Background/Purpose: Tofacitinib is a novel, oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Here we report tofacitinib safety, tolerability, and durability of response up to 60 months (mo) in long-term extension (LTE) studies.

Methods: Data were pooled from two open-label studies (A3921024 [NCT00413699], A3921041 [NCT00661661]) of patients (pts) who previously participated in randomized Phase (P)2 or P3 tofacitinib studies. Treatment was initiated with tofacitinib 5 or 10 mg BID as monotherapy or with background disease-modifying antirheumatic drugs (DMARDs); data from both doses ± background DMARDs were pooled. Baseline was that of the P2 or P3 study for pts enrolling within 7 (A3921041) or 14 (A3921024) days of participation; if enrollment was >7 or >14 days after participation, baseline was the start of the LTE study. Primary endpoints were AEs and confirmed (2 sequential) laboratory safety data. Secondary endpoints included ACR responses, DAS28‑4(ESR) (DAS28), and HAQ‑DI. Safety data were included over 72 mo of observation and efficacy data up to Mo 60 (limited pt numbers [n=39] post-Mo 60).

Results: Overall, 4827 pts were treated for a total duration of 9196 pt-years (pt‑y); mean (maximum) treatment duration was 687 (2187) days; 1246 pts (25.8%) discontinued (AEs: 616 [12.8%]; lack of efficacy: 110 [2.3%]; other: 520 [10.8%]). The most commonly reported AE classes were infections and infestations (55.8%), GI disorders (25.4%), and musculoskeletal/connective tissue disorders (27.8%). The most frequent investigator-reported AEs were nasopharyngitis (14.3%), upper respiratory tract infection (11.9%), and urinary tract infection (8.3%). Serious AEs (SAEs) were reported in 18.2% of pts with an incidence rate (IR) of 10.3 per 100 pt-y (95% CI 9.6, 11.0). Serious infection events (SIEs) were reported in 5.5% of pts with an IR of 2.9 per 100 pt‑y (95% CI 2.6, 3.3). IRs for SAEs and SIEs did not increase between 48-¹and 60-mo observations. All malignancies excluding NMSC were reported in 1.7% of pts with an IR of 0.9 per 100 pt-y (95% CI 0.7, 1.1).

Decreased hemoglobin (Hgb; ≥2 g/dL change from baseline, or Hgb <8 g/dL) was observed in 4.6% of pts. Raised aminotransferases (>3 × ULN) were observed in 2.0% (ALT) and 0.9% (AST) of pts. Moderate to severe neutropenia (absolute neutrophil count [ANC] 0.5–1.5 × 10³/mm³) was reported in 1.0% of pts; there were no cases of ANC <0.5 × 10³/mm³. Absolute lymphocyte counts <0.5 × 10³/mm³ were reported in <1.0% of pts. Increases >50% from baseline in creatinine were noted in 3.6% of pts. Mean values for laboratory safety measures were consistent with findings in P2 and P3 studies and stable over time.

Efficacy was maintained for tofacitinib ± background DMARDs between Mo 1 and Mo 60: ACR20, 60.2% and 77.9%; ACR50, 39.8% and 56.7%; ACR70, 22.7% and 40.4%, respectively. Mean DAS28 was 6.2 at baseline, 3.7 at Mo 1, and 3.6 at Mo 60. Mean HAQ-DI score was 1.4 at baseline, 0.8 at Mo 1, and 0.7 at Mo 60.

Safety and efficacy were similar for pts receiving tofacitinib as monotherapy or with background DMARDs.

Conclusion: Tofacitinib 5 or 10 mg BID in pts with RA showed a consistent safety profile and sustained efficacy over 5 years in LTE studies.

References:

1.            Wollenhaupt J et al. Arthritis Rheum 2012; 64: S548.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-an-oral-janus-kinase-inhibitor-in-the-treatment-of-rheumatoid-arthritis-open-label-long-term-extension-safety-and-efficacy-up-to-5-years/