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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 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.)

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.)

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.)

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.)

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.)

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: The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear., Methods: In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab., Results: A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P<0.001 for both upadacitinib doses vs. placebo), and 65.0% with adalimumab. The difference between groups for 15-mg upadacitinib as compared with adalimumab was 5.6 percentage points (95% confidence interval [CI], -0.6 to 11.8) and for 30-mg upadacitinib as compared with adalimumab was 13.5 percentage points (95% CI, 7.5 to 19.4). Both upadacitinib doses were noninferior to adalimumab for the ACR20 response at week 12; the 30-mg dose but not the 15-mg dose was superior to adalimumab. The incidence of adverse events through week 24 was 66.9% with 15-mg upadacitinib, 72.3% with 30-mg upadacitinib, 59.6% with placebo, and 64.8% with adalimumab. There were serious infections in 1.2%, 2.6%, 0.9%, and 0.7% of the patients, respectively. Hepatic disorders occurred in 9.1% of patients in the 15-mg upadacitinib group and 12.3% in the 30-mg upadacitinib group, but grade 3 increases in aminotransferase levels occurred in 2% of patients or fewer in all groups., Conclusions: The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo. (Funded by AbbVie; SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Inhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD)., Objective: To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial., Methods: Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2)., Results: At enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event., Conclusion: Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD., Competing Interests: Competing interests: CK has received personal advisory board and congress fees from Novartis, Pfizer, Roche and Sobi. FB has received grants from Abbvie, Pfizer, Roche, Chugai and Janssen, and consultant, speaker or advisory board fees from Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme and Lilly; Boehringer; and Sandoz. NB has received grants from Novartis and Sobi, and personal fees from Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim and Roche. JCH has received grants from Novartis, Roche and Celgene, and advisory board and speaker fees from Novartis, Roche, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim and Celgene. AR-R has received speaker fees from UCB, and advisory board and speaker fees from Novartis, Roche, Lilly, Pfizer, Abbvie, BMS, Janssen, Sanofi and Celgene. CS has received personal fees from Abbvie, Boehringer-Ingelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB and Toshiba. EF has received advisory board and speaker fees from Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD and Sanofi., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response., Methods: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080., Findings: Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator., Interpretation: Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis., Funding: Novartis Pharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Assessment of individual therapeutic responses provides valuable information concerning treatment benefits in individual patients. We evaluated individual therapeutic responses as determined by the Disease Activity Score-28 joints critical difference for improvement (DAS28-d crit ) in rheumatoid arthritis (RA) patients treated with intravenous tocilizumab or comparator anti-tumor necrosis factor (TNF) agents. The previously published DAS28-d crit value [DAS28 decrease (improvement) ≥ 1.8] was retrospectively applied to data from two studies of tocilizumab in RA, the 52-week ACT-iON observational study and the 24-week ADACTA randomized study. Data were compared within (not between) studies. DAS28 was calculated with erythrocyte sedimentation rate as the inflammatory marker. Stability of DAS28-d crit responses and European League Against Rheumatism (EULAR) good responses was determined by evaluating repeated responses at subsequent timepoints. A logistic regression model was used to calculate p values for differences in response rates between active agents. Patient-reported outcomes (PROs; pain, global health, function, and fatigue) in DAS28-d crit responder versus non-responder groups were compared with an ANCOVA model. DAS28-d crit individual response rates were 78.2% in tocilizumab-treated patients and 58.2% in anti-TNF-treated patients at week 52 in the ACT-ion study (p = 0.0001) and 90.1% versus 59.1% at week 24 in the ADACTA study (p < 0.0001). DAS28-d crit responses showed greater stability over time (up to 52 weeks) than EULAR good responses. For both active treatments, DAS28-d crit responses were associated with statistically significant improvements in mean PRO values compared with non-responders. The DAS28-d crit response criterion provides robust assessments of individual responses to RA therapy and may be useful for discriminating between active agents in clinical studies and guiding treat-to-target decisions in daily practice.

