Brief report in the journal Arthritis Care and Research shows that patients report favorable outcomes with a tofacitinib/DMARD combo therapy.
Rheumatoid arthritis patients prescribed a combination therapy of tofacitinib and a disease-modifying anti-rheumatic drug, reported significant improvements in their condition, a phase III randomized controlled trial shows. The study was published as a brief report in the Aug. 26 online issue Arthritis Care and Research.
Patient-reported outcomes can help assess the impact of disease and quality of life and are often more important to patients than what is revealed from laboratory results or joint counts.
The trial, called ORAL Sync, took place over 12 months and included 795 adult patients with rheumatoid arthritis. In the trial, patients were randomized to receive tofacitinib 5 mg or 10 mg twice daily; or a placebo of 5 mg or 10 mg twice daily in combination with a DMARD.
By month three, non-responders in the placebo group were advanced blindly to receive 5 mg or 10 mg of tofacitinib twice a day; by month six, all placebo patients were advanced blindly to receive tofacitinib. Patients in the tofacitinib groups who were nonresponders continued with the same treatment.
At month three, there were statistically significant improvements in the tofacitinib 10 mg and 5 mg groups using six assessments, with slightly better results in the tofacitinib 10 mg cohort. The improvements continued through 12 months. One key factor that improved was sleep quality, as measured by the MOS Sleep. “Sleep disturbance is associated with disease activity and pain in RA…it is encouraging, therefore, that in this trial, reported improvements in [health-related quality of life] and fatigue were accompanied by similar changes in MOS sleep,” the authors wrote.
The study results are similar to those of previous phase III randomized controlled trials of tofacitinib with rheumatoid arthritis in patients who did not adequately respond to methotrexate and biologic DMARDs, the authors reported.
Why PROs matter.
Studies that utilize patient-reported outcomes are valuable because they reflect the actual needs and desires of patients, the authors wrote.
“PROs assessing HRQoL and fatigue are considered important in RCTs of RA treatments because, in addition to being incorporated into composite disease activity measures, they reflect aspects of disease impact (such as physical function, physical and emotional wellbeing, pain, and fatigue) that are likely more important to patients than joint counts or laboratory tests,” the authors wrote.
The study limitations included a short duration of placebo exposure because advancement from placebo occurred in two stages at months three and six, the authors wrote. Another limitation was that the study did not stratify patients by background DMARD therapy, which varied among patients. Still, the results provide further evidence that tofacitinib can help improve pain, physical function, health-related quality of life, fatigue and sleep, the authors concluded.
At three months, treatment with tofacitinib 5 mg BID and 10 mg BID resulted in significantly greater improvements from baseline in PtGA, Pain, and HAQ-DI compared with placebo (P < 0.0001). The proportion of patients reporting improvements greater than the minimum clinically important differences in PtGA, Pain, and HAQ-DI at Month 3 was significantly greater with both doses of tofacitinib versus placebo (P < 0.0001).
Treatment with tofacitinib 5 mg BID and 10 mg BID resulted in significant improvements (P < 0.05) compared with placebo at Month 3 in SF-36 physical component and mental component scores, and seven of eight SF-36 domains with 5 mg BID and all eight SF-36 domains with 10 mg BID.
At three months, significantly greater mean improvements from baseline (P < 0.001) in FACIT-F and MOS Sleep were reported by patients treated with both doses of tofacitinib versus placebo.
(Source: Arthritis Care and Research)
The study was funded by Pfizer, Inc.
Vibeke Strand MD, Joel M. Kremer MD et al. "Tofacitinib in Combination with Conventional DMARDs in Patients with Active Rheumatoid Arthritis: PROs from a Phase 3 Randomized Controlled Trial," Arthritis Care and Research. Aug. 26, 2016. DOI: 10.1002/acr.23004