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Background: The EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels., Objectives: This study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi., Methods: We performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected., Results: We included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months ( p  = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX ( p  = 0.09) or ADL ( p  = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP., Conclusion: Baseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP., Competing Interests: CP-R has received research grants/honoraria from AbbVie, Pfizer, Novartis, Lilly, and Roche. MN-N has received research grants/honoraria from Galápagos, Janssen, Lilly, Novartis, and UCB. AB received grant/research support and fees for consultancies or as a speaker from AbbVie, Amgen, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Plasencia-Rodríguez, Martínez-Feito, Novella-Navarro, Pérez De Diego, Bonilla, Gehin, Villalba-Yllán, Nuño, Pascual-Salcedo, Nozal, Almirón and Balsa.)

Background: A consensus definition for active sacroiliitis by MRI, mentioned in the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA), was published in 2009 and included a qualitative and quantitative MRI cut-off component. In 2021, updates to the quantitative component were preliminarily proposed. This post hoc analysis of part A of the phase 3 open-label C-OPTIMISE study (NCT02505542) explores the differences by applying the 2009 and preliminary 2021 inflammatory cut-offs on clinical outcomes of axSpA patients treated with certolizumab pegol., Methods: Baseline MRI scans were used to classify 657 patients as MRI+ or MRI- according to the quantitative components of the 2009 and preliminary 2021 MRI cut-offs for inflammatory lesions. Clinical outcomes, including ASAS ≥40% improvement (ASAS40), Ankylosing Spondylitis Disease Activity Score and Bath Ankylosing Spondylitis Disease Activity Index, were reported to week 48., Results: Across all analysed outcomes, 2009 MRI+ and preliminary 2021 MRI+ subgroups showed similar results. Notably, clinical outcomes for the discordant group (2009 MRI+but preliminary 2021 MRI- group; 53/657 [8.1%]) were close to those seen in MRI- patients according to either 2009 or preliminary 2021 inflammatory cut-offs, and notably different from the totality of MRI+ subgroups., Conclusion: This analysis suggests that the preliminary 2021 cut-offs for MRI inflammatory lesions may slightly increase the specificity of the quantitative part of the 2009 MRI inflammatory lesion definition. The effects of the updated MRI cut-offs need to be assessed on the basis of efficacy outcomes and with the inclusion of aspects of structural changes., Trial Registration Number: NCT02505542., Competing Interests: Competing interests: XB: Speakers’ bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma; Paid instructor for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma; Consultant of AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma. PMM: Personal fees from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB Pharma. LB, BH: Employee and stockholder of UCB Pharma. MK, TK: Employee of UCB Pharma. RT: Veramed statistical consultant for UCB Pharma. MR: Speakers’ bureau from: AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma; Consultant of AbbVie, Eli Lilly, Novartis, 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.)

Abstract Background Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP). Methods C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value

This article discusses the dosage and dosing of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA) in Japan. The recommended dose of MTX in Japan is lower than the global recommendation, with an initial dose of 8 mg/week and a maximum dose of 16 mg/week. Studies have shown that lower doses of MTX can be effective for Japanese patients with RA, and factors such as body mass index, pharmacogenomics, and the intestinal microbiome may contribute to the difference in optimal dosage between Japan and other countries. The article also discusses the use of divided dosing or subcutaneous injection to achieve lower gastrointestinal toxicity and higher bioavailability of MTX. However, it is important to note that dividing the dose into multiple intakes may increase the risk of medication errors. Further international studies are needed to understand the factors contributing to variations in the optimal use of MTX. [Extracted from the article]

This article, titled "PARADOXICAL SARCOIDOSIS CASE," discusses a case of paradoxical sarcoidosis in a 56-year-old female patient with ankylosing spondylitis who was receiving certolizumab treatment. After receiving five doses of certolizumab, the patient experienced weight loss, fatigue, loss of appetite, and widespread joint pain. Further examinations revealed lymphadenomegaly and granuloma, leading to a diagnosis of paradoxical sarcoidosis. The certolizumab treatment was discontinued, and the patient was monitored for improvement. The article emphasizes that such reactions tend to improve or resolve with the discontinuation of the medication. [Extracted from the article]

