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Review
. 2024 Jan 11;83(2):177-183.
doi: 10.1136/ard-2023-224356.

Abatacept and non-melanoma skin cancer in patients with rheumatoid arthritis: a comprehensive evaluation of randomised controlled trials and observational studies

Teresa A Simon  1 , Lixian Dong  1 , Samy Suissa  2   3 , Kaleb Michaud  4   5 , Sofia Pedro  5 , Marc Hochberg  6 , Maarten Boers  7 , Johan Askling  8   9 , Thomas Frisell  9 , Anja Strangfeld  10   11 , Yvette Meissner  10 , Vadim Khaychuk  12 , Alyssa Dominique  1 , Michael A Maldonado  13
Affiliations
Review

Abatacept and non-melanoma skin cancer in patients with rheumatoid arthritis: a comprehensive evaluation of randomised controlled trials and observational studies

Teresa A Simon et al. Ann Rheum Dis. .

Abstract

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.

Keywords: abatacept; arthritis, rheumatoid; biological therapy; epidemiology.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Pooled analysis of NMSC RRs for abatacept versus csDMARDs. ARTIS was not included because the investigators did not provide a fully adjusted point estimate. MarketScan, Optum and PharMetrics did not run RRs for this comparison. A random-effects model was used to address heterogeneity. The RRs were calculated separately in each database and a pooled estimate was conducted. ARTIS, Anti-Rheumatic Therapy in Sweden; csDMARD, conventional synthetic disease-modifying antirheumatic drug; FORWARD, The National Databank for Rheumatic Diseases; NMSC, non-melanoma skin cancer; RABBIT, Rheumatoid Arthritis Observation of Biologic Therapy; RR, rate ratio.
Figure 2
Figure 2
Pooled analysis of NMSC RRs for abatacept versus other b/tsDMARDs. RABBIT did not run RRs for this comparison. A random-effects model was used to address heterogeneity. The RRs were calculated separately in each database and a pooled estimate was conducted. ARTIS, Anti-Rheumatic Therapy in Sweden; b/tsDMARD, biological/targeted synthetic disease-modifying antirheumatic drug; FORWARD, The National Databank for Rheumatic Diseases; MarketScan, Truven MarketScan Commercial and Supplemental Medicare; NMSC, non-melanoma skin cancer; Optum, Optum Clinformatics Data Mart; PharMetrics, IMS PharMetrics; RABBIT, Rheumatoid Arthritis Observation of Biologic Therapy; RR, rate ratio.
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