Optimized Treatment Strategies in Axial Spondyloarthritis: an Unmet Need

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Despite major advances in axial spondyloarthritis and an increasing number of therapeutic options, questions remain related to the optimized treatment strategies and to the individual drug choice, according to a review published in Current Rheumatology Reports.

In this review, Denis Poddubnyy, Dr.Med., of Charité – Universitätsmedizin Berlin in Germany, summarizes the recent and expected developments related to the treatment of axial spondyloarthritis.

“Clinically relevant questions related to the choice of the best possible treatment strategy in an individual patient…include the choice of the first- and second-line drugs, criteria for treatment escalation and de-escalation, and the possibility of combination therapy,” wrote the authors. “Further clinical trials evaluating different treatment strategies not addressed so far are urgently needed.”

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally regarded as first-line pharmacological treatment for axial spondyloarthritis, but there are conflicting data on the safety of NSAIDs for axial spondyloarthritis in regard to cardiovascular side effects and mortality. While the continuous use of NSAIDs for two years in ankylosing spondylitis has been reported to slow radiographic progression compared with NSAID use only on demand, such a result has not been confirmed.

TNFi TREATMENT

For patients failing previous NSAID treatment, tumor necrosis factor inhibitors (TNFi) are an effective treatment, with five agents approved for use in the U.S. and Europe. An increasing number of interleukin (IL)-17 blocking agents show efficacy in axial spondyloarthritis including both non-radiographic and radiographic forms, with approvals granted for ixekizumab for both forms of disease, andsecukinumab for non-radiographicaxial spondyloarthritis. Potential therapeutic options foraxial spondyloarthritis include three Janus kinase inhibitors (JAKi), tofacitinib, filgotinib and upadacitinib, which have shown promising results in phase 2 studies of radiographic axial spondyloarthritis.

However, no information is available to identify patients who would respond to one of these three drug groups over another, and whether a combination of different targeted therapies would be effective in selected patients. Despite this, there is general agreement that early and long-term suppression of inflammation by TNFi can also retard radiographic progression, apart from in chronic ankylosing spondylitis, when radiographic progression is expected in the first two to four years. The results for the effects of IL-17i secukinumab on radiographic progression have been mixed, with trials ongoing.

TREAT-TO-TARGET

Treat-to-target recommendations for axial spondyloarthritis aim get the patient free of clinical and serological signs of disease activity and to prevent the structural damage. However, it is unknown whether a more strict and regulated treatment approach is superior to standard-of-care treatment regarding reaching remission and retardation of radiographic progression. An association between elevated C-reactive protein (CRP) or an elevation of the composite activity index ASDAS has been reported, as has an association between a reduction of the ASDAS with TNFi, but this assumed association has to be confirmed by controlled treat-to-target studies, which are underway.

While it is unknown which biologic is best for a single patient to treat musculoskeletal manifestations, predictors of a good response to TNFi include short symptom duration, or young age, and the presence of objective signs of inflammation such as elevated CRP and subchondral bone marrow inflammation on MRI, and perhaps HLA-B27. However, it is unknown whether these parameters also predict good responses to IL-17i and JAKi.

EARLY DIAGNOSIS

An early and correct diagnosis of axial spondyloarthritis is crucial for a successful therapy, but both under-diagnoses, with a gap between first symptoms and diagnosis of many years, and over-diagnosis are common. To address under-diagnosis, it is important that chronic back pain patients with a possible diagnosis of axial spondyloarthritis are referred to the rheumatologist. In primary care, all screening proposals apply to patients with chronic low back pain starting at an age younger than 45 years, combined with one or more parameters characteristic for axial spondyloarthritis such as inflammatory back pain or a positive HLA-B27. Meanwhile, positive MRI not so different from what is seen in axial spondyloarthritis has also been described in athletes as a cause of over-diagnosis, a problem linked to the increased number of patients referred with suspected axial spondyloarthritis. A false diagnosis may be avoided with a diagnostic rather than a classification approach, as it is more flexible and has to take into account the relative weight of single diagnostic parameter.

“There is still an unmet need for identification of patients in which the treatment can be safely discontinued,” the authors wrote.

Further studies are needed on whether the NSAID or the biologic should be reduced/stopped in patients responding well, especially in those being in remission, and how the reduction should be performed, taking risks and benefits into account. Meanwhile, data from studies assessing whether the dose of the biologic can be reduced without losing the status of remission are expected in the near future.

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REFERENCE

Denis Poddubnyy, Joachim Sieper. “Treatment of Axial Spondyloarthritis: What Does the Future Hold?”Current Rheumatology Reports.July 20, 2020. DOI https://doi.org/10.1007/s11926-020-00924-5