Background In patients with axial spondyloarthritis (axSpA), anti-TNF therapy is successful for clinically improving signs and symptoms of the disease. However, there is no clear evidence of the capability of this therapy to slow or inhibit radiographic progression. Based on this, it is unclear whether or not this treatment should be indefinitely sustained once the clinical goal is achieved in these patients.
Objectives To evaluate if discontinuation of anti-TNF therapy is successful to maintain clinical response in patients with axSpA.
Methods A systematic literature review until August 2014 was performed using Medline, EMBASE and Cochrane databases. The research question was formulated according to the PICOS method: Population (axSpA patients); Intervention (discontinuation of anti-TNF); Outcome (flare); and Setting (longitudinal studies with at least 6 months of follow-up after anti-TNF discontinuation). Flare was assessed according to the definition employed by each study, usually BASDAI ≥4 & Physician's assessment ≥4 or ΔBASDAI ≥2. Exclusion criteria were: less than 12 weeks on anti-TNF treatment before discontinuation or no clinical improvement achieved during the treatment. Data was extracted using a form developed for this specific purpose. Results are shown as median (range) and relative frequencies in percentages.
Results Five studies from 763 citations were included, with a total of 215 patients (76% AS and 24% nr-axSpA). The study design was: prospective observational studies following participation on a RCT (n=4) and RCT (n=1). In these studies, patients receiving standard doses of an anti-TNF drug discontinued this therapy and were followed in order to assess the appearance of flare. Discontinued therapy was etanercept (n=3), infliximab (n=1), and adalimumab (n=1). The characteristics of the studies were: total number of patients 42 (24-111) and follow-up period after discontinuation 52 (36-52) weeks. Baseline characteristics of patients were: age 39 (37-40) years old, 68% (45-77) males, disease duration 8 (3-15) years, 92% (67-100) HLA-B27+, and time receiving anti-TNF therapy before discontinuation 11 (2.5-36) months. Median (range) percentage of patients developing flare during the follow-up period was 79% (69-100). Specifically, these percentages and periods were as follows: 100% (within 36 weeks), 98% (within 48 weeks), and 69%, 79% and 79% (within 52 weeks). Median (range) time to flare was 16 (6-24) weeks. Furthermore, the 4 observational studies following a RCT re-treated patients with flare using the same anti-TNF. Overall, similar response to the one achieved at the beginning of the RCT was observed for most clinical outcomes.
Conclusions Published data indicates that discontinuation of anti-TNF therapy in patients with axSpA leads to the appearance of flare within a few months in most cases. However, most of the published evidence is based on studies including patients with established disease. Therefore, it still remains to be evaluated whether or not this high frequency of flares is observed in patients with shorter disease duration.
Disclosure of Interest None declared