Continued adalimumab treatment leads to superior outcomes in nonradiographic axSpa
Continued therapy with the tumour necrosis factor (TNF) inhibitor adalimumab appears to yield a higher rate of maintenance of remission in patients with nonradiographic axial spondyloarthritis (axSpa) as opposed to treatment withdrawal, according to the results of the ABILITY-3 study.
“However, a substantial proportion of patients can maintain drug-free remission following withdrawal of TNF inhibitor therapy after achievement of remission or low disease activity,” the investigators said.
“Accurate prediction of which patients can maintain drug-free remission is not currently possible, and not all patients who stop therapy and flare will be able to regain clinical remission after restarting treatment. The results of this study facilitate shared decision making between patients and physicians when cessation of TNF inhibitor therapy is under consideration for patients who are in remission,” they added.
ABILITY-3 initially included 673 adult patients with nonradiographic axSpa. Of these, 305 (45 percent; mean age 35 years; 62 percent male) had achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (<1.3) with open-label adalimumab—administered subcutaneously at a dose of 40 mg every other week for 28 weeks—from weeks 16 through 28.
Those patients with clinically remitted disease were then randomly assigned to 40-week, double-blind treatment with either adalimumab (continuation; n=152) or placebo (withdrawal; n=153). The primary efficacy endpoint of the proportion of patients who did not experience a flare (defined as ASDAS ≥2.1 at two consecutive visits) up to week 68 was markedly greater in the continuation group (70 percent vs 47 percent; p<0.0001). [Lancet 2018;392:134-144]
Significantly more patients in the withdrawal vs continuation group received rescue therapy with open-label adalimumab (44 percent vs 24 percent; p=0.0001). More than half (37 of 65; 57 percent) of patients in the former group regained ASDAS inactive disease with the 12-week rescue therapy.
Among 673 patients receiving adalimumab at any time, 77 percent reported an adverse event (AE) and 4 percent had a serious AE. Commonly reported AEs in both the adalimumab and placebo groups were nasopharyngitis, upper respiratory tract infection and worsening of axSpa.
“To our knowledge, ABILITY-3 is the first adequately powered study to evaluate the effect of TNF inhibitor treatment withdrawal in maintaining remission in the nonradiographic axSpa population,” the investigators pointed out.
Aside from facilitating shared decision making between patients and physicians when cessation of TNF inhibitor therapy is under consideration for patients who are in remission, the findings are said to advance the understanding of the under-characterized nonradiographic axSpa population and inform treatment recommendations.
Future studies are needed to identify which patients can or cannot maintain drug-free remission, the investigators said.
In a linked commentary, Dr Jürgen Braun from the Ruhr University Bochum in Germany wrote that the results of ABILITY-3 is important “because it shows, on the basis of appropriate methodology, that continuation of a TNF inhibitor has superior outcomes than discontinuation, and this was only true for patients who had reached a state of inactive disease after … TNF inhibitor therapy.” [Lancet 2018;392:98-100]
Braun emphasized, however, that stopping the drug in patients who are in remission remains an option, given the number of patients who withdrew treatment and remained in remission almost 10 months after.
“[W]ith almost 50 percent of patients achieving drug-free remission, the health system could possibly save a lot of money, but how this strategy would influence the future course of the disease is not known,” he said.