Background/Purpose: Despite advances in psoriatic arthritis (PsA) treatment, remission remains elusive for many patients. This has prompted growing interest in combining biologic and targeted synthetic DMARDs (b/tsDMARDs). However, real-world data on such combinations are limited. This case series evaluates clinical outcomes and safety of b/tsDMARD combinations in PsA patients.

Methods: Case series of PsA patients receiving combined b/tsDMARD therapy, including TNFi, JAKi, TYK2i, IL17i, IL23i, IL-12/23i for effectiveness and safety. Combinations with Apremilast (APR) were analyzed for safety. Clinical and safety data were prospectively collected using standardized instruments within a longitudinal PsA cohort, and supplemented via chart review. Effectiveness was assessed by changes in joint counts, DAPSA, PASI, BSA, and patient-reported outcomes (NRS for pain, skin, and global) at 3-6 and 6-12 months. Safety outcomes included infections and non-infectious adverse events (AEs).

Results: We identified 22 patients treated with bDMARDs + JAKi or TYK2i, some with multiple regimens. Eleven (50%) were female. Complete information on PsA measure of activity was available for 9 patients (Table 1), while 13 had partial data, including age, sex, skin activity, and AEs. Numerical improvements were observed across disease activity measures, with Figure 1 showing patients with visits in the prespecified timeframes, and Table 2 showing the safety data.In the bDMARD + JAKi group (n=6), IL17i + JAKi were the most frequent combinations (n=4), used for 4,145 days (11.35 patient-years [PY]). One case of mild infectious stomatitis was reported, but treatment was not discontinued. IL23i + JAKi (n=2), used for 1,337 days (3.7 PY), had no AEs. For the bDMARD + TYK2i group (n=19), IL-17i + TYK2i (n=9) were used for 3,229 days (8.5 PY). One patient experienced two mild upper respiratory infections (URIs) on bimekizumab and deucravacitinib, prompting a switch for risankizumab with deucravacitinib. IL-23i with TYK2i (n=10) were used for 3,325 days (9.1 PY), with two cases of mild URIs leading to a switch to bimekizumab monotherapy, and one case of folliculitis, where therapy was continued. One patient received TNFi + TYK2i for 324 days (0.9 PY), with no AEs. We identified 16 patients on bDMARDs + APR (total of 22 combinations, with a median duration of 825 days), including IL12/23i or IL23i + APR (8 combinations, duration: 360–2,250 days), IL17i + APR (8 combinations, duration: 90–2,790 days), TNFi + APR (5 combinations, duration: 180–2,340 days), and JAKi + APR (1 combination, 540 days). Two cases of diarrhea were observed, but no infections occurred.

Conclusion: Overall, the safety profile of bDMARD combinations with tsDMARDs was favorable. Infections, primarily URIs, were the most common AEs – mild in severity, non-hospitalized, and rarely requiring treatment change. Short-term improvements were observed in both musculoskeletal and skin domains. Our findings, drawn from a prospective cohort with standardized data collection, support the effectiveness and safety of combination therapy in selected PsA cases. Randomized controlled trials are needed to confirm long-term efficacy and safety.

Table 1. Demographics and clinical characteristics of patients on combined bDMARD and JAK/TYK2i.

Table 2. Safety analysis. IL17i, interleukin 17 inhibitor; tsDMARD, target-synthetic disease-modifying antirheumatic drug; IL23i, interleukin 23 inhibitor; TNFi, tumor necrosis factor inhibitor; IL12/23i, interleukin 12/23 inhibitor; JAKi, janus kinase inhibitor.

Figure 1. Individual trajectories after starting combined therapy for patients with follow-ups according to protocol.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/combination-of-biological-and-targeted-synthetic-disease-modifying-antirheumatic-drugs-in-psoriatic-arthritis-a-case-series/