A post-hoc analysis of 3 randomized controlled trials reports on the associations between the IL-6 inhibitor and unacceptable or refractory pain.
Treatment with sarilumab in rheumatoid arthritis patients was associated with lower odds of unacceptable or refractory pain compared with placebo or adalimumab.
These findings were presented at the Clinical Congress of Rheumatology (CCR) East 2020.
Unacceptable pain levels may persist in patients as a result of ongoing joint inflammation. Furthermore, this type of pain may continue despite attempts to quell the inflammation., which suggests the pain to be a result of other mechanisms.
Current evidence points to the possibility of the IL-6 receptor’s contribution to pathological pain due to its unique downstream molecular and cellular mechanisms.
Vivian Bykerk, MD, rheumatologist at the Hospital for Special Surgery, New York, and colleagues conducted a post-hoc analysis of the TARGET, MOBILITY, and MONARCH studies to assess the association between the IL-6 inhibitor sarilumab and persistent unacceptable pain despite inflammation control.
In all 3 Phase 3 randomized controlled trials, subcutaneous administration of sarilumab 150 mg or 200 mg every 2 weeks led to meaningful improvements in pain—versus placebo or other therapies—and demonstrated an acceptable safety profile.
In Bykerk and team’s post-hoc analysis, they determined the odds ratios of unacceptable pain and refractory pain despite inflammation control. They were also interested in the associations between pain and fatigue, disease activity, swollen joint count, and tender joint count.
And finally, using the Kappa coefficient test on interrator reliability, they looked at the agreements among the studies on the likelihood of achieving minimal clinically importance differences (MCID) on all outcomes.
They noted that among the study arms in each trial, baseline characteristics were similar.
By the end of the trials, patients receiving either doses of sarilumab generally experienced better inflammation control and lower of rates of unacceptable pain—versus comparators.
Furthermore, the trials showed that both doses of the drug had lowers odds of unacceptable pain compared with placebo or adalimumab.
Although the odds of refractory pain despite inflammation control was lower for sarilumab in the MOBILITY trial, the TARGET and MONARCH trials showed no differences between the comparators.
Higher pain level was associated with worse levels of fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue), disease activity (Health Assessment Questionnaire Disbaility Index [HAQ-DI]), swollen joint count, and tender joint count.
The investigators reported that unacceptable pain had mostly moderate agreements with the likelihood of achieving response (MCID) on the previous outcomes.
When adjusting for complete control of inflammation, they found that persisting pain was more common in patients who had a longer duration of the disease at baseline and/or had consistently failed other treatments, such as conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or tumor necrosis factor inhibitors (TNFi).
“Further research is needed regarding the sources of persistent pain and the potential role of inflammation control in patients with [rheumatoid arthritis] given that no significant differences were noted in two out of three studies when evaluating pain despite inflammation control,” they concluded.
The study, “Impact of Sarilumab on Unacceptable Pain and Inflammation Control in Moderately to Severely Active Rheumatoid Arthritis Patients in Three Phase 3 Studies,” was presented at CCR East 2020.