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Objectives: This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA)., Methods: This evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs. For observational studies, a random-effects model was used to pool rate ratios (RRs)., Results: ~49 000 patients receiving abatacept were analysed from clinical trials (~7000) and observational studies (~42 000). In randomised trials (n=4138; median abatacept exposure, 12 (range 2-30) months), NMSC IRs (95% CIs) were not significantly different for abatacept (6.0 (3.3 to 10.0)) and placebo (4.0 (1.3 to 9.3)) and remained stable throughout the long-term, open-label period (median cumulative exposure, 28 (range 2-130 months); 21 335 p-y of exposure (7044 patients over 3 years)). For registry databases, NMSC IRs/1000 p-y were 5-12 (abatacept), 1.6-10 (csDMARDs) and 3-8 (other b/tsDMARDs). Claims database IRs were 19-22 (abatacept), 15-18 (csDMARDs) and 14-17 (other b/tsDMARDs). Pooled RRs (95% CIs) from observational studies for NMSC in patients receiving abatacept were 1.84 (1.00 to 3.37) vs csDMARDs and 1.11 (0.98 to 1.26) vs other b/tsDMARDs., Conclusions: Consistent with the warnings and precautions of the abatacept label, this analysis suggests a potential increase in NMSC risk with abatacept use compared with csDMARDs. No significant increase was observed compared with b/tsDMARDs, but the lower limit of the 95% CI was close to unity., Competing Interests: Competing interests: TS was an employee of and shareholder in Bristol Myers Squibb (at the time of the analysis; former employee at present). LD, VK, AD and MAM are employees of and shareholders in Bristol Myers Squibb. SS reports advisory board involvement, speaker fees and grant/research support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novartis. KM reports grant/research support from Rheumatology Research Foundation. MH is an employee of the University of Maryland School of Medicine (full time) and US Department of Veterans Affairs (part time); reports consultancy fees and advisory board involvement from Bristol Myers Squibb, Eli Lilly, Kolon TissueGene, Inc, Novartis, Pfizer, Samumed and Theralogix; is a member of the Data Safety Monitoring Committee for Galapagos, Roche, and IQVIA; reports royalties from Elsevier and UpToDate; reports stock ownership in BriOri Biotech and Theralogix; and is president of Rheumcon. MB reports consultancy fees from Novartis. JA reports grant/research support from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB for ARTIS. AS reports speaker fees from AbbVie, Bristol Myers Squibb, Celltrion, Lilly, Merck, Pfizer and Roche., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment., Methods: This post hoc analysis used baseline peripheral whole blood transcriptomic data from patients in a phase IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were used with a published deconvolution algorithm to identify immune cell proportions in patient samples, and unsupervised consensus clustering was generated. Efficacy data were re-analysed., Results: Patient data (n=144: abatacept: n=98; placebo: n=46) were grouped into four main clusters (C) by predominant characteristic cells: C1-neutrophils; C2-cytotoxic T cells, B-cell receptor-ligated B cells, monocytes, IgG memory B cells, activated T helper cells; C3-plasma cells, activated dendritic cells, activated natural killer cells, neutrophils; C4-activated dendritic cells, cytotoxic T cells. C3 had the highest baseline total British Isles Lupus Assessment Group (BILAG) scores, highest antidouble-stranded DNA autoantibody levels and shortest time to flare (TTF), plus trends in favour of response to abatacept over placebo: adjusted mean difference in BILAG score over 1 year, -4.78 (95% CI -12.49 to 2.92); median TTF, 56 vs 6 days; greater normalisation of complement component 3 and 4 levels. Differential improvements with abatacept were not seen in other clusters, except for median TTF in C1 (201 vs 109 days)., Conclusions: Immune cell clustering segmented disease severity and responsiveness to abatacept. Definition of immune response cell types may inform design and interpretation of SLE trials and treatment decisions., Trial Registration Number: NCT00119678; results., Competing Interests: Competing interests: SB, SEC, OJ, SK, MAM and RMT are employees and shareholders of Bristol-Myers Squibb. JY is an employee of Bristol-Myers Squibb. RW has received grant/research support from Roche and UCB, is a consultant for Bristol-Myers Squibb, Galapagos and Janssen, and has participated in a speakers’ bureau for Bristol-Myers Squibb. PN has no conflicts of interest. JTM has received consulting fees from Abbott, Amgen, Astellas, Bristol-Myers Squibb, Cephalon, Eisai, EMD Serono, Genentech/Roche, Human Genome Sciences/GlaxoSmithKline, Lilly, MedImmune/AstraZeneca, Ono, Pfizer, Questcor, UCB, and research grants from Genentech/Roche, Pfizer and UCB.

Objectives: To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study., Methods: In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1-Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates., Results: Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1-Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group., Conclusions: In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab., Trial Registration Number: NCT00929864., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)