Most studies of methotrexate (MTX) in combination with tumor necrosis factor (TNF) inhibitors have focused on treatment-naive patients with early disease. The goal of this study was to evaluate whether previous biologic therapy influenced the impact of concomitant MTX in patients initiating treatment with adalimumab.We retrospectively analyzed data from 2 large noninterventional studies of German patients with active rheumatoid arthritis (RA) who initiated adalimumab therapy during routine clinical practice. Patients were seen between April 2004 and February 2013 for study 1 and between April 2003 and March 2013 for study 2. Key outcomes were Disease Activity Score-28 joints (DAS28), patient global assessment of health (PGA), and pain. Subgroup analyses by prior biologic treatment were performed on patients treated with continuous adalimumab monotherapy or adalimumab plus MTX for 12 months and 2-sample t tests were used to evaluate differences. We also assessed outcomes in subgroups in which MTX had been added or removed at 6 months and compared outcomes with 1-sample t tests.Of 2654 patients, 1911 (72%) were biologic naive and 743 (28%) had received prior biologic therapy, usually with a TNF inhibitor. All subgroups showed improvements following initiation of adalimumab therapy. In patients with no previous biologic treatment, continuous adalimumab plus MTX was associated with greater improvements in DAS28, PGA, and pain at month 12 compared with continuous adalimumab monotherapy (P = .0006, .0031, and .0032, respectively). In patients with previous biologic treatment, concomitant MTX was associated with statistically significant benefits in pain only. Adding MTX at month 6 resulted in additional benefits in patients with no prior biologic therapy, but not those with previous biologics.We conclude that concomitant MTX resulted in additional improvements in DAS28 and PGA vs adalimumab monotherapy in patients with no previous biologic therapy, but changes were not statistically significant in patients treated with prior biologics. These findings may help inform the patient/provider treatment decision during routine clinical care.

Objectives: To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs)., Methods: Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24., Results: The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients., Conclusions: IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles., Competing Interests: Competing interests: PJM reports research grants and personal fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen and Lilly; and personal fees from Boehringer Ingelheim, Galapagos, Genentech and Gilead. JSS reports research grants from AbbVie, Astra-Zeneca, Janssen, Lilly, MSD, Novartis, Pfizer and Roche; and personal fees from AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB. FB reports research grants from Pfizer, Janssen, Chugai, Celgene and Roche; personal fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai; and investigator fees from Lilly. PN reports research grants and personal fees from AbbVie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Celgene, Gilead, Sanofi, UCB and Roche. HT reports research grants and non-financial support from Lilly. MG reports personal fees from AbbVie, Actelion Pharmaceuticals, Akros Pharma Inc, AMGEN Inc, Arcutis Pharmaceuticals Inc, Boehringer Engelheim International GmbH, Bristol-Myers Squibb Company, Celgene corporation, Dermira Inc, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Jannsen Inc, LEO Pharma, MedImmune, Merck and Co, Novartis Pharmaceuticals, Pfizer Inc, Regeneron Pharmaceuticals Inc, Roche Laboratories, Sanofi Genzyme, UCB and Valeant Pharmaceuticals Inc. PE has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly; has received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche and UCB; and has received research grants paid to his employer from AbbVie, BMS, Pfizer, MSD and Roche. PSH reports research grants, personal fees and non-financial support from AbbVie; research grants from Amgen, Janssen, Pfizer and UCB; and personal fees from Lilly and Galapagos. SLL, LL, EK, HL-S and SP are employees of, and own stock in, Eli Lilly and Company., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the long-term safety and efficacy of ixekizumab, an IL-17A antagonist, in patients with active PsA., Methods: In SPIRIT-P2 (NCT02349295), patients (n = 363) with previous inadequate response to TNF inhibitors entered the double-blind period (weeks 0-24) and received placebo or ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) following a 160-mg starting dose at week 0. During the extension period (weeks 24-156), patients maintained their original ixekizumab dose, and placebo patients received IXEQ4W or IXEQ2W (1:1). We present the accumulated safety findings (week 24 up to 156) at the time of this analysis for patients who entered the extension period (n = 310). Exposure-adjusted incidence rates (IRs) per 100 patient years are presented. ACR responses are presented on an intent-to-treat basis using non-responder imputation up to week 52., Results: From week 24 up to 156 (with 228 patient years of ixekizumab exposure), 140 [61.3 IR] and 15 (6.6 IR) patients reported infections and serious adverse events, respectively. Serious adverse events included one death and four serious infections. In all patients initially treated with IXEQ4W and IXEQ2W at week 0 (non-responder imputation), ACR20 (61 and 51%), ACR50 (42 and 33%) and ACR70 (26 and 18%) responses persisted out to week 52. Placebo patients re-randomized to ixekizumab demonstrated efficacy as measured by ACR responses at week 52., Conclusion: During the extension period, the overall safety profile of ixekizumab remained consistent with that observed with the double-blind period, and clinical improvements persisted up to 1 year.

