TNF Dose Reduction Succeeds in PsA, Axial Spondyloarthritis Save
Patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) who were doing well on treatment with tumor necrosis factor (TNF) inhibitors were able to successfully taper the therapy when guided by disease activity, a retrospective cohort study found.
Following a period of full-dose treatment during which a state of low disease activity was achieved, patients with PsA who tapered their treatment had a nonsignificant change in Disease Activity Score in 28 joints (DAS28) of 0.06 (95% CI -0.09 to 0.21), and also a nonsignificant difference of 0.03 (95% CI -0.14 to 0.20) during the subsequent year when they remained on the lower TNF inhibitor dose, reported Celia Michielsens, PhD, of Radboud Institute for Health Sciences in Nijmegen, The Netherlands, and colleagues.
Similarly, among patients with axSpA, the nonsignificant differences on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were 0.03 (95% CI -0.21 to 0.27) during the taper period and 0.05 (95% CI -0.24 to 0.34) during the post-taper phase, the researchers noted in the study online in Rheumatology.
Treatment with TNF inhibitors has been demonstrated to be safe and effective in these disorders, but use of these medications can have drawbacks, such as an increased risk of infection and high costs. In rheumatoid arthritis, disease activity-guided dose optimization has been shown to be both safe and effective (as well as cost effective), but thus far there has been a dearth of evidence for PsA and axSpA.
For more than a decade, a specific dose-tapering protocol has been used at Radboud Institute for not only rheumatoid arthritis, but also for PsA and axSpA, the authors said. The data on outcomes in this cohort has thus provided the team with a source for conducting a controlled retrospective study in a real-world setting to evaluate changes in disease activity and rates of flare and infections.
The analysis included 153 patients with PsA and 171 with axSpA treated between 2012 and 2018 who had been in a state of stable low disease activity for at least 6 months. Low disease activity was defined as a DAS28 below 2.4 in PsA and a BASDAI below 4 for axSpA. Tapering was accomplished by either lowering the dose of the TNF inhibitor or increasing the interval between doses in a prespecified manner.
Flare was defined as an increase of 1.2 points on the DAS28 for PsA and an increase of 2 or more points on the BASDAI. In the case of flare, patients were given glucocorticoids or nonsteroidal anti-inflammatory drugs (NSAIDs), with reassessment after a month. If the flare persisted, patients were then switched to a different TNF inhibitor or a different biologic or targeted synthetic agent.
Median follow-up among patients who underwent dose reduction was 46 months for the PsA group and 44 months for the SpA group.
Among the PsA patients, the mean DAS28 was 1.94 (95% CI 1.80-2.08) while on full dose (before taper); 2.0 (95% CI 1.89-2.11) in the tapering phase; and 1.97 (95% CI 1.86-2.09) in the stable dose post-taper phase.
For the axSpA patients, the corresponding mean BASDAI scores were 3.44 (95% CI 3.18-3.70), 3.47 (95% CI 3.19-3.74), and 3.48 (95% CI 3.19-3.78).
Mean percentages of the daily defined dose used, which was a secondary outcome, were 108% in the initial full-dose phase for PsA, decreasing to 62% in the tapering phase, and 78% in the post-taper phase. For axSpA, the mean percentages of daily defined dose were 108%, 62%, and 72%, respectively.
Among patients with PsA, the incidence of dose escalation for conventional disease-modifying antirheumatic drugs or glucocorticoids did not differ during or after tapering, while among the axSpA group, the use of glucocorticoid injections and NSAIDs was significantly lower during the taper and post-taper phase, Michielsens and co-authors reported.
In the PsA group, the incidence rate ratio for flares was numerically higher in the taper phase compared with the initial full-dose phase (1.25 vs 0.12, P=0.41), whereas for axSpA, the rate ratio was significantly lower in the taper phase (0.60, 95% CI 0.43-0.85, P<0.01).
No differences in infection rates were seen during the taper or post-taper phases for either group, the researchers said.
Among the PsA patients, 12% discontinued the TNF inhibitor in the taper phase, 61% of whom did not restart the treatment during follow-up. Among axSpA patients, 14% discontinued the TNF inhibitor, of whom 63% did not restart the treatment.
Study limitations, the investigators noted, included the open-label design and the possibility of nocebo effects and unmeasured confounding.
Nonetheless, "our study suggests that disease activity-guided dose optimization is effective and safe in PsA as well as axSpA," the team concluded. "However, in light of the limitations, more definite evidence should be provided by well-designed randomized prospective studies."
Source Reference: Michielsens C, et al "Tumor necrosis factor inhibitor dose adaptation in psoriatic arthritis and axial spondyloarthritis (TAPAS): a retrospective cohort study" Rheumatology 2021; doi:10.1093/rheumatology/keab741.