Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Tofacitinib monotherapy has not been previously studied in PsA. This sub-study of OPAL Balance assessed tofacitinib 5 mg twice daily (BID) as monotherapy after MTX withdrawal vs with continued background MTX in patients (pts) with PsA.

Methods: OPAL Balance (NCT01976364) was an open-label (OL), long-term extension (LTE) study of tofacitinib in pts with PsA who had participated in Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]). The MTX withdrawal sub‑study was a multicenter, 12‑month, randomized, double-blind, placebo (PBO)-controlled, parallel group, estimation study of pts who had completed ≥24 months’ tofacitinib treatment in the LTE (5 mg BID; stable for ≥3 months) and were receiving oral MTX (7.5–20 mg/week; stable for ≥4 weeks) before sub-study entry. Pts remained on OL tofacitinib 5 mg BID and were randomized 1:1 to receive PBO (tofacitinib monotherapy; ie, underwent blinded MTX withdrawal) or MTX (tofacitinib + MTX; same stable doses) for 12 months. Primary endpoints were changes from sub-study baseline (BL; ∆) in Psoriatic Arthritis Disease Activity Score (PASDAS) and HAQ-Disability Index (HAQ-DI) at Month (M)6. Secondary efficacy endpoints (Table 1) were assessed at all time points. Safety (Table 2) was assessed throughout the sub-study. No specific statistical hypothesis was tested.

Results: Of 180 pts randomized, 179 were treated in the sub-study (tofacitinib monotherapy, n=90; tofacitinib + MTX, n=89). Demographics and BL characteristics were similar between tofacitinib monotherapy/tofacitinib + MTX (mean age, 53.1/51.8 yrs; female, 52.2%/55.1%; mean disease duration, 11.3/11.2 yrs; low disease activity [PASDAS ≤3.2], 70.0%/62.9%). At M6, least squares mean (LSM) (SE) ∆PASDAS was 0.229 (0.079) for tofacitinib monotherapy and 0.138 (0.081) for tofacitinib + MTX, and LSM ∆HAQ‑DI were 0.043 (0.027) and 0.017 (0.028), respectively (primary endpoints; Figure 1; Table 1); no clinically meaningful differences were observed. In general, efficacy and patient-reported outcomes were similar between treatment arms at M6 and M12 (Table 1); rates of minimal disease activity were maintained regardless of MTX withdrawal. Rates of adverse events (AEs), serious AEs, discontinuations due to AEs, and AEs of special interest were comparable between treatment arms; laboratory changes were also similar, except that elevations in liver function enzymes were more common with tofacitinib + MTX (Table 2). One (1.1%) and two (2.2%) pts receiving tofacitinib + MTX met monitoring criteria for absolute neutrophil (< 1.2 x 10³/mm³) and lymphocyte (< 0.5 x 10³/mm³) counts, respectively; no pts met discontinuation criteria (ie, values were not confirmed).

Conclusion: In general, no clinically meaningful differences in efficacy and safety were observed in pts with PsA who received OL tofacitinib 5 mg BID as monotherapy after MTX withdrawal vs with continued MTX. No new safety risks were identified. Limitations include that the sub‑study was designed as an estimation study and not powered for hypothesis testing, and only pts on long-term treatment who had responded well to, and tolerated, tofacitinib and MTX were included.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-as-monotherapy-following-methotrexate-withdrawal-in-patients-with-psoriatic-arthritis-previously-treated-with-open-label-tofacitinib-methotrexate-a-randomized-placebo-controlled-sub-st/