Dose of TNF Therapy Can Be Lowered in Some Patients with Spondyloarthritis
by Dr. David Borenstein, MD Executive Editor TheSpineCommunity.com 1/2019
A common question from individuals with ankylosing spondylitis is “can the dose of my TNF inhibitor be reduced or discontinued if there is low disease activity?”
While Tumor Necrosis Factor (TNF) inhibitor antibodies have made control of the inflammation associated with ankylosing spondylitis (AS) possible, the question remains concerning the opportunity to lower or stop the drug and maintain a low disease activity state. Also, among the TNF inhibitors, Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Cimzia (certolizumab), or Simponi (golimumab) is one agent any better at achieving disease control at a reduced dose.
A small study from Spain tried to answer these important questions. The investigators screened 157 AS patients with 113 completing the study. These patients were in a low disease activity (LDA) as measured by less than 2 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), no clinical evidence of arthritis or tendonitis, and a normal C-reactive protein for 6 months or longer while taking the recommended dose of TNF inhibitor. A total of 55 AS patients remained on their full-dose TNF inhibitor, while 58 were placed on half dose therapy. The outcome of the study was the number of patients who remained in LDA at one year.
The results showed that 83.8% (47/55) of the full-dose group and 81.3% (48/58) reduced-dose group maintained LDA at 1 year. Treatment was discontinued in 4.8% (3/62) and 13.1% (8/61) full-dose and reduced-dose patients, respectively, for poor disease control. No specific TNF inhibitor was better at reaching LDA at a reduced dose. Serious infections were reported in 11.3% (7/62) assigned to the full dose and 3.3% (2/61) assigned to the reduced dose.
The results of this study suggest that once a LDA is achieved in an AS patient with a TNF inhibitor, the dose can be reduced while maintaining disease control and decreasing the risk of serious adverse events like infections. Individuals taking TNF inhibitors should not change their TNF dose, but discuss whether their situation is appropriate for a dosing change with their treating physician.
- Gratacos J et al: Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis. Arthritis Res Ther.
Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis
The objective was to determine if dose reduction is non-inferior to full-dose TNFi to maintain low disease activity (LDA) in patients already in remission with TNFi, in axial spondyloarthritis. Randomized, parallel, non-inferiority, open-label multicentre clinical trial. Patients were eligible if they had axial spondyloarthritis and had been in clinical remission for ≥ 6 months with any available TNFi (adalimumab, etanercept, infliximab, golimumab) at the dose recommended by product labelling. Patients were randomized by automated central allocation to continue the same TNFi dose schedule, or to reduce the dose by roughly half according to the protocol. The main outcome was the proportion of subjects with LDA after 1 year. Serious adverse reactions or infections were recorded. The trial stopped due to end of the funding period, after 126 patients were randomized; 113 patients (84.1% male, mean age (SD) 45.6 (13.0) years) were included in the main per-protocol subset. Non-inferiority was concluded for LDA at 1 year (47/55 (83.8%) patients in the full-dose and 48/58 (81.3%) patients in the reduced-dose arm, adjusted difference (95% CI) − 2.5% (− 16.6% to 11.7%)). Serious adverse reactions or infections were reported in 7/62 patients (11.3%) assigned to full dose and 2/61 patients (3.3%) assigned to reduced dose (p value = 0.164). In patients with ankylosing spondylitis in clinical remission for at least 6 months, dose reduction is non-inferior to full TNF inhibitor doses to maintain LDA after 1 year. Serious adverse events may be less frequent with reduced doses. EU Clinical Trials Registry, EudraCT 2011–005871-18 and ClinicalTrials.gov, NCT01604629 .