Objective: To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously., Methods: A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary., Results: Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group., Conclusion: While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

Objective: To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX)., Methods: 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48., Results: At week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation., Conclusion: Treatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified., Trial Registration Number: NCT01999192; Results., Competing Interests: Competing interests: RFvV has received research support and grants from AbbVie, BMS, GSK, Pfizer and UCB and has been a consultant and received honoraria from AbbVie, AstraZeneca, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. ECK has received research funding from Abbott Laboratories, Amgen, AstraZeneca, BMS, Roche, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis and UCB; has served as a consultant/advisory board member for Abbott Laboratories, AstraZeneca, Biotest, BMS, Crescendo, Roche, Genentech, Janssen, Lilly, Merck, Pfizer, and UCB; and has received speaker honoraria from Amgen, Abbott Laboratories, Astrazeneca, BMS Canada, Roche, Janssen, Pfizer, Sanofi Genzyme, and UCB. VS has been a consultant for Biotest. CP-T has received support from Abbvie, BMS, Roche, UCB, Janssen, Amgen, AstraZeneca, Pfizer, GSK, Ely Lilly, Sanofi, Celltrion, Vertex and Novo-Nordisk. FB has received research grants/support from Roche, Pfizer and Chugai and has been a consultant for AbbVie, Biotest, BMS, Janssen, Lilly, Pfizer, UCB, Novartis, Genzyme, AstraZeneca, MSD/Merck. DZ, FR, RW, LK, RS, XZ, SA, BD and AW-D are or were employees of Biotest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

As in other inflammatory rheumatic diseases, the objective of psoriatic arthritis (PsA) treatment is the achievement of a defined target. Recent recommendations propose aiming for remission or low disease activity; however, a consensual definition of remission is lacking. A state of minimal disease activity (MDA) has been established and is defined by low activity assessed by tender/swollen joint counts, tender entheseal points, Psoriasis Area and Severity Index or body surface area, patient pain and global activity visual analog scale, and functional evaluation by Health Assessment Questionnaire. Since its development, MDA has been used increasingly in studies and clinical trials. In this article, the potential use of MDA as a treatment target in PsA is reviewed. The frequencies of MDA achievement with biologic disease-modifying antirheumatic drugs are summarized based on data from registries, observational studies, and clinical trials. Predictors and the prognostic effect of attaining MDA are also evaluated.

