Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis

Abstract

Objective: To evaluate effects of tofacitinib or adalimumab on patient-reported outcomes (PROs) in patients with moderate to severe RA and inadequate responses to MTX.

Methods: In this 12-month, phase 3, randomized controlled trial (ORAL Standard), patients (n = 717) receiving background MTX were randomized to tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks or placebo. PROs included HAQ-Disability Index, Patient Global Assessment of Arthritis, Patient Assessment of Arthritis Pain, health-related quality of life (Short Form-36 [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) and sleep (Medical Outcomes Study-Sleep).

Results: At month 3, tofacitinib 10 mg BID treatment resulted in significant changes from baseline vs placebo across all PROs, sustained to month 12, with the highest number of patients reporting improvements ⩾minimum clinically important differences vs placebo (P < 0.05). Changes from baseline at month 3 with tofacitinib 5 mg BID and adalimumab were similar and statistically significant vs placebo across most PROs, excluding SF-36 Mental Component Score and Social Functioning, Role Emotional, and Mental Health domains, with significantly more patients reporting improvements ⩾minimum clinically important differences. Numbers Needed to Treat were lowest for tofacitinib 10 mg BID and similar between tofacitinib 5 mg BID and adalimumab.

Conclusion: Patients with moderate to severe RA and inadequate responses to MTX reported improvements across a broad range of PROs with tofacitinib 5 and 10 mg BID and adalimumab that were significantly superior to placebo.

Keywords: Janus kinase; patient-reported outcomes; phase 3; rheumatoid arthritis; tofacitinib.

Fig. 1

Spydergram^©a representing mean overall SF-36 domain scores at month 3 (full analysis set, no imputation) All patients received background MTX. ^aStudy values were normed using population mean and standard deviations, see [24]. ^b(A–E) report treatment group baselines (A using separate colours); (F) reports weighted combined baseline across all treatment groups. Placebo, n = 106 at baseline and n = 99 at month 3; tofacitinib 5 mg BID, n = 201 at baseline and n = 188 at month 3; tofacitinib 10 mg BID, n = 199 at baseline and n = 185 at month 3; adalimumab, n = 201 at baseline and n = 190 at month 3. BID: twice daily; BP: Bodily Pain; GH: General Health; MH: Mental Health; MTX: methotrexate; PF: Physical Functioning; Q2W: once every 2 weeks; RE: Role Emotional; RP: Role Physical; SC: subcutaneous; SF: Social Functioning; SF-36: Short Form-36; VT: Vitality.

Fig. 2

LSM (SE) change from baseline (full analysis set, longitudinal model) *P ≤ 0.05, **P < 0.001 and ***P < 0.0001 vs placebo + MTX. (A) Physical Functioning (HAQ-DI); (B) Patient Global Assessment of Arthritis; and (C) Patient Assessment of Arthritis Pain. Each individual graph has two separate analyses plotted. For baseline to month 6, patients who advanced at month 3 had their month 6 value set to missing for the purpose of statistically testing vs placebo. For post-month 6, all available patient data are included. BID: twice daily; HAQ-DI: Health Assessment Questionnaire-Disability Index; LSM: least squares mean; MTX: methotrexate; Pain: Patient Assessment of Arthritis Pain; PtGA: Patient Global Assessment of Arthritis; Q2W: once every 2 weeks; SC: subcutaneous; SE: standard error.

Fig. 3

LSM (SE) change from baseline in HRQoL (SF-36) (full analysis set, longitudinal model) *P ≤ 0.05, **P < 0.001 and ***P < 0.0001 vs placebo + MTX. (A) Physical Component Summary score; (B) Mental Component Summary score. Each individual graph has two separate analyses plotted. For baseline to month 6, patients who advanced at month 3 had their month 6 value set to missing for the purpose of statistically testing vs placebo. For post-month 6, all available patient data are included. BID: twice daily; HRQoL: health-related quality of life; LSM: least squares mean; MCS: Mental Component Summary; MTX: methotrexate; PCS: Physical Component Summary; Q2W: once every 2 weeks; SC: subcutaneous; SE: standard error; SF-36: Short Form-36.

Fig. 4

LSM (SE) change from baseline (full analysis set, longitudinal model) *P ≤ 0.05, **P < 0.001 and ***P < 0.0001 vs placebo + MTX. (A) Fatigue (FACIT-F); (B) sleep (MOS-Sleep). Each individual graph has two separate analyses plotted. For baseline to month 6, patients who advanced at month 3 had their month 6 value set to missing for the purpose of statistically testing vs placebo. For post-month 6, all available patient data are included. BID: twice daily; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; LSM: least squares mean; MOS: Medical Outcomes Study; MTX: methotrexate; Q2W: once every 2 weeks; SC: subcutaneous; SE: standard error.