In the phase 3 REPLENISH trial, sustained remission at 52 weeks occurred in 41% of patients receiving secukinumab compared with 20% receiving placebo.
The randomized, double-blind, placebo-controlled trial enrolled 381 patients aged 50 years or older with recently relapsed polymyalgia rheumatica at 148 sites in 28 countries. Eligible patients had experienced at least one relapse while tapering prednisone or prednisone equivalent within the previous 12 weeks and had no history or evidence of giant-cell arteritis, rheumatoid arthritis, or other inflammatory arthritis. Patients were randomly assigned in a 1:1:1 ratio to receive secukinumab 300 mg, secukinumab 150 mg, or placebo for 52 weeks. All patients received a protocol-defined 24-week prednisone taper beginning at 10 mg or 15 mg daily.
The primary endpoint was sustained remission at week 52, defined as remission achieved by week 12 and maintained through week 52 without recurrence of polymyalgia rheumatica or a new diagnosis of giant-cell arteritis that warranted treatment. Sustained remission occurred in 41% of patients receiving secukinumab 300 mg, 41% receiving secukinumab 150 mg, and 20% receiving placebo.
“Among patients with relapsed polymyalgia rheumatica, treatment with secukinumab with a 24-week glucocorticoid taper showed superior efficacy with respect to sustained remission over a 24-week glucocorticoid taper alone,” wrote lead study author John H. Stone, MD, MPH, of the Division of Rheumatology, Inflammation, and Immunology at Massachusetts General Hospital and the Division of Rheumatology, Inflammation, and Immunology at Harvard Medical School in Boston, and colleagues.
Complete sustained remission, defined as sustained remission with no elevation in inflammatory markers at 2 or more consecutive visits through week 52, occurred in 28% of patients receiving secukinumab 300 mg, 25% of patients receiving secukinumab 150 mg, and 5% of patients receiving placebo.
The adjusted mean annual cumulative glucocorticoid dose was 1,604 mg in the secukinumab 300-mg group, 1,683 mg in the secukinumab 150-mg group, and 2,093 mg in the placebo group. The researchers reported that annual cumulative glucocorticoid exposure was 20% to 23% lower among patients receiving secukinumab than among those receiving placebo.
Escape or rescue treatment was used in 51% of patients receiving secukinumab 300 mg, 52% of patients receiving secukinumab 150 mg, and 76% of patients receiving placebo. Median time to first escape or rescue treatment was 337 days, 282 days, and 157 days, respectively.
Patients receiving secukinumab also had less fatigue and better physical function scores at week 52 than patients receiving placebo. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy–Fatigue scale, and physical function was assessed with the Health Assessment Questionnaire Disability Index.
Baseline characteristics were similar across treatment groups. Mean age was 70 years, 70% of patients were women, and the median time since diagnosis was 1 year. Hypertension was present in 56% of patients, diabetes in 17%, hypercholesterolemia in 17%, and a history of fractures in 11%.
Exploratory analyses suggested less severe glucocorticoid-related toxic effects among patients receiving secukinumab. At week 52, mean Glucocorticoid Toxicity Index Aggregate Improvement Scores were 32.4 in the secukinumab 300-mg group, 54.0 in the secukinumab 150-mg group, and 84.3 in the placebo group. Mean Cumulative Worsening Scores were 69.0, 90.1, and 123.5, respectively.
Serious adverse events occurred in 14% of patients receiving secukinumab 300 mg, 16% of patients receiving secukinumab 150 mg, and 14% of patients receiving placebo.
Adverse events reported more frequently in the secukinumab groups than in the placebo group included nasopharyngitis, urinary tract infection, upper respiratory infection, back pain, fungal infection, and hypersensitivity reactions. Fungal infections occurred in 6% of patients receiving secukinumab 300 mg, 10% of patients receiving secukinumab 150 mg, and 3% of patients receiving placebo. Hypersensitivity reactions occurred in 14% of patients in each secukinumab group and 9% of patients receiving placebo. Most infections, including fungal infections, were mild to moderate and did not result in discontinuation of the trial regimen. All reported hypersensitivity reactions were nonserious and nonsevere.
Three deaths occurred during the trial. One patient in the secukinumab 150-mg group died from cryptococcal meningitis, one patient in the same group died from cardiac failure, and one patient receiving placebo died by suicide. Investigators considered the cryptococcal meningitis case potentially related to secukinumab. The other deaths were considered unrelated to the trial regimen.
The researchers noted that the trial did not provide efficacy data beyond 1 year. They also noted that higher treatment discontinuation in the placebo group than in the secukinumab groups may have resulted in underdetection of adverse events associated with conventional treatment.
“This greater efficacy was associated with a significant glucocorticoid-sparing effect,” the researchers wrote.
The trial was funded by Novartis. Full disclosures of the study authors can be found in the published study.