Current EULAR guidelines state that biologic DMARD (bDMARD) therapy should be administered in combination with MTX or other conventional synthetic (cs) DMARD in RA. Nonetheless, a third of patients for whom a bDMARD agent is prescribed take it in the absence of concurrent csDMARD therapy. While the reasons underlying the low uptake of bDMARD-csDMARD combination therapy in clinical practice have not been well delineated, they may include poor adherence, contraindication to csDMARD therapy and adverse effects, as well as csDMARD withdrawal following remission. The challenges surrounding bDMARD therapy and the benefit/risk ratio of biologic monotherapy when compared with combination with a csDMARD will be discussed. We will provide insights into these important issues, as well as reviewing the evidence base differentiating biologic agents and exploring therapeutic options for patients with rheumatoid arthritis for whom csDMARD therapy is contraindicated or discontinued., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To use statistical methods to establish a threshold for individual response in patient-reported outcomes (PROs) in patients with rheumatoid arthritis., Methods: We used an analysis of variance model in patients on stable therapy (discovery cohort) to establish critical differences (d crit ) for the minimum change associated with a significant individual patient response (beyond normal variation) in the PRO measures of pain (0-10), fatigue (0-10), and function (Funktionsfragebogen Hannover questionnaire; 0-100). We then evaluated PRO responses in patients initiating adalimumab in a noninterventional study (treatment cohort)., Results: In the discovery cohort (n = 700), PROs showed excellent long-term retest reliability. The minimum change that exceeded random fluctuation was conservatively determined to be 3 points for pain, 4 points for fatigue, and 16 points for function. In the treatment cohort (n = 2,788), 1,483 patients (53.2%) achieved a significant individual therapeutic response as assessed by Disease Activity Score in 28 joints (DAS28)-d crit (≥1.8 points) after 12 months of adalimumab treatment; 68.5% of patients with a DAS28-d crit response achieved a significant improvement in pain, whereas approximately 40% achieved significant improvements in fatigue or function. Significant improvements in all 3 PROs occurred in 22.7% of patients; 22.8% did not have any significant PRO responses. In contrast, significant improvements in all 3 PROs occurred in only 4.4% of 1,305 patients who did not achieve a DAS28-d crit response at month 12, and 59.1% did not achieve any significant PRO responses., Conclusion: The establishment of critical differences in PROs distinguishes true responses from random variation and provides insights into appropriate patient management., (© 2016, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objective: To evaluate the clinical/functional outcomes associated with etanercept (ETN) monotherapy versus combination therapy in psoriatic arthritis (PsA)., Methods: Data from patients with PsA who received ETN alone (n = 322) or combined with methotrexate (MTX; n = 152) for 24 weeks in 2 placebo-controlled clinical trials were summarized across studies., Results: Similar proportions of patients in the monotherapy and combination therapy groups achieved the PsA Response Criteria (80% and 83%) and the American College of Rheumatology improvements of 20% (ACR20; both 70%); numerically higher proportions receiving monotherapy achieved ACR50 (55% vs 48%) and ACR70 (35% vs 27%). Little between-group difference was observed in the 28-joint Disease Activity Score with C-reactive protein, the Psoriasis Area and Severity Index, and the Health Assessment Questionnaire-Disability Index improvement., Conclusion: ETN with and without MTX provided similar benefits in active PsA.

Objective: To examine the influence of concomitant methotrexate (MTX) with adalimumab (ADA) on outcomes in patients with psoriatic arthritis (PsA) using data from an observational study of ADA., Methods: Data from a German noninterventional study of patients with PsA starting treatment with ADA were analyzed retrospectively for effects of concomitant MTX on key outcomes, including Disease Activity Score-28 joints, tender and swollen joint counts, skin assessments, and safety. Patients were categorized into those with symptoms of axial involvement and those with no symptoms of axial involvement as judged by the examining clinician., Results: A total of 1455 patients met the study criteria, 296 with axial involvement (ADA monotherapy = 165; plus MTX = 131) and 1159 with no axial involvement (ADA monotherapy = 658; plus MTX = 501). ADA, alone or combined with MTX, resulted in strong and comparable reductions in disease activity measures in patients with and those without axial disease over 24 months of therapy. In multiple regression analyses, concomitant MTX did not affect joint or skin outcomes in either the group with axial manifestations or the group without axial disease. Neither adverse event rates nor withdrawal rates were significantly influenced by concomitant MTX., Conclusion: ADA is an effective treatment option for patients with PsA with or without axial involvement. Compared with ADA monotherapy, the use of concomitant MTX with ADA does not improve articular or skin outcomes in patients with PsA regardless of axial symptoms., Trial Registration: Clinicaltrials.gov NCT01111240.

Objectives: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA)., Methods: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety., Results: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters., Conclusions: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases., Trial Registration Number: NCT01023256., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: The aim of this study is to use data from a non-interventional study of adalimumab in patients with rheumatoid arthritis (RA) during routine clinical practice to evaluate the impact of prior treatment with biologics on the effectiveness of current therapy., Methods: Efficacy parameters were evaluated for all patients with values at baseline and month 12. Subgroup analyses were performed on patients with 0, 1, or ≥2 prior biologic agents. Key outcome measures included Disease Activity Score- 28 joints (DAS28) and Funktionsfragebogen Hannover (FFbH) functional ability score., Results: A total of 4700 RA adalimumab-treated patients were included in this analysis. Baseline disease activity increased with an increasing number of prior biologic agents and therapeutic response diminished. After 12 months of adalimumab therapy, DAS28 and FFbH scores showed improvements in all groups, but the group with 0 prior biologic agents had the best outcomes, while the group with ≥2 prior biologic agents had the worst. Clinical response (EULAR and DAS28-dcrit) and remission rates showed a similar pattern. Nevertheless, 44% to 67% of patients treated with ≥2 prior biologic agents achieved a clinical response. Multiple regression analyses identified prior biologic therapy as a significant negative predictor for response to therapy., Conclusions: Treatment with adalimumab leads to decreases in disease activity and improvements in function. Improvements are most pronounced in patients with 0 or 1 prior biologic agent, but a substantial proportion of patients treated with ≥2 prior biologic agents experience significant benefit from adalimumab therapy.

