Disease Modifying Anti-rheumatic Drugs Tapering Research Articles

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial

Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. Research Council of Norway and South-Eastern Norway Regional Health Authority.

Treatment patterns of individualized real-life tapering approaches based on shared decision-making in rheumatoid arthritis.

To provide real-world evidence on patient-individual tapering patterns of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in daily clinical practice. Data obtained through acontrolled prospective cohort study in Germany conducted from July 2018 to March 2021 were analyzed. Participants consist of RA patients in sustained remission who were eligible for DMARD tapering at enrolment. Data from RA patients who experienced tapering of DMARDs at least once during the observational period (n = 200) were used. Descriptive analyses of medical outcomes at baseline and at time of first tapering, time to first tapering, tapering patterns by substance group, and tapering intensity were documented. We did not observe meaningful differences in either disease activity or quality of life measures between substance groups at enrolment, time of first tapering, and at 6or 12months after tapering. Median time until first tapering varied between substance groups (csDMARDs: 108days; bDMARDs: 189days; combination: 119days). Most patients received one iteration of tapering only (147/200patients, 73.5%). Dose reduction was applied for patients treated with csDMARDs (79/86patients, 91.8%), spacing of interval was the most frequent strategy for patients treated with bDMARDs only (43/48patients, 89.5%). Necessity for increased DMARD dosage was observed in only 10% of patients (20/200). Tapering intensity by substance was overall heterogenous, indicating high individualization. We identify highly heterogeneous tapering patterns between substance groups and within substances. Identification and recognition of patient-individual approaches of tapering will help to further improve the management of RA for both patients and rheumatologists.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for...

Tapering of disease-modifying antirheumatic drugs: an overview for daily practice.

In this Review, we discuss the possibility of drug tapering in patients with rheumatoid arthritis in remission or low disease activity, for glucocorticoids and disease-modifying antirheumatic drugs. We review international guidelines and recommendations, as well as remaining uncertainties, and provide an overview of the current literature. Three strategies of tapering are discussed: (1) tapering by discontinuation of one of the drugs in combination therapy regimens, (2) tapering by reducing the dose of one of the drugs in combination therapy regimens, and (3) tapering by dose reduction of monotherapy with disease-modifying antirheumatic drugs. We discuss the outcomes and robustness of evidence of trials and observational cohorts, and we give a trajectory for further research and drug tapering in daily practice.

Synovitis and Tenosynovitis on Ultrasound as Predictors of DMARD Tapering Failure in Patients with Long-Standing Rheumatoid Arthritis in Clinical Remission or Low Disease Activity.

This study aimed to investigate the predictive value of synovitis and tenosynovitis detected by grayscale (GS) and by power Doppler (PD) ultrasound (US) in relation to failure of tapering disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients. Long-standing RA patients who de-escalated treatment were included in this prospective cohort study. All patients underwent 3 ultrasonographic and clinical assessments, at baseline and every 3 or 4 months, over a period of 6-8 months. US investigation of 32 joints was performed. Synovitis was assessed by GS and PD semiquantitative scoring (0-3) and a global score was calculated for each individual by summing single joint scores. The presence of tenosynovitis was recorded whenever detected during ultrasound assessment. Thirty-three patients completed the follow-up period (29 women; 4 men). Eight patients (25%) relapsed. Using the optimal cutoff values determined by receiver operating characteristic curve, patients with a PD synovitis ≥1 at baseline had significantly greater chances to relapse than those without PD activity. During follow-up, GS tenosynovitis was detected in 6 patients (5 with PD) who failed and in 3 patients (1 with PD) who succeeded in tapering therapy. Having at least 1 joint with PD synovitis resulted in a relative risk of 3.14 and having GS tenosynovitis resulted in a relative risk of 11.4 (95% CI: 1.03-9.60 and 2.82-45.9, respectively) for relapse in the multivariate Poisson model. PD synovitis and GS tenosynovitis may be useful to identify RA patients in risk of relapse after DMARD tapering.

Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis

ObjectiveTo perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).MethodsThis is a systematic literature research of 2015–2018 publications on...

DMARD-free remission as novel treatment target in rheumatoid arthritis: A systematic literature review of achievability and sustainability

ObjectivesAlthough current treatment guidelines for rheumatoid arthritis (RA) suggest tapering disease-modifying anti-rheumatic drugs (DMARDs), it is unclear whether DMARD-free remission (DFR) is an achievable and sustainable outcome. Therefore, we systematically...