Development of Extramusculoskeletal Manifestations in Upadacitinib-Treated Patients With Psoriatic Arthritis or Axial Spondyloarthritis

Abstract

Objective: To assess the development of extramusculoskeletal manifestations (EMMs) among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) treated with upadacitinib 15 mg.

Methods: Data (cutoff: August 15, 2022) from five clinical trials in PsA (2), radiographic axSpA (r-axSpA; previously ankylosing spondylitis) (2), and nonradiographic axSpA (nr-axSpA) (1) were analyzed. Treatment-emergent adverse events of EMMs including uveitis, inflammatory bowel disease (IBD), and psoriasis were assessed in patients treated with placebo, upadacitinib 15 mg, or adalimumab (PsA only) and are reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]).

Results: Most patients (87.1%-99.3%) did not have a history of EMMs at baseline. In PsA, development of uveitis and IBD were low regardless of treatment or prior EMM history; rates were similar with upadacitinib 15 mg and adalimumab. In r-axSpA, development of uveitis was numerically lower (E/100 PY) in patients treated with upadacitinib 15 mg (2.8) versus placebo (7.5) and in patients with no history of uveitis (upadacitinib 15 mg 0.6; placebo 1.2) versus a history of uveitis (upadacitinib 15 mg 2.1; placebo 6.2); occurrence of IBD and psoriasis were low regardless of treatment or history. In nr-axSpA, development of uveitis was low regardless of history but was numerically lower in patients treated with upadacitinib 15 mg (0.9) versus placebo (2.1); occurrence of IBD and psoriasis were low or absent.

Conclusion: In patients with spondyloarthritis, development of EMMs was generally low with upadacitinib 15 mg. Uveitis was numerically lower in patients treated with upadacitinib 15 mg versus placebo, and particularly in r-axSpA. Regardless of treatment in r-axSpA, having a history of uveitis appeared to predispose patients for future uveitis events.

Figure 1

Development of uveitis in patients treated with upadacitinib across PsA, r‐axSpA, and nr‐axSpA. Development of uveitis in (A) PsA, (B) r‐axSpA, and (C) nr‐axSpA, stratified by history. EMM subtypes in PsA (E/100 PY [95% CI] [E]): anterior uveitis (including iritis and iridocyclitis) in PBO (0), UPA 15 mg (0.1 [0.0–0.4] [3]), and ADA (0); uveitis, not otherwise specified in PBO (0.7 [0.1–2.7] [2]), UPA 15 mg (< 0.1 [0.0–0.2] [1]), and ADA (< 0.1 [0.0–0.5] [1]). EMM subtypes in r‐axSpA: anterior uveitis in PBO (5.0 [1.4–12.8] [4]) and UPA 15 mg (2.0 [1.2–3.2] [19]); uveitis, not otherwise specified in PBO (2.5 [0.3–9.0] [2]) and UPA 15 mg (0.7 [0.3–1.5] [7]). EMM subtypes in nr‐axSpA: anterior uveitis in PBO (1.4 [0.2–5.2] [2]) and UPA 15 mg (0.9 [0.2–2.7] [3]); uveitis, not otherwise specified in PBO (0.7 [0.0–4.0] [1]) and UPA 15 mg (0). ^aAny exposure to UPA, including patients who switched from PBO to UPA 15 mg. ADA, adalimumab; CI, confidence interval; E/100 PY, events per 100 patient‐years; E, event; EAER, exposure‐adjusted event rate; EMM, extramusculoskeletal manifestation; EOW, every other week; NOS, not otherwise specified; nr‐axSpA, nonradiographic axial spondyloarthritis; PBO, placebo; PsA, psoriatic arthritis; PY, patient‐year; QD, once daily; r‐axSpA, radiographic axial spondyloarthritis; UPA, upadacitinib.

Figure 2

Development of IBD in patients treated with upadacitinib across PsA, r‐axSpA, and nr‐axSpA. Development of IBD in (A) PsA, (B) r‐axSpA, and (C) nr‐axSpA stratified by history. EMM subtypes in PsA (E/100 PY [95% CI] [E]): Crohn's disease in PBO (0.4 [0.0–2.1] [1]), UPA 15 mg (< 0.1 [0.0–0.2] [1]), and ADA (0); ulcerative colitis in PBO (0), UPA 15 mg (0), and ADA (0); colitis, not otherwise specified in PBO (0), UPA 15 mg (< 0.1 [0.0–0.3] [2]), and ADA (0). EMM subtypes in r‐axSpA: Crohn's disease in PBO (0) and UPA 15 mg (0.1 [0.0–0.6] [1]); ulcerative colitis in PBO (0) and UPA 15 mg (0); colitis, not otherwise specified in PBO (1.2 [0.0–6.9] [1]) and UPA 15 mg (0.1 [0.0–0.6] [1]). EMM subtypes in nr‐axSpA: Crohn's disease in PBO (0) and UPA 15 mg (0); ulcerative colitis in PBO (0) and UPA 15 mg (0.3 [0.0–1.7] [1]); colitis, not otherwise specified in PBO (0) and UPA 15 mg (0). ^aAny exposure to UPA, including patients who switched from PBO to UPA 15 mg. ADA, adalimumab; CI, confidence interval; E/100 PY, events per 100 patient‐years; E, event; EAER, exposure‐adjusted event rate; EMM, extramusculoskeletal manifestation; EOW, every other week; IBD, inflammatory bowel disease; NOS, not otherwise specified; nr‐axSpA, nonradiographic axial spondyloarthritis; PBO, placebo; PsA, psoriatic arthritis; PY, patient‐year; QD, once daily; r‐axSpA, radiographic axial spondyloarthritis; UPA, upadacitinib.

Figure 3

Development of psoriasis in patients treated with upadacitinib across r‐axSpA and nr‐axSpA. Development of psoriasis in (A) r‐axSpA and (B) nr‐axSpA stratified by history. EMM subtypes in r‐axSpA (E/100 PY [95% CI] [E]): psoriasis in PBO (1.2 [0.0–6.9] [1]) and UPA 15 mg (0.4 [0.1–1.1] [4]). EMM subtypes in nr‐axSpA: psoriasis in PBO (0) and UPA 15 mg (0). ^aAny exposure to UPA, including patients who switched from PBO to UPA 15 mg. CI, confidence interval; E/100 PY, events per 100 patient‐years; E, event; EAER, exposure‐adjusted event rate; EMM, extramusculoskeletal manifestation; nr‐axSpA, nonradiographic axial spondyloarthritis; PBO, placebo; PY, patient‐year; QD, once daily; r‐axSpA, radiographic axial spondyloarthritis; UPA, upadacitinib.