Objectives: The aim of this study was to review the available evidence on TNF inhibitor monotherapy vs combination therapy with MTX in PsA., Methods: A literature search was conducted up to and including October 2013 for randomized controlled trials (RCTs) and observational studies comparing TNF inhibitor monotherapy vs combination therapy with MTX in patients with PsA. Key information was extracted from the abstracts and/or full text of the articles retrieved., Results: Eleven published articles and three conference abstracts were retrieved, reporting on six RCTs of four TNF inhibitors. Most RCTs found no differences in efficacy for peripheral arthritis between patients treated with or without MTX. However, the studies were not powered to answer this question. Some data suggest that concomitant MTX may reduce the progression of structural damage. No significant differences in other outcomes have been reported. Data on TNF inhibitor monotherapy vs MTX combination therapy were reported from six registries. Three registries reported that the use of concomitant MTX did not affect the efficacy of TNF inhibitor therapy. Data from three European Union registries suggest that TNF inhibitor (especially mAbs) drug survival is superior in patients taking concomitant MTX, while one Canadian registry reported no difference., Conclusion: Available evidence on the efficacy and safety of TNF inhibitor monotherapy vs add-on MTX therapy shows little or no improvement with combination therapy, although the use of concomitant MTX appears to prolong TNF inhibitor drug survival of mAb TNF inhibitors. Registries and observational studies have the potential to fill some of the knowledge gaps in this area., (© The Author 2014. 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 association between skin and joint manifestations in patients with psoriatic arthritis (PsA) requires further characterization., Objective: We evaluated the association between severity of skin disease and joint involvement and the effectiveness and safety of adalimumab in PsA patients by baseline psoriasis severity., Methods: Descriptive statistics and regression analyses were used to evaluate data from 1,918 PsA patients starting adalimumab treatment. Subgroup analyses were conducted on patients empirically grouped by baseline target lesion score as a marker of psoriasis severity., Results: Psoriasis severity was not associated with joint manifestations at baseline or after 12 months of treatment. All subgroups showed improvements in skin and joints during therapy, and adalimumab was safe and well tolerated in all subgroups., Conclusion: The severity of skin manifestations does not correlate with the severity of joint disease in PsA patients; even patients with mild skin disease may have extensive musculoskeletal involvement.

Objective: To define a valid criterion for treatment response as assessed by the Disease Activity Score in 28 joints (DAS28) that exceeds random disease activity variations in patients with rheumatoid arthritis (RA)., Methods: We utilized anonymized data sets of RA patients from multiple rheumatology centers in Germany to identify patients with stable responses to conventional or biologic disease-modifying antirheumatic drug (DMARD) therapy (discovery cohort). To evaluate fluctuations in DAS28 scores, we subjected patients' DAS28 scores at months 12, 18, and 24 to an analysis of variance model to establish a 1-sided 95% confidence interval for normal fluctuations; this value was used to define the critical difference (DAS28-dcrit ) for individual changes from baseline. The DAS28-dcrit value was then applied to analyses of therapeutic response in an adalimumab noninterventional study cohort., Results: The discovery cohort included 415 patients receiving stable treatment. Values for DAS28-dcrit were comparable regardless of age, sex, disease activity, and class of therapy (DMARDs or biologic agents) and fell below 1.8 in all subgroups. We therefore conclude that DAS28 improvements of 1.8 or higher are outside the normal variation and represent a therapeutic response. When applied to data from the adalimumab noninterventional study (n = 1,874), a DAS28-dcrit response was more robust over time than a European League Against Rheumatism response and was more closely correlated with improved functional capacity., Conclusion: Based on our data, a DAS28-dcrit value of 1.8 signifies a positive individual therapeutic response that exceeds the threshold of random fluctuation. The DAS28-dcrit criterion may be useful in steering individual therapy and stratifying clinical trials., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To determine the "real-world" clinical effectiveness and safety of leflunomide in patients with psoriatic arthritis (PsA)., Methods: This prospective, multinational 24-week observational study involved adult patients with active PsA who initiated treatment with leflunomide. Patients were evaluated at baseline, 12 weeks, and 24 weeks. The primary outcome was response as assessed by the Psoriatic Arthritis Response Criteria (PsARC) in patients with pre- and posttreatment data. A modified PsARC response analysis included patients with joint counts, but no severity scores. Other effectiveness evaluations included global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. All patients were evaluated for safety., Results: A total of 514 patients were enrolled in this study (mean age 50.7 years, mean disease duration 6.1 years). In the primary effectiveness analysis, 380 (86.4%) of 440 patients (95% confidence interval 82.8%-89.4%) achieved a PsARC response at 24 weeks. Significant improvements were observed in tender and swollen joint scores and counts, patient and physician global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. The discontinuation rate was 12.3%. Ninety-eight adverse drug reactions occurred in 62 (12.1%) patients; 3 drug reactions were serious (2 increased liver enzymes, 1 hypertensive crisis)., Conclusion: Leflunomide is an effective and well-tolerated option for PsA in daily clinical practice, with beneficial effects on peripheral arthritis and on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease., (Copyright © 2013 by the American College of Rheumatology.)

