Frequency and Duration of Early Non-serious Adverse Events in Patients with Rheumatoid Arthritis and Psoriatic Arthritis Treated with Tofacitinib

Ara Dikranian, David Gold, Louis Bessette, Peter Nash, Valderilio F Azevedo, Lisy Wang, John Woolcott, Andrea B Shapiro, Annette Szumski, Dona Fleishaker, Jürgen Wollenhaupt, Ara Dikranian, David Gold, Louis Bessette, Peter Nash, Valderilio F Azevedo, Lisy Wang, John Woolcott, Andrea B Shapiro, Annette Szumski, Dona Fleishaker, Jürgen Wollenhaupt

Abstract

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This post hoc analysis assessed frequency or duration of early select non-serious adverse events (AEs; excluding infections), and their impact on treatment discontinuation, in patients with RA or PsA treated with tofacitinib 5 or 10 mg twice daily, or placebo.

Methods: Data were pooled from five phase 3 and one phase 3b/4 studies in patients with moderate-to-severe RA, and two phase 3 studies in patients with active PsA. Select all-causality, non-serious AEs, reported to month 3 (placebo-controlled period), were headache, diarrhea, nausea, vomiting, and gastric discomfort (including dyspepsia, gastritis, epigastric discomfort, and abdominal discomfort or pain); incidence rates (unique patients with events per 100 patient-years of follow-up), duration of, and discontinuations due to these non-serious AEs were reported.

Results: We analyzed 3871 and 710 patients with RA and PsA, respectively. Incidence of non-serious AEs to month 3 was generally similar with tofacitinib and placebo. The most frequent non-serious AEs were headache and diarrhea with tofacitinib, and dyspepsia, nausea, and headache with placebo. Most events were mild or moderate in severity, lasting ≤ 4 weeks. Permanent discontinuations due to non-serious AEs were not observed in patients with PsA, and were < 1.0% in patients with RA across treatment groups. The most frequent cause of temporary discontinuation across all groups was gastric discomfort (0.3-0.8%).

Conclusions: Non-serious AE incidence was generally similar in patients with RA or PsA receiving tofacitinib or placebo. Most events were mild or moderate and generally resolved within 4 weeks.

Trial registration: ClinicalTrials.gov identifiers: NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01877668; NCT01882439; NCT02187055.

Keywords: Adverse event; Antirheumatic agents; Autoimmune diseases; Psoriatic arthritis; Rheumatoid arthritis; Tofacitinib; Tolerability.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Duration of non-serious AEs up to month 3 in patients with RA: HLGT headachea (a), diarrheab (b), nauseab (c), vomitingb (d), and gastric discomfort (composite term)c (e). AEs are shown as percentages of the total number of patients experiencing the specified AE in each treatment group. Data are shown for patients receiving tofacitinib 5 or 10 mg BID, or placebo, as monotherapy or in combination with csDMARDs in phase 3 and phase 3b/4 studies. aMedDRA HLGT, including all types of headache (see the Supplementary Methods in the electronic supplementary material for a full list of preferred terms included). bPreferred term. cA composite term comprised of selected preferred terms, including dyspepsia, gastritis, epigastric discomfort, and abdominal discomfort or pain (see the Supplementary Methods in the electronic supplementary material for a full list of preferred terms included). AE adverse event, BID twice daily, csDMARD conventional synthetic disease-modifying antirheumatic drug, HLGT higher-level group term, MedDRA Medical Dictionary for Regulatory Activities, n total number of patients experiencing the specified AE in each treatment group, RA rheumatoid arthritis
Fig. 2
Fig. 2
Duration of non-serious AEs up to month 3 in patients with PsA: HLGT headachea (a), diarrheab (b), nauseab (c), vomitingb (d), and gastric discomfort (composite term)c (e). AEs are shown as percentages of the total number of patients experiencing each AE in each treatment group. Data are shown for patients receiving tofacitinib 5 or 10 mg BID, or placebo, in combination with csDMARDs in phase 3 studies. aMedDRA HLGT, including all types of headache (see the Supplementary Methods in the electronic supplementary material for a full list of preferred terms included). bPreferred term. cA composite term comprised of selected preferred terms, including dyspepsia, gastritis, epigastric discomfort, and abdominal discomfort or pain (see the Supplementary Methods in the electronic supplementary material for a full list of preferred terms included). AE adverse event, BID twice daily, csDMARD conventional synthetic disease-modifying antirheumatic drug, HLGT higher-level group term, MedDRA Medical Dictionary for Regulatory Activities, n total number of patients experiencing the specified AE in each treatment group, PsA psoriatic arthritis

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