Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis

Gerd R Burmester; Laura C Coates; Stanley B Cohen; Yoshiya Tanaka; Ivana Vranic; Edward Nagy; Irina Lazariciu; All-Shine Chen; Kenneth Kwok; Lara Fallon; Cassandra Kinch

doi:10.1007/s40744-023-00576-8

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis

Rheumatol Ther. 2023 Oct;10(5):1255-1276. doi: 10.1007/s40744-023-00576-8. Epub 2023 Jul 17.

Authors

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
² Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Oxford, UK.
³ Metroplex Clinical Research Center and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁴ First Department of Internal Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan.
⁵ Pfizer Ltd, Tadworth, UK.
⁶ Pfizer Inc, New York, NY, USA.
⁷ Pfizer Inc, Groton, CT, USA.
⁸ Inflammation and Immunology, Pfizer Canada ULC, 17300 Trans-Canada Hwy, Kirkland, QC, H9J 2M5, Canada.
⁹ Inflammation and Immunology, Pfizer Canada ULC, 17300 Trans-Canada Hwy, Kirkland, QC, H9J 2M5, Canada. cassandra.kinch@pfizer.com.

Abstract

Introduction: The safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of ≤ 4 and 9.5 years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports have been published for RA, but not PsA. To inform the real-world safety profile of tofacitinib in PsA, we evaluated AE reports submitted to the Pfizer safety database (including RA data for context).

Methods: Endpoints included AEs, serious AEs (SAEs), AEs of special interest (AESIs; serious infections, herpes zoster, cardiovascular events, malignancies, venous thromboembolism), and fatal cases. Exposure was estimated using IQVIA global commercial sales data. Number, frequency, and reporting rates (RRs; number of events/100 patient-years' [PY] exposure) were summarized by indication and formulation (immediate release [IR] 5 or 10 mg twice daily], modified release [MR] 11 mg once daily, or all tofacitinib). The data-collection period differed by indication (PsA: 14 December 2017 [US approval, IR/MR] to 6 November 2021; RA: 6 November 2012 [US approval, IR] to 6 November 2021; MR approval, 24 February 2016).

Results: A total of 73,525 case reports were reviewed (PsA = 5394/RA = 68,131), with 20,706/439,370 PY (PsA/RA) of exposure. More AEs were reported for IR versus MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR versus IR. AE RRs (RA) in the first 4 years after IR approval were 95.9 (IR; 49,439 PY) and 147.0 (MR; 2000 PY). Frequency of SAEs, AESIs, and fatal cases was mostly similar across formulations and indications. The most frequently-reported AE Preferred Terms (PsA/RA) included drug ineffective (20.0%/17.8%), pain (9.7%/10.6%), condition aggravated (9.9%/10.5%), headache (8.8%/7.9%) and, for PsA, off-label use (10.5%/3.4%).

Conclusions: Tofacitinib PMS safety data from submitted AE reports were consistent between PsA and RA, and aligned with its known safety profile. Exposure data (lower MR versus IR; estimation from commercial sales data), reporting bias, reporter identity, and regional differences in formulation use limit interpretation.

Keywords: Post-marketing surveillance; Psoriatic arthritis; Rheumatoid arthritis; Safety; Tofacitinib.