Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial

Abstract

ObjectivesTo evaluate the 2-year clinical effectiveness of two gradual tapering strategies. The first strategy consisted of tapering the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) first (i.e., methotrexate in ~90%), followed by the tumour necrosis factor inhibitor (TNF-inhibitor), the second strategy consisted of tapering the TNF-inhibitor first, followed by the csDMARD.MethodsThis multicentre single-blinded randomised controlled trial included patients with rheumatoid arthritis (RA) with well-controlled disease for ≥3 consecutive months, defined as a Disease Activity Score (DAS) measured in 44 joints ≤2.4 and a swollen joint count ≤1, which was achieved with a csDMARD and a TNF-inhibitor. Eligible patients were randomised into gradual tapering the csDMARD followed by the TNF-inhibitor, or vice versa. The primary outcome was the number of disease flares. Secondary outcomes were DMARD-free remission (DFR), DAS, functional ability (Health Assessment Questionnaire Disability Index (HAQ-DI)) and radiographic progression.Results189 patients were randomly assigned to tapering their csDMARD (n=94) or TNF-inhibitor (n=95) first. The cumulative flare rate after 24 months was, respectively, 61% (95% CI 50% to 71%) and 62% (95% CI 52% to 72%). The patients who tapered their csDMARD first were more often able to go through the entire tapering protocol and reached DFR more often than the group that tapered the TNF-inhibitor first (32% vs 20% (p=0.12) and 21% vs 10% (p=0.07), respectively). Mean DAS and HAQ-DI over time, and radiographic progression did not differ between groups (p=0.45, p=0.17, p=0.8, respectively).ConclusionThe order of tapering did not affect flare rates, DAS or HAQ-DI. DFR was achievable in 15% of patients with established RA, slightly more frequent in patients that first tapered csDMARDs. Because of similar effects from a clinical viewpoint, financial arguments may influence the decision to taper TNF-inhibitors first.

The number of risk factors for persistent disease determines the clinical course of early arthritis

“…In the future, DFR rates might also be influenced by the ongoing debate on the definition of remission and which criteria should be used when tapering of medication is considered. Current EULAR recommendation recommend to taper medication in patients who are in persistent (Boolean) remission, while none of the current tapering trials used this definition [ 8 , 25 , 26 ]. The Boolean remission criteria are more stringent than the DAS-based criteria (DAS < 1.6).…”

“…If tapering is only commenced in patients who are in Boolean remission, than fewer patients are able to taper medication and subsequently reach DFR, but this might also lead to less disease flares during tapering. However, recently, van Mulligen et al [ 25 ] showed that flare rates during tapering were similar for patients who were and were not in Boolean remission. On the other hand, the chance at a flare, while in DFR, diminishes with time and when patients are >1 year in DFR, this chance is <5%, which emphasizes the importance of reaching SDFR [ 27 ].…”

Correspondence on ‘Tapering towards DMARD-free remission in rheumatoid arthritis‘

“…We believe that the article 'Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial' by Mulligen et al, 1 is of great interest since it addresses important information on the gradual reduction of treatment in patients with rheumatoid arthritis (RA), to achieve disease-modifying antirheumatic drug (DMARD)-free remission (DFR). However, we would like to highlight and complement the importance of some potentially relevant points, and broaden the horizon and the approach to a topic of such complexity: 1.…”

“…2. The authors mentioned in their discussion that 30% of the group that initially decreased conventional synthetic DMARD (csDMARD) and 45% of the group that first decreased the TNFinhibitor (TNFi) were not on monotherapy 1 ; therefore, at the time of remission, they were still treated with some other DMARD, thus precluding absolute results of sustained remission free of DMARD, the study's main objective. Comparing the characteristics of patients only on monotherapy would be desirable.…”

“…These results led to modifications in the DMARD dose to decrease the risk of exacerbations. Due to the polyarticular characteristics of the disease, it is difficult to consider that patients only have one inflamed joint at the time of DFR, but they were included following the selection criteria in the article by Mulligen et al 1 ; the lack of power Doppler ultrasonography precludes the definite lack of more inflamed joints and increases the probability of exacerbations.…”