale data from routine practice are needed to better understand drug persistence, effectiveness and long-term safety of therapeutic agents., Methods: PsABIOnd is an international, prospective, observational study designed to collect long-term routine care data in patients with PsA who receive guselkumab (an interleukin-23 [IL-23] inhibitor) or an interleukin-17 (IL-17) inhibitor. Adult patients (≥ 18 years) with a confirmed diagnosis of PsA who are starting guselkumab or any approved IL-17 inhibitor as a first, second, third or fourth line of PsA treatment and who provide written informed consent will be eligible to participate. Participants will be followed for a maximum of 36 months (+3 months) from the start of treatment. Study visits will occur in line with the standard of care, approximately every 6 months, plus an additional visit at 3 months after the start of treatment. eDaily by PsABIOnd - aneHealth substudy, will document the impact of these treatments on wellbeing and symptoms in a subgroup of participants over a 24-week (+4 weeks) observation period on treatment., Planned Outcomes: The primary objective of PsABIOnd is to evaluate treatment persistence with guselkumab and IL-17 inhibitors. Data sources will include validated electronic patient-reported outcomes (ePROs) and physician-completed assessments. Safety data will be collected through reporting adverse events. The eDaily by PsABIOnd substudy will use wearable and digital technologies for continuous activity and sleep monitoring, and frequent patient eDiary and ePRO collection to provide a more detailed and comprehensive picture of PsA., Trial Registration: ClinicalTrials.gov identifier: NCT05049798., (© 2022. The Author(s).)

Background: Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) show certain overlaps: A subset of patients with PsA can develop axial involvement (axial PsA, axPsA), while a subset of patients with axSpA presents with psoriasis (axSpA+pso). Treatment strategy for axPsA is mostly based on axSpA evidence., Objectives: To compare demographic and disease-specific parameters of axPsA and axSpA+pso., Methods: RABBIT-SpA is a prospective longitudinal cohort study. AxPsA was defined based on (1) clinical judgement by rheumatologists; (2) imaging (sacroiliitis according to modified New York criteria in radiographs or signs of active inflammation in MRI or syndesmophytes/ankylosis in radiographs or signs of active inflammation in spine MRI). axSpA was stratified into axSpA+pso and axSpA without pso., Results: Psoriasis was documented in 181/1428 axSpA patients (13%). Of 1395 PsA patients, 359 (26%) showed axial involvement. 297 patients (21%) fulfilled the clinical definition and 196 (14%) the imaging definition of axial manifestation of PsA. AxSpA+pso differed from axPsA regardless whether clinical or imaging definition was used. axPsA patients were older, more often female and less often HLA-B27+. Peripheral manifestations were more often present in axPsA than in axSpA+pso, whereas uveitis and inflammatory bowel disease were more common in axSpA+pso. Burden of disease (patient global, pain, physician global) was similar among axPsA and axSpA+pso patients., Conclusions: AxPsA differs from axSpA+pso in its clinical manifestations, irrespective of whether axPsA is defined clinically or by imaging. These findings support the hypothesis that axSpA and PsA with axial involvement are distinct entities, so extrapolation of treatment data from randomised controlled trials in axSpA should be performed with caution., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: PsA is a heterogeneous disease that impacts many aspects of social and mental life, including quality of life. Risankizumab, an antagonist specific for IL-23, is currently under investigation for the treatment of adults with active PsA. This study evaluated the impact of risankizumab vs placebo on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) among patients with active PsA and inadequate response or intolerance to conventional synthetic DMARD (csDMARD-IR) in the KEEPsAKE 1 trial., Methods: Adult patients with active PsA (n = 964) were randomized (1:1) to receive risankizumab 150 mg or placebo. PROs assessed included the 36-Item Short-Form Health Survey (SF-36, v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQoL-5 Dimension-5 Level (EQ-5D-5L), Patient's Assessment of Pain, Patient's Global Assessment (PtGA) of Disease Activity, and Work Productivity and Activity Impairment-PsA (WPAI-PsA) questionnaire. Least squares (LS) mean change from baseline at week 24 was compared between risankizumab and placebo., Results: At week 24, differences between groups were observed using LS mean changes from baseline in SF-36 physical component summary and mental component summary; FACIT-Fatigue; EQ-5D-5L; Patient's Assessment of Pain; PtGA; all eight SF-36 domains (all nominal P < 0.001); and the WPAI-PsA domains of impairment while working (presenteeism), overall work impairment and activity impairment (all nominal P < 0.01)., Conclusion: Risankizumab treatment resulted in greater improvements in HRQoL, fatigue, pain and work productivity in patients with active PsA who have csDMARD-IR, when compared with placebo., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03675308., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A. This