Patients With RA With Partial Adalimumab Response May Benefit From Switch to Sarilumab

Patients with rheumatoid arthritis (RA) with a partial response to adalimumab monotherapy may have a clinically meaningful improvement or no change in disease activity after switching to sarilumab, according to study results published in The Journal of Clinical Rheumatology.

Current guidelines for the treatment of rheumatoid arthritis (RA) recommend switching therapy every 3 to 6 months, if remission or low disease activity (LDA) has not been achieved. However, patients remain on current treatment despite not achieving an adequate response.

Researchers aimed to evaluate meaningful worsening or improvement in efficacy, as well as objective outcomes, in partial responders to adalimumab monotherapy when switching to sarilumab among patients with RA. 

Data were evaluated from a multicenter phase 3 trial (MONARCH) that compared sarilumab with adalimumab monotherapy over the course of 24 weeks in patients with RA. The open-label extension (OLE) study, a subset of the MONARCH trial, included patients with RA who continued to receive adalimumab or were switched to sarilumab and were evaluated at weeks 12 and 24 of treatment.

Patients enrolled in the MONARCH trial were at least 18 years, had an RA duration of 3 or more months, C-reactive protein (CRP) levels of 8 mg/L or erythrocyte sedimentation rate (ESR) of at least 28 mm/h and with a partial response to treatment.

Partial response was defined as achieving minimal clinically important difference (MCID) in clinical disease activity (CDAI) without achieving LDA or remission. Disease activity was measured using CDAI, Health Assessment Questionnaire Disability Index (HAQ-DI), 28-joint swollen joint count (SJC28), and 28-joint tender joint count (TJC28).  Sensitivity and specificity of outcomes were also assessed.

In total, 369 patients were included in the MONARCH trial, of whom 320 (87%) entered the OLE trial (n=165 continued to receive sarilumab and 155 switched from adalimumab to sarilumab). 

In the OLE trial, at both the follow-up visits, patients in the switch group were more likely to achieve meaningful improvement (week 24 OLE: more sensitive threshold, 47%-78%; more specific threshold, 27%-66%) than worsening (week 24 OLE: more sensitive threshold, 4%-17%; more specific threshold, 2%-12%).

Partial responders were also between 4 and 24 times more likely to experience improvement rather than worsening of disease. Partial responders to sarilumab who continued to receive sarilumab also had an improvement in all measured parameters, except HAQ-DI. However, of note, improvement from baseline to OLE at week 24 was less in the continuation group compared with the switch group. 

Study limitations included expectation bias, as all patients included in the double-blinded study voluntarily switched to an open-label active treatment, and the lack of validation for meaningful worsening vs improvement thresholds.

The study authors concluded, “Taken together, our findings suggest that switching to treatment with a different mode of action at approximately 6 months is an effective approach in improving the outcomes in partial responders to biologic therapies, rather than only extending the duration of existing treatment.”

Disclosure: This research was supported by Sanofi. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.