NEW YORK (Reuters Health)—In patients with active non-radiographic axial spondyloarthritis (nr-axSpA) who achieved remission while taking adalimumab, researchers saw fewer flares among those who continued taking the drug than among those who stopped taking it.
“The results showed that continued therapy with adalimumab was associated with a higher rate of maintenance of remission compared with treatment withdrawal,” the authors write in The Lancet, online June 28.1
The ABILITY-3 trial, led by Dr. Robert Landewe of Amsterdam Rheumatology & Clinical Immunology Center, enrolled adults in 20 countries with nr-axSpA who had objective evidence of active inflammation, active disease, and inadequate response to at least two non-steroidal anti-inflammatory drugs.
During the 28-week lead-in period, all 673 participants received 40 mg subcutaneous adalimumab every other week for 28 weeks. The 305 patients who achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) less than 1.3 at Weeks 16, 20, 24 and 28, were randomly assigned to 40 weeks of treatment with adalimumab or placebo.
Patients who experienced a flare (ASDAS 2.1 or higher at two consecutive visits) during the 40-week period received 12 weeks of rescue therapy with 40 mg open-label adalimumab every other week; original treatment allocation remained blinded.
More patients continuing adalimumab were free of flares (70% vs. 47%; P<0.0001) through Week 68.
Of the 673 patients who received adalimumab at any time, 516 (77%) reported an adverse event, and 28 (4%) reported a serious adverse event. The most common adverse events in both groups were nasopharyngitis, upper respiratory tract infection, and axSpA worsening.
Dr. Jurgen Braun of the Department of Rheumatology of Ruhr University Bochum in Germany tells Reuters Health by email, “I was a bit surprised about the high number of patients who were still in drug-free remission at the end of the observation period.”
“We need to know how many patients continue to be in remission after discontinuation and whether it is possible to predict who will not benefit from readministration,” adds Dr. Braun, who wrote an invited commentary about the study.2
“I think these results will make it easier to try the biologic and see whether it can be discontinued,” he says. “However, we will need to know more about the best time to discontinue and the clinical status of the patients at time of discontinuation, including magnetic resonance imagery and C-reactive protein values. We also need data on dose reduction strategies and studies in ankylosing spondylitis.”
“The main task for rheumatologists will remain to identify and treat axSpA patients in need for biologic therapy as early as possible,” Dr. Braun advises. “Some of them may have to be treated for a lifetime, for others it may be possible to reduce the dose, and for some it may even be possible to follow an on-demand strategy with intermediate discontinuation of therapy when ongoing remission is achieved.”
Dr. Fardina Malik, a rheumatologist in the Department of Medicine at NYU Langone Health in New York City, says by email, “Despite how happy patients are about achieving remission, they are always concerned about the side effects (e.g., malignancy risk, infections) and want to know if they can either taper or get completely off the medication once the axial SpA symptoms are under control.”
“But until now,” adds Dr. Malik, who also was not involved in the study, “we did not have data from randomized controlled trials to answer patients’ questions about their likelihood of flaring when they get off adalimumab.”
“These results might suggest the importance of treating patients aggressively early in their disease process (prior to development of radiographic disease) to achieve remission,” she notes. “I value and practice shared-decision making with my patients and feel more informed and certain about the risk of flare when they decide to discontinue after achieving remission.”
Dr. Malik adds that the findings “might be extrapolated to other TNF inhibitors,” and that “strengths of the study include its “large and adequate sample size, double-blind randomized design, clarity of statistical plan and description.”
But she adds that providers need to be cautious about applying these findings to patients of various races.
AbbVie funded the study. Most authors have financial relationships with the company.
References
- Landewé R, Sieper J, Mease P, et al. Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 2018 Jul 14;392(10142):134–144. doi: 10.1016/S0140-6736(18)31362-X. Epub 2018 Jun 29.
- Braun J. Discontinuing tumour necrosis factor inhibitors in non-radiographic axial spondyloarthritis. Lancet. 2018 Jul 14;392(10142):98–100. doi: 10.1016/S0140-6736(18)31440-5. Epub 2018 Jun 28.