study compared the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α (TNFα) inhibitors., Methods: BE COMPLETE was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial conducted across 92 sites (including hospitals, clinics, and research centres) in 11 countries (Australia, Canada, Czech Republic, Germany, Hungary, Italy, Japan, Poland, Russia, the UK, and the USA). Eligible patients were aged 18 years or older with adult-onset psoriatic arthritis (meeting the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening) with a history of inadequate response or intolerance to treatment with one or two TNFα inhibitors for either psoriatic arthritis or psoriasis. We stratified patients with active psoriatic arthritis by region and previous TNFα inhibitor use. Patients were randomly assigned (2:1) to receive subcutaneous bimekizumab 160 mg every 4 weeks or placebo by an interactive-voice and web-response system on the basis of a predetermined randomisation schedule. The primary endpoint was the proportion of patients with 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses were done in the randomised population. The safety analysis set comprised patients who received one or more doses of study treatment. This trial was registered at ClinicalTrials.gov, NCT03896581, and is completed., Findings: Between March 28, 2019, and Feb 14, 2022, 556 patients were screened and 400 patients were randomly assigned to bimekizumab 160 mg every 4 weeks (n=267) or placebo (n=133). The primary and all hierarchical secondary endpoints were met at week 16. 116 (43%) of 267 patients receiving bimekizumab reached ACR50, compared with nine (7%) of 133 patients receiving placebo (adjusted odds ratio [OR] 11·1 [95% CI 5·4-23·0], p<0·0001). 121 (69%) of 176 patients with psoriasis affecting at least 3% body surface area at baseline who received bimekizumab reached 90% or greater improvement in the Psoriasis Area and Severity Index (PASI90), compared with six (7%) of 88 patients who received placebo (adjusted OR 30·2 [12·4-73·9], p<0·0001). Treatment-emergent adverse events up to week 16 were reported in 108 (40%) of 267 patients receiving bimekizumab and 44 (33%) of 132 patients receiving placebo. There were no new safety signals and no deaths., Interpretation: Bimekizumab treatment led to superior improvements in joint and skin efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNFα inhibitors. The safety profile of bimekizumab was consistent with previous phase 3 studies in patients with plaque psoriasis, and studies of IL-17A inhibitors., Funding: UCB Pharma., Competing Interests: Declaration of interests JFM reports work as a consultant or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. RL reports consultancy fees from Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth; research grants from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth; and speaker's bureau fees from Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth. IBM reports consulting fees and honoraria from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma; and research support from BMS, Boehringer Ingelheim, Celgene, Janssen, and UCB Pharma. PJM reports research grants from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, and UCB Pharma; and speakers' bureau fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma. CTR reports research for AbbVie, Amgen, and UCB Pharma; and consultancy for Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. YT reports speaking fees or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi-Tanabe, and Pfizer; and research grants from Asahi-Kasei, AbbVie, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, and Takeda. AA reports honoraria or research grants from AbbVie, Amgen, BMS, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi-Tanabe, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma. FB reports work as a consultant, speaker, or investigator for AbbVie, Affibody, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MSD, MoonLake, Novartis, Pfizer, Roche, Sandoz, and Sanofi. DDG received grants from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; and consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. LG reports non-financial support from UCB Pharma during the conduct of the study; grants from Amgen, Eli Lilly, Galapagos, Pfizer, Sandoz, and UCB Pharma; personal fees from AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Sandoz, and UCB Pharma; and non-financial support from AbbVie, Janssen, Novartis, Pfizer, and UCB Pharma outside the submitted work. ABG reports honoraria as an advisory board member, non-promotional speaker, or consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech (stock options); and research or educational grants from AnaptysBio, BMS, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, and UCB Pharma (all funds go to the Icahn School of Medicine at Mount Sinai). DT reports honoraria for participation on advisory boards as a speaker and for consultancy from AbbVie, Almirall, Amgen, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Samsung, Sanofi Genzyme, and UCB Pharma; and research grants from LEO Pharma and Novartis. RBW reports consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma; and honoraria from