In a nutshell
This study examined the safety and efficacy of sirukumab in the treatment of rheumatoid arthritis.
Inflammation is a major factor in rheumatoid arthritis, leading to joint pain and swelling. Interleukin-6 is a protein involved with inflammation, and is elevated in rheumatoid arthritis patients. Therefore, new therapies are being developed to target this protein, particularly for patients who have not responded to other treatments. Sirukumab is an antibody that binds to interleukin-6, blocking it from causing inflammation. The current phase II, two-part trial examined both the safety and effectiveness of sirukumab in patients who did not respond to methotrexate (Trexall) (Part A), as well as a determination of the most effective dose of sirukumab (Part B).
Methods & findings
In Part A, 36 patients were randomly assigned to receive either 100 mg of sirukumab or placebo (a substance with no effect on the body used as a comparison) for 12 weeks, at which point patients switched groups (if they received placebo during the first 12 weeks, they then received sirukumab for 12 weeks and vice versa). Responses were measured through the American College of Rheumatology 50, criteria which indicate a 50% improvement in symptoms such as swollen, painful joints. Disease severity was also measured through the Disease Activity Score 28 – C-Reactive Protein, which measures the disease activity in 28 joints and levels of C-reactive protein in the blood (a protein that, when present, indicates inflammation in the body).
71.4% of patients receiving sirukumab had an American College of Rheumatology 20 response rate (a 20% improvement in symptoms) compared to 17.6% of the placebo group. While 28.6% of sirukumab patients achieved an American College of Rheumatology 50 response compared to 5.9% of the placebo group, this did not reach statistical significance.
A good response on the Disease Activity Score 28 was seen in 35.7% of patients receiving sirukumab, and a moderate response was seen in 57.1%. By comparison, 5.9% of placebo patients saw a good response, and 23.5% saw a moderate. The response to the drug could be measured by the second week of the study, and the response continued even when the patients were switched to the placebo.
63.2% of placebo patients and 70.6% of sirukumab patients reported at least one adverse event in the first 12 weeks, and 62.5% of placebo and 72.2% of sirukumab patients following the crossover. Infection was the most commonly reported adverse event, specifically nasopharyngitis(common cold) and upper respiratory tract infections. White blood cells, neutrophils, and platelets were all decreased following sirukumab, due to immunosuppression.
In Part B, 151 patients were randomly assigned to five groups: 30 received 100 mg of sirukumab every 2 weeks; 30 received 100 mg every 4 weeks; 30 received 50 mg every 4 weeks; 31 received 25 mg every 4 weeks; and 30 received placebo every 4 weeks. Patients were also measured through the Disease Activity Score 28 and the American College of Rheumatology 50.
In patients receiving sirukumab 100 mg every 2 weeks, 26.7% had an American College of Rheumatology 50 response rate (a more than 50% improvement in symptoms), compared to 3.3% of the placebo group. While the other sirukumab dosage groups saw symptom improvement, they did not differ significantly from the placebo group. 66.7% of the placebo patients and 67.8% of the sirukumab patients experienced an adverse event, generally infection. There were no differences in adverse events due to dosage differences.
The bottom line
This study concluded that sirukumab is a safe and effective treatment for rheumatoid arthritis patients who have not responded to other treatments.
The fine print
This trial included a relatively small number of patients. To fully measure the safety and effectiveness of sirukumab, larger trials should be done.
Published By :
Annals of the rheumatic diseases
Apr 03, 2014
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