New biologic drug shows promising results in treating osteoarthritis.
For a number of years, biologic drugs, in particular monoclonal antibodies, have routinely been used to treat rheumatoid arthritis. However, osteoarthritis has largely been managed with pain relief, oral anti-inflammatory drugs, and occasionally localised injections of drugs to reduce inflammation at the joint site. The difference in approaches came down to the understanding of the disease mechanisms. Rheumatoid arthritis is known to be an autoimmune disease whereas osteoarthritis was generally considered the result of wear and tear. However, improved understanding of the disease process in osteoarthritis has uncovered a significant inflammatory component mediated by many of the same signalling proteins as seen in rheumatoid arthritis.
As a result, the development of new treatments for osteoarthritis has included a new focus on biologic drugs. A study recently published in the Annals of Internal Medicine, reports on a clinical trial of one such biological drug, canakinumab (1). The primary goal of this large clinical trial was to determine whether canakinumab had a beneficial cardiovascular effect. However, this study is an exploratory analysis using the trial data to also explore the effectiveness of canakinumab for osteoarthritis.
Canakinumab for osteoarthritis
Canakinumab is a biological drug which has been used for a number of years to treat auto-inflammatory diseases. It works by targeting a particular signalling molecule called interleukin-1 beta or IL-1B. This molecule is produced in increased quantities in a variety of auto-inflammatory conditions, but evidence in recent years has suggested it may also play a role in osteoarthritis.
As osteoarthritis is a progressive disorder, patients who initially develop a problem in their knees or hips frequently end up requiring a total knee replacement (TKR) or total hip replacement (THR). The rate of replacement among the study population was used as the marker of disease progression in this study.
The trial involved over 10,000 patients spread across 1,091 sites in 39 countries. Participants were randomly assigned to receive either placebo or one of three doses of canakinumab by subcutaneous injection every three months. As disease progression in osteoarthritis is often relatively slow, the follow-up time in this study needed to be significant. The median follow-up time was 3.7 years. All three doses of canakinumab demonstrated a reduction in the risk of total knee or total hip replacement compared to placebo. In the pooled canakinumab group, the hazard ratio for THR/TKR was 0.58, with 0.31 events per 100 person-years compared to 0.54 in the placebo group. There was also a slightly smaller reduction in the likelihood of osteoarthritis related adverse events in the treatment group.
One of the major limitations of this report is the choice of outcome measure. Total knee or hip replacement is one marker of disease progression in osteoarthritis. However, it is not a marker of day-to-day disease experience. The decision to proceed with THR/TKR can also be influenced by a number of other non-disease related factors such as healthcare system in the country, a patient’s insurance coverage, and the age and comorbidities of patients. The absence of any information on structural joint outcomes, a more appropriate marker of progression, is a weakness of the study acknowledged by the authors.
However, these results are significant because there is currently no known drug treatment that effectively prevents disease progression in osteoarthritis. Further research is needed to demonstrate if canakinumab for osteoarthritis is indeed an effective treatment but the results of this exploratory analysis are extremely promising.
Written by Michael McCarthy
1. Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement. Ann Intern Med. https://doi.org/10.7326/M20-0527
