Disease-modifying antirheumatic drugs (DMARDs) do not offer patients with osteoarthritis (OA) clinically significant pain relief relative to placebo, according to a meta-analysis

Monica S.M. Persson, a graduate student at the University of Nottingham, United Kingdom, and colleagues published results from the first meta-analysis of conventional and biologic DMARDs for OA June 16 in Rheumatology.

The researchers analyzed results from 11 randomized controlled trials (RCTs) that were published as conference abstracts and scientific papers. The RCTs included 1205 participants; half of the trials (757 participants) evaluated conventional DMARDs and half (448 participants) evaluated biologics.

Although DMARDs were statistically superior to placebo [effect size (ES), 0.18; 95% confidence interval [CI], 0.03 – 034], the difference was not clinically significant (0.5 ES threshold).

DMARDs and Arthritis

In general, DMARDs target the innate immune response via interleukin (IL)-1, the adaptive immune response via tumor necrosis factor (TNF), or overall inflammation (e.g., methotrexate). Whereas results from in vitro studies and animal models have suggested that biologic DMARDs could be useful in the treatment of OA, RCTs indicate that they do not provide a clear benefit over placebo.

"We have followed the literature on this and realized that trials were largely negative," Persson told Medscape Medical News. "However, our study has, for the first time, fully examined and quantified the efficacy of the drugs in OA using meta-analysis."

Not only did the investigators find that DMARDs were ineffective for OA, but they also found no difference in efficacy between anti–IL-1 and anti-TNF biologics. The same held true for different joint sites and OA subtypes, with no statistically significant differences in any of the subanalyses.

Causes of Osteoarthritis

OA tends to result from wear and tear. That said, "Over the past few years, people have gotten interested in the role of inflammation in osteoarthritis," explained MacFarlane.

The authors have interpreted their findings, however, to mean that inflammation may not be a prime driver for OA pain.

"There is much debate about the role of inflammation in OA — some believe that inflammation is a primary driver of structural change and pain in OA, whilst others believe that any inflammation that is present is part of the repair process of the joint that is triggered largely by mechanical or metabolic drivers," explained Persson.

"DMARDs can effectively manage arthritis that is driven by primary injurious inflammation that both damage joints and cause pain. Our findings would suggest that such primary inflammation is not a key driver of OA pain."

Inflammation and Osteoarthritis

MacFarlane explained her interest in the intersection of obesity, inflammation, and osteoarthritis, noting that studies of hand OA have revealed an increased incidence in individuals who are obese.

The location of OA in the hand of individuals who are obese suggests that the OA results not from increased mechanical load associated with obesity, such as would be seen in the knee. Instead, the increased incidence of hand OA may be associated with obesity in another way, perhaps through inflammation.

Moreover, "there is a lot of literature to suggest that inflammation matters in OA," emphasized MacFarlane. However, she acknowledged that pain is multifactorial and that although individuals with inflammation tend to have more pain, the relationship is not absolute.

In some patients, inflammation may drive pain. Other patients appear to have additional factors that are major contributors to the sensation of pain. All patients with OA, however, represent an unmet medical need.

"The field is begging for treatments that will halt the progression of the disease," emphasized MacFarlane. Patients with OA do not yet have such options.