Background/Purpose: 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.
The aim of this study was 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); Comparator (continue with standard
dose of anti-TNF); Outcome (flare); and Study design (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 ³4 & Physician«s assessment ³4 or ÆBASDAI ³2. Exclusion
criteria were: less than 12 weeks on anti-TNF treatment before discontinuation
or no clinical improvement achieved during the treatment. Data were independently
extracted by two reviewers using a form developed for this purpose.

Results: Five studies out of 763 citations were included, with
a total of 220 patients (84% AS and 16% nr-axSpA). The study design was:
observational study 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). Sample size ranged between 17 and 111 patients and follow-up
period after discontinuation between 36 and 52 weeks. Data extracted for each
study are shown on the table. The percentage range of patients developing flare
during the follow-up period was 69-100%. Specifically, the percentage and corresponding
period for each study were as follows: 100% (within 36 weeks), 98% (within 48
weeks), and 69%, 79% and 79% (all three within 52 weeks). Median (range) time
to flare was 16 (6-24) weeks. Additionally, in 4 studies patients with flare were
re-treated later using the same anti-TNF. Overall, similar response to the one
achieved after the initial treatment was observed for most clinical outcomes.

Conclusion: 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.

Table: