Antitumor necrosis factor (anti-TNF) therapy does not always inhibit radiographic progression in axial spondyloarthritis (axSpA). In addition to injection site irritation, it is associated with adverse effects including serious microbial infection and, in long-term use, oncogenesis. It is also costly. These issues have led researchers and clinicians to consider whether anti-TNF therapy for axSpA might be tapered or discontinued in those with stabile disease.

A multicenter team of Spanish researchers found that although tapering of anti-TNF therapy can facilitate sustained remission or lower disease activity in patients, abrupt discontinuation of therapy results in disease flares and should be avoided.1



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The research team, headed by Victoria Navarro-Compán, MD, of the University Hospital La Paz in Madrid, conducted a systematic literature review, searching Medline, EMBASE, and Cochrane databases, to assess anti-TNF therapy discontinuation and tapering strategies for axSpA.

Specifically, they identified studies in which low disease activity or clinical remission was achieved after a course of standard-dose anti-TNF therapy. Outcomes for discontinuation and tapering were evaluated separately, and the studies were rated for quality and potential biases on a 5-point scale according to Oxford Levels of Evidence guidelines.

Of 763 study citations retrieved, 13 met the study criteria, leading the researchers to comment that published data on tapering and discontinuation strategies for patients with axSpA are scarce. They also noted that the level of evidence is weak.

Of 5 studies assessing discontinuation of anti-TNF therapy, 4 were observational and only 1 was a randomized controlled trial (RCT). The level of evidence was rated as 4 (case series and poor-quality cohort/case-control studies) for all 5 studies. Of 8 studies assessing tapering, 6 were observational (3 retrospective and 3 prospective), 1 was an interventional nonrandomized trial, and 1 was an interventional RCT. The level of evidence was rated as 4 for all of the studies but one, which was rated as 2b (individual cohort study/low-quality RCT).

In the 5 studies that assessed discontinuation strategies, the authors identified 220 patients who had been treated with etanercept, infliximab, or adalimumab. The researchers found that when therapy was discontinued, disease flares occurred in 76% to 100% of patients during the follow-up period (median 52 weeks; range 36-52 weeks). The median time to flare for these patients was 16 weeks (range 6-24 weeks). In most of the studies, flares were defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4 and physician assessment of disease activity score ≥ 4 or an increase in BASDAI score ≥ 2 points.

The individual populations of the 8 tapering-assessment studies ranged from 8 participants to 136 participants. Rather than providing a total pooled patient population, Navarro-Compán and colleagues reported a median of 43 patients. Anti-TNF regimens used included etanercept, infliximab, adalimumab, or combination etanercept/infliximab. Dose reduction was most frequently accomplished by lengthening the time between drug doses rather than by decreasing the dose of the injection or infusion of the therapeutic agent.

In 5 of the 8 tapering-assessment studies, lower disease activity or remission was maintained in 53% to 100% of patients. The remaining 3 studies assessed mean change in BASDAI and C-reactive protein (CRP) level after reduction of anti-TNF drug dose and found no relevant increase in either. Remission was most often defined as BASDAI < 2 and normal CRP level and low disease activity was most often defined as BASDAI < 4 and normal CRP level.

Dr. Navarro-Compán and colleagues concluded that tapering of anti-TNF regimens could have a significant impact on ameliorating adverse effects and expense of therapy without compromising patient health in axSpA; however, they stressed that further, more comprehensively designed studies are required to confirm their findings as are studies that identify which patients will not benefit from tapering strategies and why.

Summary and Clinical Applicability

In summary, in those patients with axSpA in remission or with low disease activity, tapering of anti-TNF therapy is feasible and can facilitate sustained remission or keep disease activity low in most patients.Abrupt discontinuation of therapy, however, should be avoided because disease flares can be expected.

Limitations and Disclosures

This study was limited by the small number of published studies that met inclusion criteria and the poor quality of the data in those studies, virtually all of which was rated as 4 per Oxford Levels of Evidence guidelines. Additionally, more comprehensively designed studied are needed. 

Nevertheless, the findings suggest that tapering of anti-TNF regimens may ameliorate the risk for adverse effects and the expense of anti-TNF therapy without the risk for flares in those with axSpA.

References

1. Navarro-Compán V, Plasencia-Rodríguez C, de Miguel E, et al. Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. Rheumatology (Oxford). 2016  [Epub ahead of print March 21,2016]  doi:10.1093/rheumatology/kew033