Can Peripheral Spondyloarthritis Be Reversed?

Discussion

Dr. Carron

Dr. Carron notes, “This is the first study of the impact of first-line anti-TNF therapy in very early peripheral spondyloarthritis to achieve clinical remission after which a withdrawal was performed. This study indicates drug-free remission is an achievable target in early spondyloarthritis in at least 50% of patients.” The study extends and confirms earlier published results from the study that initiation of TNF inhibitors in very early peripheral spondyloarthritis yields remarkably high rates of remission.²

Earlier work demonstrated most patients with more long-standing forms of the disease quickly relapse after withdrawal of TNF-inhibitor therapy.³ In this study as well, patients with more established forms of disease did not respond as consistently, as indicated by the greater relapse rates in patients with oligoarthritis and patients with pre-existing psoriasis (which on average had been present for four years). Dr. Carron and colleagues speculate that in the early phase of the disease, aggressive therapy may lead to disproportionate benefits, with patients having a good chance for achieving drug-free remission. In this phase, immune dysregulation may be reversible in some patients.

“Since autoimmunity is characterized by the loss of tolerance toward self-structures, drug-free remission at the molecular level probably means not only complete suppression of disease activity, but also the reestablishment of tolerance,” Dr. Carron explains.

“Later, in the progressive phase of the disease, autoimmunity is no longer reversible,” Dr. Carron continues. “In this late phase, adequate therapy leads to moderate benefit, and patients have a low chance of remission. And it looks like there is no chance for drug-free remission. This hypothetical model suggests that, among other known and unknown factors, disease duration is a crucial risk factor for progressive disease.”

He says this hypothesis might explain the high rates of drug-free clinical remission observed in this study, in which the mean disease duration had been only five weeks.

Dr. Carron notes we don’t know the precise time frame in which the disease might become more refractory to drug withdrawal strategies. However, he believes all patients with spondyloarthritis, both axial and peripheral, might benefit from treatment during this early period when the disease appears to be more susceptible to treatment—the earlier, the better.

“Collectively, these data establish a novel therapeutic framework in defined subsets of early peripheral spondyloarthritis. This can help clinicians make the right therapeutic decisions,” says Dr. Carron.

Overall, this research can be contextualized in terms of a larger body of work studying treatment withdrawal strategies in early forms of axial spondyloarthritis. Dr. Carron notes a number of reasons may incite interest in this topic. These include introduction of the treat-to-target principle in axial spondyloarthritis, better ability to diagnose the disease in its early forms, the new use of the Ankylosing Spondylitis Disease Activity Score to evaluate scores of clinical remission and an increased interest in exploring biomarkers. Cost effectiveness also plays a role, due to the expense of TNF inhibitors.

Dr. Carron explains that such approaches, “try to reach the ultimate goal in treatment—recovery.” He also notes that in this setting TNF inhibitors are treated as class agents, because there are no head-to-head trials showing that some TNF inhibitors may be better than others.