When the investigators evaluated both the direct and indirect effects using longitudinal models adjusted for time-varying confounders, they found treatment with TNFi’s over time modified the longitudinal association between clinical ASDAS and radiographic mSASSS.The researchers documented a higher progression of ASDAS in patients never treated with TNFi’s compared with those continuously treated. In contrast, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during follow-up was not associated with a decreased progression of ASDAS. Although the study is limited by its observational nature, the investigators were able to perform robust estimates of the treatment effect, which reinforced the plausibility of the findings.
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In their discussion, the authors emphasize the potential of managing axSpA via strategies that target suppression of the clinical symptoms measured by ASDAS and other measures of inflammation, such as magnetic resonance imaging (MRI).
Need for New Treatments
Walter P. Maksymowych, MD, a rheumatologist at the University of Alberta, Canada, and senior investigator of the study says, “What we lack in treating patients with SpA is the ability to prevent the progression of their disease.”
Disease progression is slow and can take years to be reliably visualized using radiography, which makes outcomes difficult to measure in clinical trials. Untreated, the disease can lead to bone fusion in the spine. Because randomized controlled trials are difficult to justify in axSpA, the investigators turned to an observational study to address this unmet need of patients.
“We cannot allow patients to be on a placebo for two years,” says Dr. Maksymowych. The authors explain that, although patients with rheumatoid arthritis can realistically enroll in a randomized controlled trial, it’s unreasonable to expect the same of patients with SpA, especially given the fact that TNFi’s are effective in treating symptoms and may even prevent disease progression through direct biological actions on the bone, as demonstrated by the inhibition of radiographic mSASSS progression.
Thankfully, not all patients with axSpA will develop ankylosis. And TNFi’s are associated with an increased risk of infection—a risk not all patients should take on.
“We don’t have good prognostic tools, and the difference between patients is quite substantial and not easy to monitor because you have to follow people for at least two years to reliably see the change,” says Dr. Maksymowych.
Thus, he emphasizes the importance of carefully evaluating the prognostic profile of each patient. According to Dr. Maksymowych, individuals at high prognostic risk of developing ankylosis include men who have the HLA-B27 haplotype and have active inflammation, as well as patients who already have new bone formation evident on radiographs when they are first seen.5