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Clinical Trial
. 2023 Feb;9(1):e002735.
doi: 10.1136/rmdopen-2022-002735.

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis

Gerd R Burmester  1 , Stanley B Cohen  2 , Kevin L Winthrop  3 , Peter Nash  4 , Alan D Irvine  5   6 , Atul Deodhar  3 , Eduardo Mysler  7 , Yoshiya Tanaka  8 , John Liu  9 , Ana P Lacerda  9 , Hannah Palac  9 , Tim Shaw  10 , Philip J Mease  11 , Emma Guttman-Yassky  12
Affiliations
Clinical Trial

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis

Gerd R Burmester et al. RMD Open. 2023 Feb.

Abstract

Objective: To evaluate the long-term safety profile for upadacitinib across rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and atopic dermatitis (AD).

Methods: Safety data from clinical trials of upadacitinib 15 mg and upadacitinib 30 mg (AD only) for treating RA, PsA, AS and AD as of 30 June 2021 were analysed; some RA and PsA studies included adalimumab and methotrexate as active comparators. Treatment-emergent adverse events (TEAEs) were presented by disease as exposure-adjusted event rates per 100 patient years (E/100 PY).

Results: The analysis included 6991 patients (RA, n=3209; PsA, n=907; AS, n=182; AD, n=2693) who received at least one dose of upadacitinib, representing 15 425 PY of exposure (maximum duration 2.75-5.45 years) across diseases. Rates (E/100 PY) of any TEAE (205.5-278.1) and TEAE leading to discontinuation (4.5-5.4) were similar across diseases; serious TEAEs were numerically higher in patients with RA and PsA. Rates of herpes zoster (1.6-3.6), non-melanoma skin cancer (0-0.8) and elevations in creatine phosphokinase levels (4.4-7.9) were higher with upadacitinib than with active comparators in the RA and PsA populations. Deaths (0-0.8), serious infections (0-3.9), major adverse cardiovascular events (0-0.4), venous thromboembolism (<0.1-0.4) and malignancies (0.3-1.4) were observed, with rates generally lowest in AS and AD. Increased rates of acne were observed in patients with AD only.

Conclusions: Findings from this analysis demonstrate that upadacitinib is generally well tolerated with observed differences in safety profiles likely reflective of varying patient characteristics across RA, PsA, AS and AD populations.

Trial registration numbers: NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT03569293, NCT03568318 and NCT03607422.

Keywords: Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Inflammation; Spondylitis, Ankylosing.

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Conflict of interest statement

Competing interests: GRB received consulting fees and honoraria for lectures from AbbVie, Eli Lilly, Gilead and Pfizer and is editor of RMD Open. SBC received grants and consultation fees from Amgen, AbbVie, Boehringer Ingelheim, Gilead, Pfizer, Roche and Sandoz. KLW received consulting fees and/or research grants from AbbVie, BMS, Lilly, Pfizer, Roche Gilead, Galapagos and UCB. PN received research grants and consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead and Janssen, and is a member of speakers’ bureaus for AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead and Janssen. ADI received honorarium for consultancy from AbbVie, Arena Pharmaceuticals, Aslan, BenevolentAI, Chugai, Dermavant, Genentech, LEO Pharma, Lilly, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi and UCB. AD received grant/research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and is a consultant for AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith Kline, Janssen, MoonLake, Novartis, Pfizer and UCB. EM received or has pending grants from Roche, Pfizer, Bristol-Myers Squibb and Novartis. He had received honorarium from Eli Lilly, Pfizer, GlaxoSmithKline, Roche, Sanofi, AstraZeneca, Sandoz, Amgen, Gemmene and AbbVie; provided writing assistance, medicines, equipment or administrative support to Pfizer, AbbVie and Roche; and received payment for lectures including service on speakers’ bureaus from Eli Lilly, Pfizer, GlaxoSmithKline, Roche, Sanofi, AstraZeneca, Sandoz, Amgen, Gema Biotech and AbbVie. YT received speaking fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers Squibb, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi Kasei, GlaxoSmithKline, Mitsubishi-Tanabe, Gilead and Janssen, and research grants from Mitsubishi-Tanabe, Chugai, AbbVie, Takeda, UCB, Daiichi-Sankyo and Eisai. PJM received grants/research support from AbbVie, Amgen, Bristol-Myers Squibb, Inmagene, Janssen, Eli Lilly, Novartis, Pfizer and UCB; is a consultant for AbbVie, Acelyrin, Aclaris, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, MoonLake, Novartis, Pfizer, Sun Pharma, INC Pharma and UCB; and is on speakers’ bureaus for AbbVie, Amgen, Janssen, Novartis, Pfizer, UCB and Crescendo Bioscience. EG-Y is an employee of Mount Sinai and received research funds (grants paid to her institution) from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Galderma, Glenmark/Ichnos Sciences, Innovaderm, Janssen, KAO, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals and UCB; is a consultant for AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, Leo Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB and Ventyx Biosciences. JL, APL, HP and TS are full-time employees of AbbVie and may hold AbbVie stock or stock options.

Figures

Figure 1
Figure 1
Exposure-adjusted event rates for TEAEs of special interest.* †Excluding TB, oral candidiasis and herpes zoster. ‡Defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. §Including deep vein thrombosis and pulmonary embolism. *RA: UPA 15 mg QD (n=3209), ADA 40 mg EOW (n=579), MTX (n=314); PsA: UPA 15 mg QD (n=907), ADA 40 mg EOW (n=429); AS: UPA 15 mg QD (n=182); AD: UPA 15 mg QD (n=1340), UPA 30 mg QD (n=1353). AD, atopic dermatitis; ADA, adalimumab; AS, ankylosing spondylitis; CPK, creatine phosphokinase; E, event; EOW, every other week; GI, gastrointestinal; MACE, major adverse cardiovascular event; MTX, methotrexate; NMSC, non-melanoma skin cancer; PsA, psoriatic arthritis; PY, patient years; QD, once a day; RA, rheumatoid arthritis; TB, tuberculosis; TEAE, treatment-emergent adverse event; UPA, upadacitinib; VTE, venous thromboembolic event.
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References

    1. McInnes IB, Gravallese EM. Immune-mediated inflammatory disease therapeutics: past, present and future. Nat Rev Immunol 2021;21:680–6. 10.1038/s41577-021-00603-1 - DOI - PMC - PubMed
    1. Banerjee S, Biehl A, Gadina M, et al. . JAK-stat signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs 2017;77:521–46. 10.1007/s40265-017-0701-9 - DOI - PMC - PubMed
    1. O'Shea JJ, Kontzias A, Yamaoka K, et al. . Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis 2013;72 Suppl 2:ii111–5. 10.1136/annrheumdis-2012-202576 - DOI - PMC - PubMed
    1. Fragoulis GE, McInnes IB, Siebert S. JAK-inhibitors. new players in the field of immune-mediated diseases, beyond rheumatoid arthritis. Rheumatology 2019;58:i43–54. 10.1093/rheumatology/key276 - DOI - PMC - PubMed
    1. Clarke B, Yates M, Adas M, et al. . The safety of JAK-1 inhibitors. Rheumatology 2021;60:ii24–30. 10.1093/rheumatology/keaa895 - DOI - PMC - PubMed

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