Tapering of tumor necrosis factor inhibitors is linked to more flares, lower remission rates than maintaining treatment at stable doses in patients with rheumatoid arthritis, study finds
Presenter: Kaja E. Kjørholt, Medical Doctor and PhD Fellow, Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway.
3-year results of tapering TNFi to withdrawal compared to stable TNFi among rheumatoid arthritis patients in sustained remission: A multicenter randomized trial. Abstract L07. Presented Nov 14, 2023.
As the debate continues over the appropriateness of a tapering-to-withdrawal strategy for tumor necrosis factor (TNF) inhibitor therapy in patients with rheumatoid arthritis (RA) in long-standing remission, results from a randomized trial presented at ACR Convergence 2023 suggest that doing so may be inferior to maintaining TNF inhibitor therapy at stable doses.
Patients with RA in remission for a year or more who tapered TNF inhibitor to withdrawal had more flares and lower remission rates when compared with those who maintained TNF inhibitor treatment at stable levels, according to data from the open-label randomized ARCTIC REWIND study.
“A large majority of RA patients in remission assigned to tapering TNF inhibitor to withdrawal experienced a flare within 3 years, while a minority of patients receiving stable TNF inhibitor treatment flared over the same time period,” said investigator Kaja E. Kjørholt of Diakonhjemmet Hospital, Norway.
“These findings do not support tapering of TNF inhibitor treatment among RA patients in sustained remission,” Kjørholt added.
Whether or not to taper TNF inhibitor treatment in patients with RA who reach sustained remission is debated in current guidelines, according to Kjørholt, who added that further data are needed to characterize the long-term consequences of tapering.
Accordingly, Kjørholt and colleagues conducted this open-label, multicenter, randomized study designed to assess the effect of tapering TNF inhibitor therapy in patients with RA who had already been in sustained remission for 1 year or more on stable dosing of TNF inhibitor therapy. The primary outcome was absence of a flare in disease activity over 3 years.
They defined a flare as a disease activity score (DAS) > 1.6, an increase in DAS of at least 0.6 units plus 2 or more swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Secondary outcomes of the study included remission (ACR/EULAR Boolean 2.0 and DAS), as well as adverse events and medication use.
A total of 99 patients were randomized and 92 received therapy; of those, 80 (87%) completed the 3-year follow-up. At baseline, the mean baseline DAS was 0.8 for the tapering TNF inhibitor group and 0.9 for the stable TNF inhibitor group. Most patients were also receiving conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (89% and 91% of the tapering and stable TNF inhibitor groups, respectively).
Results showed that only 25% of patients randomized to the TNF inhibitor tapering group remained flare-free for 3 years, as compared with 85% in the stable TNF inhibitor group (hazard ratio, 9.4; 95% confidence interval [CI], 3.9-22.8).
Among those patients who did flare, investigators reported, the majority in both groups were able to regain DAS remission by the next visit.
In the tapering group, they added, Boolean 2.0 remission rates were significantly lower compared with the stable group throughout the study period, with an adjusted risk difference over 36 months of minus 24% (95% CI, -33 to -15; P < .001). On the other hand, tapering was not associated with increased risk of switching to other types of biological DMARDs or using targeted synthetic DMARDs at the end of the study, Kjørholt said.
In addition, investigators did not observe any large differences in adverse events between the two groups. Adverse events were documented in 81% and 89% of the tapering and stable groups, respectively, while serious adverse events were seen in 21% in the tapering group and 11% in the stable group, the data show.
Taken together, these findings support that most RA patients in remission benefit from continuous TNF inhibitor therapy to maintain remission and minimize the risk of disease flare.
However, shared decision making should be central when treating RA patients in sustained remission, Kjørholt emphasized.
“The patients should be informed about the potential disadvantages of tapering, but the overall situation of the patient, including any adverse events and the patient’s own preferences, should be taken into account when deciding the treatment strategy,” Kjørholt said.
Disclosures:
ARTIC REWIND was supported by the Research Council of Norway and South-Eastern Norway Regional Health Authority. Kaja E. Kjørholt reported no financial disclosures related to this presentation.
Reference:
Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017; 76(6):960-977. doi:10.1136/annrheumdis-2016-210715