Introduction: We aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive. Methods: TNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay. Comparisons between nADAb-positive and -negative patients were done in unadjusted analyses as well as in adjusted logistic regression and general linear models. Results: A total of 282 patients with IA currently under treatment with TNFi were included. nADAb were identified in 11 patients (nine treated with infliximab, one with etanercept and one with certolizumab pegol). Patients with nADAb reported significantly worse joint pain, patient's global assessment, Health Assessment Questionnaire, Bath Ankylosing Spondylitis Disease Activity/Functional Index and Short-Form-36 physical functioning scale score than patients without nADAb (p < 0.04, adjusted analyses). 28-joint Disease Activity Score, Simplified Disease Activity Index and Maastricht Ankylosing Spondylitis Enthesitis score were also significantly worse in the nADAb-positive patients (p < 0.04, adjusted analyses), as were serum calprotectin, C-reactive protein and numbers of circulating peripheral leukocytes (p ≤ 0.001). A significantly higher proportion of nADAb-positive patients were current smokers (46 vs. 15%), in unadjusted as well as adjusted analyses (p ≤ 0.008). Conclusions: nADAb-positive patients were more frequently smokers and had significantly worse disease activity, physical function, and inflammatory markers, than patients without nADAb. The association between smoking and nADAb positivity warrants further examination. [ABSTRACT FROM AUTHOR]

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann–Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF1; RF 0–15.0 IU/mL, RF2; 15.0–55.0, RF3; 55.0–166, RF4; 166–7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc [3.2 (2.3–4.2) vs. 2.7 (2.0–3.0)] after 12 months. This effect of TNFi without Fc for the change of DAS28-ESR after 12 months treatment retained in multivariate analysis in RF4. TNFi without Fc may be more efficacious than TNFi with Fc in RA patients with high RF titres. [ABSTRACT FROM AUTHOR]

This review will summarize clinical, genetic, and pathophysiologic characteristics that are shared between children with enthesitis‐related arthritis (ERA) with axial involvement and adults with nonradiographic (and in some cases radiographic) axial spondyloarthritis (SpA), as well as between children with ERA and primarily peripheral disease manifestations and adults with peripheral SpA. Due to the differences in classification criteria for children with ERA and adults with axial and peripheral SpA, the US Food and Drug Administration (FDA) granted automatic full waivers of studies in children for new medications for "axial spondyloarthropathies including ankylosing spondylitis" up until July 2020. Thus, although current juvenile idiopathic arthritis treatment guidelines recommend the use of biologic disease‐modifying antirheumatic drugs as part of the early treatment for patients with ERA, none of the FDA‐approved therapies for peripheral SpA or nonradiographic axial SpA (certolizumab pegol, ixekizumab, and secukinumab) have been studied or are labeled for use in children with ERA. Considering the similarities between adult SpA and ERA in terms of etiology, genetics, pathogenesis, and clinical manifestations summarized in this review, medications approved for axial SpA or peripheral SpA should also be studied in children with active ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children. Considering the current lack of effective FDA‐approved therapies for ERA, the FDA should also consider requiring pediatric studies for medications that have already been approved for the treatment of adults with SpA. [ABSTRACT FROM AUTHOR]