Astellas, DiCE, GSK, and Union. BI is an employee of UCB Pharma, and stockholder of AbbVie, GSK, and UCB Pharma. DA, RB, VS, and JC are all employees and stockholders of UCB Pharma. LCC reports grants and research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma; paid consultancy for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma; and speaker fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB Pharma., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The role of methotrexate in combination with biological agents in patients with psoriatic arthritis remains unclear. The MUST phase 3b trial aimed to compare the efficacy of ustekinumab plus placebo with ustekinumab plus methotrexate in patients with active psoriatic arthritis., Methods: In this investigator-initiated, randomised, multicentre, placebo-controlled, phase 3b non-inferiority trial done in 22 centres in Germany, patients with active psoriatic arthritis received open-label ustekinumab and were randomly assigned (1:1) to masked concomitant therapy with placebo or methotrexate (ongoing or new). The primary outcome was non-inferiority of mean Disease Activity Score-28 joints (DAS28) at week 24 for ustekinumab monotherapy (ustekinumab plus placebo) versus ustekinumab combination therapy (ustekinumab plus methotrexate), stratified by previous methotrexate treatment. The key secondary analysis was non-inferiority of DAS28 at week 52. The primary analysis was based on a stratified van Elteren test with an α of 2·5% and a non-inferiority margin of 12·5% by Mann-Whitney estimator. Adverse events and serious adverse events were assessed. This study is registered with ClinicalTrials.gov, NCT03148860., Findings: Between Jan 24, 2017, and April 12, 2021, 186 patients with active psoriatic arthritis were screened, of whom 173 (93%) patients were enrolled and randomly assigned (1:1) to receive concomitant methotrexate therapy (n=88) or placebo (n=85). 84 patients were receiving methotrexate at baseline, and 89 patients had no previous methotrexate treatment. 166 (96%) patients (87 in the ustekinumab plus methotrexate group and 79 in the ustekinumab plus placebo group) were included in the safety and efficacy analyses at week 24 (69 [42%] female; 97 [58%] male; mean age 48·2 years [SE 1·1]). Ustekinumab plus placebo was non-inferior to ustekinumab plus methotrexate in DAS28 at week 24 (2·9 [SD 1·31] vs 3·1 [1·42]); the stratified Mann-Whitney estimator for treatment comparison was 0·5426 (95% CI 0·4545-0·6307). Non-inferiority for ustekinumab plus placebo was also observed in DAS28 at week 52. Serious adverse events occurred in seven (9%) patients in the ustekinumab plus placebo group and eight (9%) patients in the ustekinumab plus methotrexate group. No specific serious adverse events affected more than one patient, and there were no deaths., Interpretation: Interleukin (IL)-12 and IL-23 inhibition with ustekinumab is an effective treatment for psoriatic arthritis independent of methotrexate use; concomitant methotrexate did not increase efficacy of ustekinumab (based on DAS28). On the basis of these data, there is no evidence to support the addition or maintainance of methotrexate when initiating ustekinumab in patients with active psoriatic arthritis., Funding: Janssen Cilag., Competing Interests: Declaration of interests MK received grants or contracts from BMS, Bionorica, Iron4u, Janssen-Cilag, LEO, Novartis, and Pfizer and received travel support or honoraria or fees for serving as a speaker, consultant and/or advisory board member from Abbvie, Lilly, Janssen-Cilag, Novartis, Pfizer, and UCB. GRB received honoraria or fees for serving as a speaker and/or consultant from Abbvie, Amgen, BMS, Galapagos, Lilly, MSD, Pfizer, Roche, and Sanofi. UK received scientific grants from AbbVie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, Pfizer and honoraria or fees for serving as a speaker and/or consultant from Abbvie, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, and UCB. JR received scientific grants from Novartis and Sobi, and honoraria or fees for serving as a speaker and/or consultant from Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, and UCB. SM-P received honoraria or fees for serving as a speaker and/or consultant from AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, and Novartis. HB received travel support or honoraria or fees for speaking from Janssen Cilag and research support from the Fraunhofer Cluster of Excellence for Immune-mediated diseases (CIMD). FB received research support from Janssen Cilag, the Fraunhofer Cluster of Excellence for Immune-mediated diseases (CIMD), and LOEWE Zentrum Translational Medicine and Pharmacology, grants or contracts from BMS, Bionorica, Iron4u, Janssen-Cilag, LEO, Novartis, and Pfizer, and meeting support or honoraria or fees for serving as a speaker, consultant, and/or advisory board member from Abbvie, Affibody, Amgen, Boehringer Ingelheim, Galapagos, GSK, Janssen Cilag, Lilly, MoonLake, MSD, Novartis, Pfizer, Sandoz, Sanofi, and UCB. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known., Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated., Results: Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose., Conclusions: Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity.

