Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we report tofacitinib safety, tolerability, and durability of response through 72 months (mo) in long-term extension (LTE) studies.

Methods: Data were pooled from two open-label studies (NCT00413699 [ongoing; database unlocked as of April 2014 data cut-off] and NCT00661661) of patients (pts) with RA who participated in randomized Phase (P)1, P2, or P3 tofacitinib studies. Treatment was initiated with tofacitinib 5 or 10 mg BID as monotherapy or with background DMARDs; data from both doses ± background DMARDs were pooled. Baseline (BL) was that of P1, P2, or P3 studies for pts enrolling within 14 days of participation; for all other pts, BL was the start of the LTE study. Primary endpoints were adverse events (AEs) and laboratory safety data. Confirmed (2 sequential abnormalities) data are reported for decreased hemoglobin (HgB), absolute neutrophil counts, absolute lymphocyte counts, and increases >50% from BL in creatinine. Secondary endpoints included ACR responses, DAS28-4(ESR), and HAQ-DI. Safety data were included over 84 mo and efficacy data up to Mo 72 (limited pt numbers [n≤29] post-Mo 72 for efficacy).

Results: Overall, 4,858 pts were treated for a mean (maximum) duration of 918 (2,535) days. Total tofacitinib exposure was 12,359 pt-years (pt-y). In total, 1747 pts (36.0%) discontinued (AEs: 866 [17.8%]; insufficient clinical response: 133 [2.7%]). The most commonly reported classes of AEs were infections and infestations (63.4%), musculoskeletal/connective tissue disorders (33.9%), and GI disorders (29.9%). The most frequently reported individual AEs were nasopharyngitis (16.3%), upper respiratory tract infection (14.5%), and urinary tract infection (10.3%). Serious AEs (SAEs) were reported in 19.0% of pts with an incidence rate (IR) of 8.1 per 100 pt-y (95% CI 7.6, 8.7). Serious infection events (SIEs) were reported in 7.2% of pts with an IR of 2.9 per 100 pt-y (95% CI 2.6, 3.2). All malignancies excluding NMSC were reported in 2.4% of pts with an IR 1.0 per 100 pt-y (95% CI 0.8, 1.2). IRs for SAEs, SIEs and malignancies through Mo 84 did not increase compared with previously reported data through Mo 72.¹ Decreased Hgb (>2 g/dL change from BL, or Hgb <8 g/dL) was observed in 5.7% of pts. Increased aminotransferases (>3 × ULN) were observed in 4.7% (ALT) and 2.6% (AST) of pts. Moderate to severe neutropenia (absolute neutrophil count [ANC] 0.5–1.5 × 10³/mm³) was reported in 1.2% of pts; there were no cases of ANC <0.5 × 10³/mm³. Absolute lymphocyte counts <0.5 × 10³/mm³were reported in 1.1% of pts. Increases >50% from BL in creatinine were noted in 3.4% of pts. ACR20, ACR50, and ACR70 response rates for tofacitinib were sustained between Mo 1 (72.7%, 48.7%, and 29.0%, respectively) and Mo 72 (80.8%, 62.8%, and 37.2%, respectively). Mean DAS28‑4(ESR) was 6.29 at BL, 3.74 at Mo 1, and 3.32 at Mo 72. Mean HAQ-DI score was 1.42 at BL, 0.81 at Mo 1, and 0.77 at Mo 72.

Conclusion: A consistent safety profile and sustained efficacy through 72 mo was observed in patients with RA receiving tofacitinib at either 5 or 10 mg BID in LTE studies.

References:
   1.         Wollenhaupt J et al. Arthritis Rheum 2013; 65: S2328.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-an-oral-janus-kinase-inhibitor-in-the-treatment-of-rheumatoid-arthritis-safety-and-efficacy-in-open-label-long-term-extension-up-to-6-years/