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“This analysis provides information on when clinically meaningful improvements in pain may be expected in patients with psoriatic arthritis receiving tofacitinib or adalimumab, and how baseline pain severity may impact response to tofacitinib, which is of value in clinical practice,” stated investigators.
Patients with psoriatic arthritis (PsA) receiving tofacitinib, an oral Janus kinase (JAK) inhibitor, and adalimumab experienced more pain improvements, more rapidly, than those receiving the placebo, according to a study published in BMJ Journals.1 Further, investigators discovered that patients in the tofacitinib arm with higher baseline pain had quicker pain improvements.
“This analysis provides information on when clinically meaningful improvements in pain may be expected in patients with PsA receiving tofacitinib or adalimumab, and how baseline pain severity may impact response to tofacitinib, which is of value in clinical practice,” stated investigators.
Pain, a core domain of PsA, has been historically linked to poor quality of life and a predictor of disability. In patients with PsA, pain is commonly measured on a Visual Analogue Scale (VAS), a painDETECT questionnaire for neuropathic pain, the Widespread Pain Index, and the Symptom Severity Scale, which assesses pain due to central sensitization. Investigators utilized the notion that improvements in VAS pain scores of ≥30% and ≥50% mean pain is either “much improved” or “very much improved,” respectively. It should be noted that these thresholds have not yet been validated in patients with PsA.
In this post hoc study, investigators utilized data from 2 trials: OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439), in which patients received tofacitinib 5 mg twice daily, placebo for 3 months before switching to tofacitinib 5 mg twice daily (OPAL Beyond), or adalimumab (OPAL Broaden). The patient populations from both trials were analyzed separately. Participants were excluded if they had a history of autoimmune diseases other than PsA or were diagnosed with fibromyalgia.
In addition to ≥30% and ≥50% improvement in baseline pain, median time to initial pain improvement was also estimated. Finally, a parametric model was created to understand the relationship between pain severity and time to pain response for the tofacitinib group. Any significant differences in the time to initial and continued pain improvement between the tofacitinib 5 mg twice daily versus placebo-to-tofacitinib cohorts, and the adalimumab versus placebo-to-tofacitinib cohorts were noted.
A total of 238 patients received tofacitinib 5 mb twice daily, 118 were in the placebo-to-tofacitinib group, and 106 patients received adalimumab 40 mg once every 2 weeks. Patients in OPAL Broaden (adalimumab) had generally lower pain scores, fewer swollen and tender joint counts, and shorter PsA durations when compared with the tofacitinib groups.
Results indicated that, at month 3, there were greater improvements in VAS pain scores in patients receiving either tofacitinib or adalimumab when compared with the placebo group. Additionally, the median days (95% CI) to initial/continued pain improvements were, respectively, 55/60 and 85/171 for tofacitinib, versus 106/126 and 169/NE for placebo-to-tofacitinib. Improvements in VAS pain scores were quicker in the adalimumab group versus the placebo group. In the tofacitinib cohort, pain improvement time was shorter in participants with a higher baseline pain. Data showed that 25% of patients in the tofacitinib 5 mg twice daily group could reach ≥30% pain improvements by the 2-week mark. Pain improvements of ≥30% or ≥50% were similar in both groups. In the tofacitinib 5 mg twice daily cohort, the parametric model designed to study median time to improvements from baseline showed that pain decreased more rapidly in those with higher baseline pain. Predicted median times to ≥50% improvement were 101.3 days for patients with a VAS pain score of 30 mm and only 81.1 days for patients with a VAS pain score of 80 mm.
The post hoc analysis was limited by incorporating comparisons with the placebo-only group. Further, comparisons between adalimumab and tofacitinib were not performed. Continued improvement was defined as the initial improvement over 2 visits, it was not always possible to determine when patients received clinically important and maintained pain relief. Investigators noted that, as pain is complex, the VAS may not completely capture all pain components for patients with PsA. Lastly, the inclusion/exclusion criteria from the 2 clinical trials ruled out other comorbidities that could affect the pain experienced by the patient.
“The findings from the current analysis could guide physicians in their management of patient expectations with respect to pain reduction and, in particular, when patients with PsA may expect to notice meaningful improvements with tofacitinib.”
de Vlam K, Ogdie A, Bushmakin AG, et al. Median time to pain improvement and the impact of baseline pain severity on pain response in patients with psoriatic arthritis treated with tofacitinib. RMD Open. 2021;7(2):e001609. doi:10.1136/rmdopen-2021-001609