Objectives: To evaluate the ability of fluorescence-optical imaging (FOI) to detect preclinical musculoskeletal inflammatory signs in patients with skin psoriasis at risk of developing psoriatic arthritis (PsA)., Methods: This investigator-initiated prospective exploratory study evaluated adult patients with psoriasis with musculoskeletal complaints and/or nail psoriasis within the last 6 months. Patients underwent a comprehensive rheumatological clinical examination (CE) along with musculoskeletal ultrasound (MSUS) and FOI of both hands at a single visit. Patients with CE-/MSUS-/FOI+ findings had MRI performed on the symptomatic or dominant hand within 7 days. If MRI was negative, the patients were followed over 2 years for the onset of clinically manifest PsA., Results: A total of 389 patients were referred from dermatology centres and evaluated at 14 rheumatology sites in Germany. Seventy-seven (20%) patients with CE-/US-/FOI- were considered to have psoriasis only. PsA was diagnosed in 140/389 patients (36%) based on CE alone and in another 55 patients (14%) by additional MSUS; overall, 50% of the patient cohort was diagnosed with PsA. One hundred sixteen patients (30%) were FOI+ (CE-) of which 40 (37%) were FOI+/MRI+. In the 2-year follow-up of the FOI+/CE- patients, clinical PsA was confirmed in another 12%., Conclusion: FOI is a promising method for the detection of signs of musculoskeletal inflammation in hands that may serve as an early imaging biomarker for transitions from psoriasis to PsA. This imaging technique has the potential to detect PsA in at-risk patients with psoriasis, reduce time to PsA diagnosis and improve patient outcomes., Competing Interests: Competing interests: MK, ACF, TR, HB and FB are supported by Fraunhofer ITMP, the sponsor of this study. MK received research grants from Bionorica, BMS, Iron4u, LEO, Janssen-Cilag, Novartis and Pfizer and speaker’s fees, consulting fees and/or conference support from AbbVie, Janssen-Cilag, Lilly, Novartis, Pfizer and UCB. SGW participated in project planning boards with the owner of Xiralite GmbH and Pfizer as sponsor, but did not receive personal compensation. GRB is on the editorial board of RMD Open. SW received speaker’s fees and/or conference support from AbbVie, Gilead, Lilly, MSD, Mylan, Pfizer, Rheumaklinik Sendenhorst, Rheumatologische Fortbildungsakademie (Berlin), Rheumazentrum Rhein Ruhr, Sanofi, streamedup and UCB, and participated on data safety monitoring or advisory boards for AbbVie, BMS, Galapagos, Gilead, Lilly and UCB. BK received funding from Fraunhofer Institute for this study, speaker’s fees, conference support and/or advisory board fees from AbbVie, Boehringer Ingelheim, Celegen, Janssen, Lilly, Novartis, Pfizer. HB received research support from the Fraunhofer Cluster of Excellence for Immune-mediated Diseases (a non-profit organisation) and speaker’s fees, consulting fees and/or conference support from Janssen-Cilag and Roche. FB received grants/research support from Bionorica, BMS, Iron4u, Janssen-Cilag, LEO, Novartis and Pfizer, speaker’s fees, consulting fees and/or conference support from AbbVie, Affibody, Amgen, Boehringer-Ingelheim, Galapagos, GSK, Janssen-Cilag, Lilly, MoonLake, MSD, Novartis, Pfizer, Sandoz, Sanofi and UCB and serves on data safety monitoring or advisory boards for AbbVie, Amgen, Boehringer, Galapagos, Janssen-Cilag, Lilly, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks., Methods: In this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study. Efficacy assessments included American College of Rheumatology (ACR) responses, Psoriasis Area Severity Index (PASI) responses, minimal disease activity (MDA), and 28-joint Disease Activity Score based on C-reactive protein (DAS28[CRP])., Results: Of 185 randomized patients, 173 (93.5%) completed week 16 and 145 (78.4%) entered the open-label extension. Significantly more patients in each risankizumab arm achieved ACR20 at week 16 versus placebo (primary endpoint: pooled arms 1 + 2 [59.5%] versus placebo [35.7%]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P = 0.007). Similarly, significantly more patients in most risankizumab arms achieved ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) versus placebo at week 16. These benefits of risankizumab were maintained long term. Treatment-emergent adverse events were comparable across treatment arms. Risankizumab 150 mg was well tolerated over 76 weeks., Conclusions: Risankizumab improved joint and skin symptoms versus placebo in patients with active PsA over 16 weeks; improvements were sustained long term. Risankizumab was well tolerated over the long term with no new safety findings., Trial Registration Numbers: NCT02719171 and NCT02986373., (© 2022. The Author(s).)

