Long-term tofacitinib efficacy and safety in psoriatic arthritis with or without prior biologic DMARD exposure: a post hoc analysis

Abstract

Objective: To assess long-term tofacitinib efficacy and safety in patients with PsA with or without prior biologic DMARD (bDMARD) exposure.

Methods: Data were pooled post hoc from three phase 3 and one long-term extension (LTE) PsA studies and stratified by TNF inhibitor-inadequate responder (TNFi-IR) or bDMARD-naïve patient status at the phase 3 study baseline. Data were reported as all tofacitinib (patients receiving one or more tofacitinib doses) or average tofacitinib 5 and 10 mg twice daily (patients receiving an average total daily dose <15 and ≥15 mg, respectively). Drug survival to month 51, efficacy to month 42 and safety were assessed descriptively.

Results: A total of 408 TNFi-IR patients (including 29 TNFi-experienced with unknown IR status) and 562 bDMARD-naïve patients were included. At baseline, TNFi-IR patients were more likely to be ≥65 years old, have cardiovascular/venous thromboembolism risk and have longer disease duration vs bDMARD-naïve patients. Drug survival was numerically shorter in TNFi-IR vs bDMARD-naïve patients. Tofacitinib efficacy was generally sustained to month 42, regardless of prior bDMARD treatment. Minimal disease activity/ PsA Disease Activity Score ≤3.2/>75% Psoriasis Area and Severity Index improvement response rates were numerically lower in TNFi-IR vs bDMARD-naïve patients to month 42, but rates of achieving an HAQ Disability Index ≤0.5 and enthesitis/dactylitis resolution were similar. In TNFi-IR vs bDMARD-naïve patients, treatment-emergent adverse event incidence rates were higher and serious adverse event, serious infection and herpes zoster incidence rates were numerically higher (CI overlapped).

Conclusion: These findings support long-term tofacitinib efficacy and safety in TNFi-IR and bDMARD-naïve patients. However, the benefit-risk profile appeared more favourable in bDMARD-naïve patients, likely due to differences in baseline characteristics and risk factors between subgroups.

Trial registration: ClinicalTrials.gov: NCT01877668, NCT01882439, NCT03486457, NCT01976364.

Keywords: JAK inhibitors; biologic therapies; interventional studies; psoriatic arthritis; tofacitinib.

Figure 1.

Time since tofacitinib initiation in the different study populations that completed the qualifying studies and the China study. Patients included in this study were randomized to receive tofacitinib 5 or 10 mg BID or placebo advancing to tofacitinib 5 or 10 mg BID at month 3 in the phase 3 index and China studies (tofacitinib 5 mg BID; placebo advancing to tofacitinib 5 mg BID only). Upon entry to OPAL Balance, all patients received open-label tofacitinib 5 mg BID. The tofacitinib dose could be increased to 10 mg BID for efficacy reasons after month 1 and reduced to 5 mg BID for safety reasons thereafter. Patients who had completed ≥24 months of the LTE study and had received stable-dose MTX for ≥4 weeks were eligible to enter a 12-month, randomized, double-blind, MTX withdrawal substudy in which patients received open-label tofacitinib plus either masked placebo or masked MTX. ^aOnly bDMARD-naïve patients from OPAL Broaden were included in this current study. ^bPatients could enter OPAL Balance ≤3 months after completing one of the qualifying index studies or discontinuing due to reasons other than a treatment-related AE. In total, 686 patients were enrolled in OPAL Balance. ^cPatients could enter the substudy if they had received tofacitinib for ≥24 months (stable at 5 mg BID for ≥3 months) and stable-dose oral MTX (7.5–20 mg/week) for ≥4 weeks. ^dAt month 3. ^ePatients were exposed to TNFi with unknown IR status and therefore were included in the TNFi-IR subgroup. P: phase

Figure 2.

Drug survival in phase 3 and LTE studies: all tofacitinib/average tofacitinib 5 mg BID. Month 0 (baseline) was the last non-missing assessment on or before day 1 of the first tofacitinib dose date for patients randomized to tofacitinib 5 or 10 mg BID or placebo to tofacitinib 5 or 10 mg BID in the phase 3 index studies. One TNFi-exposed patient with unknown IR status was included in the TNFi-IR group of the all-tofacitinib cohort. The most common reasons for discontinuation for TNFi-IR/bDMARD-naïve patients were AE(s) (all tofacitinib: 12.6%/12.6%; average tofacitinib 5 mg BID: 10.9%/13.7%), no longer willing to participate in the study (all tofacitinib: 10.5%/11.3%; average tofacitinib 5 mg BID: 8.9%/10.3%) and insufficient clinical response (all tofacitinib: 8.9%/2.6%; average tofacitinib 5 mg BID: 6.3%/1.5%). Tofa: tofacitinib

Figure 3.

Clinical efficacy in phase 3 and LTE studies: all tofacitinib/average tofacitinib 5 mg BID (NRI). Month 0 (baseline) was the last non-missing assessment on or before day 1 of the first tofacitinib dose date for patients randomized to tofacitinib 5 or 10 mg BID or placebo to tofacitinib 5 or 10 mg BID in the phase 3 index studies. One TNFi-exposed patient with unknown IR status was included in the TNFi-IR group of the all-tofacitinib cohort. ^aAssessed every 6 months in the LTE study. ^bAssessed in patients with baseline HAQ-DI >0.5. N: number of patients at baseline; n: number of patients who achieved the corresponding state; Tofa: tofacitinib

Figure 4.

PsA manifestations in phase 3 and LTE studies: all tofacitinib/average tofacitinib 5 mg BID (NRI). Month 0 (baseline) was the last non-missing assessment on or before day 1 of the first tofacitinib dose date for patients randomized to tofacitinib 5 or 10 mg BID or placebo to tofacitinib 5 or 10 mg BID in the phase 3 index studies. One TNFi-exposed patient with unknown IR status was included in the TNFi-IR group of the all-tofacitinib cohort. N: number of patients at baseline; n: number of patients with response; Tofa: tofacitinib