The primary end point was the proportion of patients at 52 weeks who achieved sustained remission, defined as being in disease remission by week 12, along with the absence of disease flare, sustained C-reactive protein (CRP) normalization and adherence to the glucocorticoid taper, all from weeks 12 to 52. Key secondary end points included each component of the sustained remission outcome, the time until the first disease flare after remission, the cumulative glucocorticoid dose over 52 weeks and safety.
Results
“Patients treated with sarilumab were three times more likely to achieve the primary outcome at 52 weeks, despite being treated with a very rapid corticosteroid taper,” says Dr. Spiera.
At 52 weeks, 28% of patients who received sarilumab and 10% of patients who received placebo achieved the primary end point (P=0.02). Patients who received sarilumab (47%) were more likely than those on placebo (38%) to achieve clinical remission at 12 weeks and avoid disease flare after this (55% vs. 33%). The remaining components of the sustained remission outcome also favored sarilumab over placebo. The respective rates for sustained CRP normalization were 67% and 45%, and for glucocorticoid taper adherence were 50% and 24%.
At all follow-up visits, the proportion of patients without signs and symptoms of PMR was higher with sarilumab than with placebo. The respective rates were 57% and 49% at 16 weeks and 81% and 57% at 52 weeks. Despite a faster glucocorticoid taper, a lower proportion of patients who received sarilumab (32%) required additional rescue therapy with glucocorticoids during the study than those who received placebo (59%). At week 52, the median cumulative glucocorticoid dose was lower in the sarilumab group, at 777 mg, vs. 2,044 mg in the placebo group (P<0.001).
Despite a rapid corticosteroid taper, “we found that sarilumab patients were much more likely to remain in remission. There was also a significantly smaller amount of steroid exposure in the sarilumab-treated patients. And importantly, patient-reported outcomes assessing quality of life and function all favored treatment with sarilumab,” says Dr. Spiera.
The results suggested that patients who received sarilumab fared better than those who received placebo in patient-reported quality of life and function measures, including the Short Form-36 Mental Component and Physical Component Scores, the EuroQol-5 Dimension (EQ-5D) scale, the Functional Assessment of Chronic Illness Therapy (FACITfatigue) score and the Health Assessment Questionnaire-Disability Index (HAQ-DI).
No new safety signals were found during the study. The most common adverse events with sarilumab were neutropenia (15%), arthralgia (15%), diarrhea (12%) and hypertension (10%). More treatment-related discontinuations were reported in the patients on sarilumab (12%) than those on placebo (7%), driven primarily by a higher incidence of neutropenia with sarilumab use.