Introduction: Psoriatic arthritis (PsA) is a chronic, progressive disease that places a significant burden on patients and healthcare systems. The SUSTAIN study collected real-world evidence on long-term effectiveness, impact on quality of life, and safety of ustekinumab treatment for PsA., Methods: SUSTAIN was a prospective, non-interventional study conducted in Germany. Patients with active PsA received ustekinumab for 160 weeks in routine clinical care, with assessments at baseline, week 4, and every 12 weeks thereafter. This analysis focuses on patients who remained in SUSTAIN until week 160., Results: Of 337 patients enrolled, 129 were documented at week 160, of which 123 (95.3%) had received previous PsA medication, including biologics. Decreases from baseline to week 4 were observed for tender joint count (TJC, 8.0 to 5.8) and swollen joint count (SJC, 4.5 to 3.1); these decreases continued to week 28 and were maintained to week 160 (1.0 and 0.4, respectively). Similarly, skin assessments in patients with PsA and psoriasis revealed improvement at week 4, which continued to week 28, with a sustained effect until week 160. Similar patterns of response were observed for patient-assessed pain, sleep quality, and health scores. Improvements in TJC, SJC, Psoriasis Area and Severity Index, and affected body surface area were observed irrespective of the number of prior biologic therapies used. Minimal disease activity was achieved by 36 (31.9%) patients at week 28, and by 38 (33.6%) at week 52. Ustekinumab-related adverse events (AEs) and serious AEs were reported in 61 (47.3%) and 4 (3.1%) patients, respectively. At week 160, 100% of patients assessed ustekinumab tolerability as good or very good., Conclusions: In a real-world setting, patients with active PsA who received ustekinumab until 160 weeks (3 years), including those who received prior biologic therapies, had a rapid onset of effect and sustained response to treatment, with high tolerability., Trial Registration: PEI NIS No. 290., (© 2022. The Author(s).)

Fluorescence optical imaging technique (FOI) is a well-established and valid method for visualization of changes in micro vascularization at different organ systems. As increased vascularization is an early feature of joint inflammation, FOI is a promising method to assess arthritis of the hands. But usability of the method is limited to the assessors experience as the measurement of FOI is semi-quantitative using an individual grading system such as the fluorescence optical imaging activity score (FOIAS). The goal of the study was to automatically and thus, objectively analyze the measured fluorescence intensity generated by FOI to evaluate the amount of inflammation of each of the subject's joints focusing on the distinction between normal joint status or arthritis in psoriatic arthritis patients compared to healthy volunteers. Due to the heterogeneity of the pathophysiological perfusion of the hands, a method to overcome the absoluteness of the data by extracting heatmaps out of the image stacks is developed. To calculate a heatmap for one patient, firstly the time series for each pixel is extracted, which is then represented by a feature value. Secondly, all feature values are clustered. The calculated cluster values represent the relativity between the different pixels and enable a comparison of multiple patients. As a metric to quantify the conspicuousness of a joint a score is calculated based on the extracted cluster values. These steps are repeated for a total number of three features. With this method a tendency towards a classification into unaffected and inflamed joints can be achieved. However, further research is necessary to transform the tendency into a robust classification model., Competing Interests: The authors have declared that no competing interests exist.

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients.

Background and Objectives: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS)., Methods: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)-based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92])., Results: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max =  - 0.65; RA patients: g*max = 0.72)., Conclusion: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment. Key Points • The effect of topical capsaicin may represent the extent of TRPV1 sensitization in rheumatoid arthritis. • The effect of topical capsaicin on the amplitude level of CHEPs can unmask neuropathic symptoms. • The effect of topical capsaicin on CHEPs and HPTs can show the long-term consequences and the treatment success of RA patients in remission., (© 2022. The Author(s).)