Purpose of Review: Leflunomide is often used as a first choice disease-modifying antirheumatic drug after methotrexate. New data are available for efficacy and safety in both, monotherapy and combination with biologicals., Recent Findings: New data on efficacy demonstrate comparable effect sizes for leflunomide and methotrexate in the treatment of signs and symptoms in combination with tumour necrosis factor-blocking agents and rituximab. Equipotency has also been demonstrated by a recent radiographic outcome study on methotrexate and leflunomide monotherapy. Pharmacogenetic studies indicate an impact of polymorphisms on the variability in serum levels of the compound with potential relevance to effectiveness and tolerability in individual patients. Genetic factors are also likely to contribute to the significantly increased risk for leflunomide-induced pulmonary disease reported in Asia. Because pre-existing interstitial lung disease as well as methotrexate-induced pneumonitis have been identified as risk factors for leflunomide-induced pulmonary disease, the use of leflunomide as an alternative to methotrexate is limited under these conditions., Summary: Effectiveness of leflunomide renders it a potent treatment option in rheumatoid arthritis. The known tolerability issues resulting in a less favourable adherence to therapy constitutes a weakness. However, documented data from large registries indicate that leflunomide is safe as far as the contraindications and recommendations for monitoring are regarded.

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. Plain Language Summary: Psoriatic arthritis (PsA) often affects individuals with the skin condition psoriasis. A biologic disease-modifying antirheumatic drug can help control inflammation and regulate the immune system to ease symptoms and slow progression of PsA. The ongoing KEEPsAKE 1 study is evaluating the efficacy and safety of risankizumab in patients with active PsA who previously have not had success with ≥ 1 conventional disease-modifying antirheumatic drug. Patients were initially treated with risankizumab 150 mg (continuous risankizumab group) or inactive drug (inactive drug/risankizumab group). After 24 weeks, all received risankizumab for the rest of the study. At week 100, 64% (continuous risankizumab group) and 62% (inactive drug/risankizumab group) of patients had ≥ 20% improvement in PsA symptoms (measured using American College of Rheumatology [ACR20] criteria). Both groups showed similar percentages at week 52 and improvement from week 24. In patients who achieved ACR20 at week 52, 81% maintained their ACR20 response at week 100. Minimal disease activity was defined as a combination of joint and skin symptoms, affected body surface area, pain, and physical functioning. At week 100, 38% of the continuous risankizumab group and 35% of the inactive drug/risankizumab group achieved minimal disease activity. Percentages were similar at week 52 and higher than week 24 in both groups. In patients who achieved minimal disease activity at week 52, 81% maintained response at week 100. All other measures of treatment responses showed similar patterns from the start of risankizumab through week 100. Risankizumab was considered generally safe by the treating physicians. [ABSTRACT FROM AUTHOR]

Background: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors.Methods: In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis.Results: At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib.Conclusions: In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .). [ABSTRACT FROM AUTHOR]