Tofacitinib With Methotrexate in Third‐Line Treatment of Patients With Active Rheumatoid Arthritis: Patient‐Reported Outcomes From a Phase III Trial

Abstract

Objective. To assess patient-reported outcomes (PROs) for tofacitinib, an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA), in a 6-month, phase III, randomized controlled trial. Methods. Patients ages >18 years with active RA with an inadequate response to >1 tumor necrosis factor inhibitor (TNFi) and receiving stable background methotrexate were randomized 2:2:1:1 to tofacitinib 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib 5 mg or 10 mg twice daily at month 3. PROs measured at month 3 included patient global assessment of disease activity ( Results. Patients received tofacitinib 5 mg (n ‫؍‬ 133) or 10 mg (n ‫؍‬ 134) or placebo advanced to tofacitinib 5 mg (n ‫؍‬ 66) or 10 mg (n ‫؍‬ 66). HAQ DI (reported previously), PtGA (P < 0.0001), and SF-36v2 physical and mental component summary (P < 0.05) scores were improved for both tofacitinib doses versus placebo. Furthermore, improvements greater than or equal to the minimum clinically important difference were more frequently reported by tofacitinib-treated patients versus placebo for PtGA (P < 0.05), pain (P < 0.0001), HAQ DI (P < 0.05), SF-36v2 physical and mental component summary scores (P < 0.05), and FACIT-F (P < 0.001 for 5 mg twice daily). No statistical differences were observed in the MOS Sleep Scale. Conclusion. Tofacitinib treatment resulted in significant, clinically meaningful improvements in multiple PROs versus placebo over 3 months of treatment in patients with active RA and a previous inadequate response to TNFi.

Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON)

“…Patients receiving baricitinib also reported a significant improvement in EQ-5D scores, pain, MJS duration and fatigue as well as in regular activity (WPAI-RA) compared with the placebo group. By contrast, for the SF-36 MCS measure, no significant differences were observed between patients treated with baricitinib compared with placebo, consistent with previous observations from other clinical trials 26 27 34 35. The baseline value of the MCS was approximately 46 across the treatment groups, demonstrating only a modest impairment, in contrast to the significant physical impairment seen with the PCS (approximately 29 at baseline).…”

“…In a randomised controlled trial of tofacitinib in patients with inadequate response to TNFis (but overall much lower proportions of patients with multiple bDMARD failure), the PROs reported included pain, PtGA, HAQ-DI, FACIT-F, SF-36 and MOS Sleep Scale 26 39. Treatment effects from that study26 39 are consistent with our data showing meaningful outcomes for patients treated with JAK inhibitors.…”

“…Improvements in PROs associated with baricitinib in the present analysis were in the range of those reported with bDMARDs in patients with just an inadequate response to csDMARDs or to TNFis 26 27 34 35–37. Over 6 months, the difference in the rates of patients showing improvement that was ≥MCID in the HAQ-DI and the SF-36 PCS, amounted to 23% between baricitinib 4 mg and placebo.…”

“…For the FACIT-F, a three to four-point change has been considered an MCID,25 26 and in this study a value of 3.5627 was used to assess the clinical relevance of changes in FACIT-F scores. Duration of morning joint stiffness (MJS) was reported by the patient as the length of time (minutes) that MJS lasted on the day prior to the study visit.…”

Examination of Patient-Reported Outcomes in Association with TNF-Inhibitor Treatment Response: Results from a US Observational Cohort Study

“…Of note, in this cohort of patients, patients at the lower end of the spectrum of M/HDA at TNFi initiation experienced a greater magnitude of change in PROs at 12 months, compared with patients who had higher baseline levels of disease activity. These findings from the Corrona registry, a real-world cohort of patients with RA, are similar to those reported in several recent phase III randomized clinical trials (RCTs), including RA- Table 4 Time to switch by reasons for switching [18][19][20][21].…”