Objective: ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients., Methods: Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab., Results: At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (-2.8 [3.0] vs -1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes., Conclusion: A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes., Trial Registration: clinicaltrials.gov, NCT02771210., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA)., Methods: In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16., Results: ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p = 0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p≤0.05) in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response. Improvements were also seen in multiple exploratory endpoints with deucravacitinib treatment. The most common adverse events (AEs) (≥5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment., Conclusions: Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA., Trial Registration Number: NCT03881059., Competing Interests: Competing interests: PJM: research grants: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB; consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB. AAD: consulting and/or advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB; research grants: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and UCB. DvdH: consulting fees: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma; Director: Imaging Rheumatology. FB: research grants: Pfizer, Janssen, Chugai, Celgene and Roche; consultancies/speaker fees: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb and UCB Pharma. AJK: shareholder: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences and Novartis; paid consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research and Gilead Sciences; speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie. JN: research grants to foundation: AbbVie, Amgen, Eli Lilly, Genentech, Novartis, UCB, Pfizer, Gilead and Bristol Myers Squibb. SS, MN, SB: employees and shareholders of Bristol Myers Squibb. JK: employee of Bristol Myers Squibb at time of the study conduct., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: For rheumatoid arthritis (RA), the treat-to-target concept suggests attaining remission or at least low disease activity (LDA) after 12 weeks., Objectives: This German, prospective, multicenter, non-interventional study aimed to determine the proportion of patients with RA who achieved their treat-to-target aim after 12 and 24 weeks of etanercept (ETN) treatment in a real-life setting, as opposed to patients achieving their therapeutic target at a later timepoint (week 36 or 52)., Methods: A total of 824 adults with a confirmed diagnosis of RA without prior ETN treatment were included. Remission and LDA were defined as DAS28 < 2.6 and DAS28 ≤ 3.2, respectively., Results: The proportion of patients achieving remission was 24% at week 12 and 31% at week 24. The proportion of patients achieving LDA was 39% at week 12 and 45% at week 24. The proportion of patients achieving remission or LDA further increased beyond week 24 up to week 52. Improvement in pain and reduction in concomitant glucocorticoid treatment were observed. Improvements in patient-reported outcomes were also seen in patients who did not reach remission or LDA. No new safety signals were detected., Conclusions: A considerable proportion of patients with RA attained the target of remission or LDA after 12 weeks of ETN treatment. Even beyond that timepoint, the proportion of patients achieving treatment targets continued to increase up to week 52., Trial Registration: ClinicalTrials.gov Identifier: NCT02486302., (© 2022. The Author(s).)

Background: Many patients with psoriatic arthritis do not reach minimal disease activity (MDA) on methotrexate alone. This phase 4 open-label study aimed to compare attainment of MDA following introduction of adalimumab with methotrexate escalation in patients with psoriatic arthritis who do not reach MDA after an initial methotrexate course (≤15 mg every week)., Methods: CONTROL was a phase 4, randomised, two-part, open-label study conducted in 14 countries and 46 sites. We recruited patients with confirmed active psoriatic arthritis, naive to biologic disease-modifying antirheumatic drugs, with an inadequate response to 15 mg or less of methotrexate. In part 1, patients were randomly assigned (1:1) to receive either methotrexate 15 mg (oral or subcutaneous) every week with the addition of adalimumab 40 mg (subcutaneously) every other week (adalimumab plus methotrexate group) or methotrexate (oral or subcutaneous) escalation up to 25 mg every week (escalated methotrexate group). Randomisation was done using Interactive Response Technology and stratified by the duration of methotrexate treatment (≤3 months and >3 months). In this open-label study there was no masking; participants, people giving the interventions, those assessing outcomes, and those analysing the data were aware of group assignment. The primary endpoint was the proportion of patients who reached MDA at 16 weeks. After 16 weeks (part 2), patients who reached MDA (responders) had their current therapy maintained or modified, wheras patients who did not reach MDA (non-responders) had their therapy escalated until 32 weeks. The primary endpoint in part 2 was the proportion of patients who reached MDA at 32 weeks, analysed in all patients who received one or more doses of study drug. The study is registered with ClinicalTrials.gov, NCT02814175., Findings: Between Aug 5, 2016, and March 19, 2020, 245 of 287 patients initially assessed were enrolled in the study (50% men and 50% women; 92% of patients were White). 