Background/Purpose: Tumour
Necrosis Factor alpha inhibitors (TNFi) have proven to be effective in the
treatment of with spondyloarthropaties. There is rationale to support that in
patients who have achieved disease remission while on treatment with TNFi, a
lower dose than that used to induce remission may suffice to maintain the
disease inactive in the long term. Dose reduction schedules are empirically
used in routine clinical practice, but up to now such practice is not based on
evidence from clinical trials. With the hypothesis that reduced doses are non
inferior to full doses in terms of maintenance of response and safety profile,
and with the aim to generate evidence to guide clinical practice, a
prospective, multicentre randomised open-label study with non-inferiority
objective was jointly sponsored by the Spanish Societies of Clinical
Pharmacology and Rheumatology.

Methods: A total of
126 patients with axial non-psoriatic spondyloarthritis that had been treated
with TNFi for a minimum of 12 weeks and had achieved a sustained clinical
remission (BASDI ≤ 2, no clinical arthritis or enthesitis
and normal CRP) during additional 8 weeks or more were randomized (1:1) to
continue with the full dose treatment (Control, C) or a reduced dose
maintenance treatment according to a standardized protocol (Experimental, E)
in 22 Spanish sites. The main study endpoint was the proportion of
patients who after 1 year qualified for Acceptable Therapeutic Goal (ATG)
(BASDAI, physician global assessment and patient and nocturnal axial pain VAS,
all <4). The non-inferiority design assumed 87% of ATG in the control group
and a lower limit for the 95%CI of the adjusted difference between treatments
of 17% for the per protocol (PP) population. The proportion of patients with
Ideal Therapeutic Goal (BASDAI, patient and physician global assessment, all
< 2) was a key secondary endpoint. Other endpoints included ASAS Disease
Activity Score, BASFI, and Quality of Life Questionnaire scores. Safety issues
with special focus on infectious adverse events were also evaluated. Patients
were visited every 8 weeks, following the recommendations of the Spanish
Rheumatology Society. Patients were followed a minimum of 56 weeks or until
treatment discontinuation. The study was registered with EudraCT: 2011-005871-18.

Results: Baseline
characteristics are described in table 1. In the PP population 48 (82.8%) patients in
the reduced arm and 47 (85.5%) patients in the full dose were on ATG at one
year assessment, with adjusted difference (95%CI) of -2.5%(-16.6 to 11.7%),
thus meeting the primary non inferiority study objective. The proportion of
infectious events were 17.2% in E and 25.5% in C groups (NS).

Table 1. Study results

Conclusion: This real-life study has shown that
optimization of TNFi treatment is non inferior to full TNFi doses in
maintaining Acceptable Therapeutic Goal after 1 year.

Funding: Funded by the Spanish Ministry of
Health (EC11-229)