Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial

Abstract

Objective: To provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR).

Methods: ORAL Strategy (NCT02187055), a phase IIIB/IV, head-to-head, randomised controlled trial, assessed non-inferiority between tofacitinib 5 mg two times per day monotherapy, tofacitinib 5 mg two times per day+MTX and ADA 40 mg every other week+MTX. PROs assessed included the following: Patient Global Assessment of disease activity (PtGA), Pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and 36-Item Short-Form Health Survey (SF-36) summary and domain scores.

Results: Substantial improvements from baseline were reported across all PROs in all treatment arms, which, in the majority, met or exceeded minimum clinically important differences. Compared with tofacitinib monotherapy, tofacitinib+MTX combination treatment conferred significantly greater improvements in PtGA, Pain and SF-36 physical component summary scores at month 6. Statistically or numerically greater improvements were often, but not uniformly, reported for combination treatments compared with tofacitinib monotherapy at other time points.

Conclusion: Treatment with tofacitinib+MTX, ADA+MTX and tofacitinib monotherapy resulted in clinically meaningful improvements in PROs in MTX-IR patients with RA. These were comparatively greater with combination treatments versus tofacitinib monotherapy, although differences between treatment arms were small, limiting our ability to confer clinical meaning.

Trial registration number: NCT02187055.

Keywords: DMARDs (biologic); DMARDs (synthetic); outcomes research; rheumatoid arthritis.

Figure 1

PRO scores over time for (A) PtGA, (B) Pain, (C) HAQ-DI, (D) FACIT-F, (E) SF-36 PCS and (F) SF-36 MCS (FAS). PtGA and Pain were assessed using 0–100 mm VAS. N numbers evaluable for each outcome may be ≤ those reported for the FAS. *p<0.05 tofacitinib+MTX versus tofacitinib monotherapy; **p<0.01 tofacitinib+MTX versus tofacitinib monotherapy; ^†p<0.05 ADA+MTX versus tofacitinib monotherapy; ^††p<0.01 ADA+MTX versus tofacitinib monotherapy; ^‡p<0.05 tofacitinib+MTX versus ADA+MTX. ADA, adalimumab; BID, two times per day; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FAS, full analysis set; HAQ-DI, Health Assessment Questionnaire-Disability Index; LSM, least squares mean; MCID, minimum clinically important difference; MCS, mental component summary; MTX, methotrexate; Pain, arthritis pain; PCS, physical component summary; PtGA, Patient Global Assessment of Disease Activity; PRO, patient-reported outcome; SE, standard error; SF-36, 36-Item Short-Form Health Survey; VAS, visual analogue scale.

Figure 2

Proportion of patients reporting improvements ≥MCID in (A) PtGA, (B) Pain, (C) HAQ-DI, (D) FACIT-F, (E) SF-36 PCS and (F) SF-36 MCS (FAS). MCID: ≥10 mm decrease from baseline in PtGA and Pain; ≥0.22-point decrease from baseline in HAQ-DI score; ≥2.5-point increase from baseline in SF-36 PCS and MCS scores; ≥4-point increase from baseline in FACIT-F score. *p<0.05 tofacitinib+MTX versus tofacitinib monotherapy; **p<0.01 tofacitinib+MTX versus tofacitinib monotherapy; ^†p<0.05 ADA+MTX versus tofacitinib monotherapy; ^‡p<0.05 tofacitinib+MTX versus ADA+MTX; ^‡‡p<0.01 tofacitinib+MTX versus ADA+MTX. ADA, adalimumab; BID, two times per day; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FAS full analysis set; HAQ-DI, Health Assessment Questionnaire-Disability Index; MCID, minimum clinically important difference; MCS, mental component summary; MTX, methotrexate; Pain, arthritis pain; PCS, physical component summary; PtGA, Patient Global Assessment of Disease Activity; SF-36, 36-Item Short-Form Health Survey.

Figure 3

The proportion of patients reporting (A) Pain scores <20 mm over time, and (B) ≥20%, 30%, 50% or 70% improvements in Pain at month 6 (FAS). *p<0.05 tofacitinib+MTX versus tofacitinib monotherapy; **p<0.01 tofacitinib+MTX versus tofacitinib monotherapy; ^†p<0.05 ADA+MTX versus tofacitinib monotherapy; ^††p<0.01 ADA+MTX versus tofacitinib monotherapy. ADA, adalimumab; BID, two times per day; FAS, full analysis set; MTX, methotrexate; Pain, arthritis pain.

Figure 4

Spydergrams representing mean SF-36 domain scores over time for (A) tofacitinib 5 mg two times per day, (B) tofacitinib 5 mg two times per day+MTX and (C) ADA+MTX. The sample sizes indicated represent the number of patients who took the SF-36 at that visit. Some domains may have had one to two patients fail to respond. ADA, adalimumab; AG norms, age-matched and gender-matched norms; BID, two times per day; BP, Bodily Pain; GH, General Health; MH, Mental Health; MTX, methotrexate; PF, Physical Functioning; RE, Role Emotional; RP, Role Physical; SF, Social Functioning; SF-36, 36-Item Short-Form Health Survey; VT, Vitality.