123 patients were randomly assigned to receive adalimumab plus methotrexate and 122 patients to receive escalated methotrexate. All 245 patients were included in the primary analysis, and 227 completed part 1 and entered part 2. A significantly higher proportion of patients reached MDA at 16 weeks in the adalimumab plus methotrexate group (51 [41%] patients) compared with the escalated methotrexate group (16 [13%] patients; p<0·0001). Efficacy was generally maintained through 32 weeks for patients who reached MDA at 16 weeks, with 41 (80%) of 51 adalimumab responders and ten (67%) of 15 methotrexate responders maintaining MDA at 32 weeks. Of adalimumab non-responders, 17 (30%) of 57 patients reached MDA at 32 weeks after adalimumab escalation to every week dosing. Among methotrexate non-responders, 50 (55%) of 91 reached MDA after adalimumab introduction. In part 1, two patients in the adalimumab plus methotrexate group reported serious adverse events; and in part 2, one adalimumab responder, three adalimumab non-responders, and three methotrexate non-responders reported serious adverse events. No new safety signals were identified., Interpretation: Results from this novel treatment-strategy trial support the addition of adalimumab over escalating methotrexate in patients with psoriatic arthritis not reaching MDA after an initial methotrexate course. Safety results were consistent with the therapies' known safety profiles., Funding: AbbVie., Competing Interests: Declaration of interests LCC reports funding from a National Institute for Health Research (NIHR) clinician scientist award; support from the NIHR Oxford Biomedical Research Centre; and reports serving on advisory boards, or consultancy, or speaker fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Medac, Novartis, Pfizer, Serac, and UCB. WT reports research grants from AbbVie, Celgene, Janssen, and Lilly; and consultancy or speaker fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, and UCB. M-AD reports serving on advisory boards, or consultancy, or speaker fees from AbbVie, BMS, Janssen, and Novartis. PR reports consulting fees from Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, and Pfizer; speakers bureau fees from Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, and Pfizer; and research grants from Janssen and Novartis. FB reports research grants from Celgene, Chugai, Janssen, Pfizer, and Roche; and personal fees from AbbVie, Boehringer, Celgene, Chugai, Genzyme, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi. ELM-B, XB, LC, and MK are full-time employees of AbbVie and might own stock or stock options. PGC reports serving as a consultant or on speaker bureaus for AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, GlaxoSmithKline, Novartis, and Pfizer. PM reports research grants and consultation or speaker honoraria from AbbVie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess whether tocilizumab treatment is associated with changes in depression symptoms in patients with rheumatoid arthritis (RA) during routine daily care., Methods: We retrospectively analysed data from a German non-interventional study (ARATA) of adult, tocilizumab-naïve RA patients who initiated subcutaneous tocilizumab and were followed for 52 weeks. The Beck Depression Inventory II (BDI-II) was used to assess symptoms of depression and create baseline subgroups of no (BDI-II<14), mild (14-19), moderate (20-28), and severe (≥29) depression. Other key outcomes included Disease Activity Score-28 joints (DAS28), patient-reported outcomes (PROs), and adverse events. Mixed model repeated measures (MMRM) assessed the impact of DAS28 on BDI-II over time, and Pearson correlation analyses evaluated associations between changes from baseline., Results: Of 474/1155 ARATA patients who completed the BDI-II at baseline, 47.7% had evidence of depression: 18.4% mild, 17.7% moderate, and 11.6% severe. 229 patients (48.3%) completed the BDI-II at both baseline and week 52. Two-thirds of patients with moderate or severe depression at baseline improved to a milder or no depression subgroup at week 52 (44/65 [67.7%]). Improvements in disease activity and PROs were observed in all subgroups, but patients with depression had lower response and higher adverse events rates. We observed an association between DAS28 and BDI-II over time in MMRM analyses, but the Pearson correlation for change from baseline was weak (r=0.10)., Conclusions: Depression is common in patients receiving routine care for RA. Improvements in depressive symptoms in RA during tocilizumab therapy appear to be distinct from changes in disease activity.