Adalimumab (ADA), certolizumab pegol (CER), etanercept (ETA), guselkumab (GUS), ixekizumab (IXE), secukinumab (SEC), and ustekinumab (UST) are biologics approved for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA). We examined adherence and persistence among PsO patients with comorbid PsA who initiated treatment with any of these biologics. Adult patients with ≥1 pharmacy/medical claim for any of these seven biologics, and ≥1 diagnosis of both PsO and PsA were selected from the MarketScan Commercial database (July 2014–June 2019). Adherence and persistence rates were examined among the seven study cohorts during fixed follow-up periods (3, 6, 9, and 12 months). Among patients with ≥9 months of continuous enrollment, 3,251 initiated ADA, 418 CER, 1,563 ETA, 126 GUS, 422 IXE, 1,596 SEC, and 1,267 UST. During the 9-month follow-up period, the proportions of adherent patients were numerically highest among those treated with GUS (59.5%) and UST (57.0%), followed by SEC (47.9%), IXE (47.6%), ADA (46.8%), ETA (37.4%), and CER (22.0%); persistence rates were also numerically highest among those treated with GUS (65.9%) and UST (65.7%). Adjustment for potential confounders was not conducted. Adherence and persistence rates were numerically highest among patients who initiated GUS and UST. [ABSTRACT FROM AUTHOR]

Introduction: We report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217). Methods: Patients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved "much improved" or "very much improved" on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician's Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0–52. Results: Of 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response ("improved" or "remission"). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients. Conclusion: CZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified. Trial Registration: ClinicalTrials.gov identifier, NCT03051217. [ABSTRACT FROM AUTHOR]

Key messages: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1–2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients. [ABSTRACT FROM AUTHOR]

Patients requiring systemic therapies have extensive skin involvement, significant impact on functioning or QOL, and disease in sensitive areas and/or they are refractory to topical therapies. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: Findings from the National Psoriasis Foundation (NPF) surveys, 2003-2011. Narrowband UVB (NB-UVB) is the preferred phototherapy regimen for most patients with generalized psoriasis, whereas targeted phototherapy with an excimer laser is appropriate for patients with localized disease. ABBREVIATIONS IN THIS FEATURE AAD American Academy of Dermatology ACR American College of Rheumatology BAD British Association of Dermatologists BB-UVA Broadband UVA BSA Body surface area DLQI Dermatology Life Quality Index IBD Inflammatory bowel disease NB-UVB Narrowband UVB NPF National Psoriasis Foundation PASI Psoriasis Area Severity Index PGA Physician Global Assessment PsA Psoriatic arthritis PUVA Psoralen plus UVA QOL Quality of life TCI Topical calcineurin inhibitor TCS Topical corticosteroid TNF Tumor necrosis factor SESSION OVERVIEW PSAP in JACCP features are developed from activities presented as part of the Pharmacotherapy Self-Assessment Program (PSAP). [Extracted from the article]

The article reports that Tumor necrosis factor α (TNF-α) inhibitor–induced lupuslike syndrome (TAILS) is a newly described entity that refers to the onset of subacute cutaneous lupus erythematosus (SCLE) during drug therapy with TNF-α antagonists. The condition is unique because it is thought to occur via a separate pathophysiologic mechanism than all other agents implicated in the development of druginduced lupus erythematosus (DILE).

BackgroundAlthough one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsPatients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively.ResultsOverall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R 2 = 0.311, p = 0.013; R 2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R 2 = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R 2 = 0.558, p

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects apocrine gland-bearing skin. The management of HS with biologics has expanded significantly over the past few years. Certolizumab pegol is a pegylated (polyethylene glycol) antigen-binding fragment of a recombinant humanized anti-TNF-a monoclonal antibody, which is approved for psoriasis, rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. In recent years many reports have been merging on the use of certolizumab in treating hidradenitis suppurativa. The electronic database MEDLINE was searched through PubMed in February 2022 using the following search terms: Certolizumab "[All Fields] OR" certolizumab pegol"[All Fields] AND "Hidradenitis suppurativa"[ All Fields]. The search revealed that certolizumab was used in 6 case reports to treat HS with a total of 7 patients. We can conclude that there are few cases in the literature discussing the use of certolizumab in HS, all of which, show a good and promising response with no reported side effects. [ABSTRACT FROM AUTHOR]

The article discusses the Juvenile Spondyloarthritis Disease Activity Index (JSpADA), a disease activity index that was developed for the juvenile SpA population. The study examined an abbreviated version of the JSpADA by reviewing visits of patients with SpA captured in the Childhood Arthritis and Rheumatology Research Alliance Registry.