Objective: To evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD)., Methods: In the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing., Results: At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug)., Conclusions: Risankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD., Trial Registration Number: NCT03675308., Competing Interests: Competing interests: LEK has received honoraria or fees for serving as a speaker or consultant from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. He has received investigator-initiated study grants from AbbVie, Biogen, Janssen, Lilly, Novartis, Pfizer and UCB. MK has received honoraria or fees for serving on advisory boards, as a speaker or as a consultant, and has received grants as a principal investigator from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche and UCB. KP has received honoraria or fees for serving on advisory boards, as a speaker and as a consultant, as well as grants as principal investigator from AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda and UCB. LM has received fees for serving on an advisory board from Lilly. DW has received honoraria or fees for serving on advisory boards, as a speaker and as a consultant, from AbbVie and Novartis. WL, ZW, AMS, AE and LB are full-time employees of AbbVie and may hold AbbVie stock or stock options. AMS is listed as an inventor on some AbbVie patents. FB has received research grants, honoraria or fees for serving as a consultant or speaker from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche and Sanofi., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To characterize treatment patterns for patients with psoriatic arthritis (PsA) currently receiving any disease-modifying antirheumatic drug (DMARD)., Methods: The Strategy for Psoriatic Arthritis In Germany (SPAIG) study was a retrospective observational study conducted from May to November 2017 at 46 rheumatology centers. Current and previous treatment data were collected at a single visit from adult patients with PsA and psoriasis who received DMARD treatment for ≥6 of the previous 12 months. The primary outcome was the proportion of patients receiving a biologic DMARD (bDMARD). Multinomial logistic regression analysis was used to evaluate associations between current characteristics and initial choice of therapy., Results: Mean age of the 316 patients was 55.1 years and mean PsA disease duration was 9.9 years. PsA activity was generally comparable across treatment groups. In this cohort, 57.3% of patients were currently treated with bDMARDs, 37.7% with conventional synthetic DMARDs, and 4.4% with targeted synthetic DMARDs. Almost half (48.4%) of patients reported DMARD modifications in the previous 12 months. Specific comorbidities and patient/disease characteristics were associated with initial therapy., Conclusion: DMARD treatment of PsA is frequently modified, suggesting the need for more effective therapies and assessment tools., (© 2020 Japan College of Rheumatology.)

Introduction: Improvements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA)., Objective: These post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study., Methods: Patients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes., Results: Patients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points., Conclusion: High levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity. Trial registration NCT03151551 Key Points • Treatment goals for patients with psoriatic arthritis emphasise the importance of improving both musculoskeletal and non-musculoskeletal manifestations of the disease. • A combined endpoint considering both these manifestations, achievement of at least 50% improvement in American College of Rheumatology criteria and 100% improvement in Psoriasis Area Severity Index, was linked with achievement of a number of other endpoints relevant to psoriatic arthritis, including health-related quality of life that are important to patients with psoriatic arthritis. • Patients meeting the combined endpoint were more likely to achieve a disease state of remission, which is the stated aim of treatment for psoriasis., (© 2021. The Author(s).)

Objective: To investigate the efficacy and safety of rituximab + LEF in patients with RA., Methods: In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators' control., Results: Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders., Conclusion: The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring., Trial Registration: EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Moderate to severe plaque psoriasis can be treated effectively with immunomodulating biologicals such as the interleukin-17A inhibitor secukinumab. In practice, however, questions often arise as to how to proceed in special situations, such as infections, comorbidity, pregnancy, or surgery., Objectives: To address frequent questions about the treatment of plaque psoriasis with secukinumab in a consensus document of German psoriasis experts that supplements current guidelines., Methods: In a virtual expert meeting in May 2020, practical aspects of the treatment of psoriasis were discussed based on the experience of the participants and on current literature. The results of this discussion were summarized in the present consensus document., Results: This article provides practical guidance on case history, documentation of previous therapies, severity of psoriasis, and comorbidities before starting therapy with secukinumab. For patients treated with secukinumab, the course of action in case of vaccinations, chronic or acute infections, surgical interventions, special manifestations of psoriasis, and comorbidities including history of cancer and autoimmune disorders is discussed. Questions regarding family planning and health policy regulations are also addressed., Discussion: The recommendations for the treatment of psoriasis with secukinumab summarized in this consensus document may contribute to achieve optimal therapy for patients and to improve their quality of life., (© 2021. The Author(s).)

This paper deals with the problem of control through a semi-reliable communication channel, such as wireless sensor networks (WSN). Particularly, the case investigated is the one where the packet loss rate of the network is time-varying due to, for instance, variation in the distance between the nodes. Considering this practical motivation, the control system is modeled using a formulation based on discrete-time Markov jump linear systems (MJLS) with non-homogeneous Markov chains (time-varying transition probabilities). New control design conditions based on parameter-dependent linear matrix inequalities are proposed in order to solve this problem. The purpose is to demonstrate that this strategy is suitable to handle the networked control problem by comparing the temporal behavior of the closed-loop system with the Markovian controller and a standard proportional-integral-derivative (PID) controller. The case study presented in the paper considers the problem of the remote control of a Vertical Take-Off and Landing (VTOL) vehicle through a wireless communication channel. The network packet loss model employed in the case study is based on data collected on a wireless network workbench, which was previously developed and validated by the authors.