Objective. Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy.Methods. The study was designed as a pragmatic multicenter, open-label randomized controlled trial. Inclusion criteria were a diagnosis of RA according to the American College of Rheumatology 1987 classification criteria, as well as use of a TNFi for at least 1 year along with a stable dose of disease-modifying antirheumatic drugs and a Disease Activity Score in 28 joints (DAS28) of <3.2 over the 6 months preceding trial inclusion. Patients were randomized in a 2:1 ratio to either stop or continue treatment with their current TNFi. Flare was defined as a DAS28 of ‡3.2 during the 12-month follow-up period and an increase in score of ‡0.6 compared to the baseline DAS28.Results. In total, 531 patients were allocated to the stop group and 286 to the TNFi continuation group. At 12 months, more patients had experienced a flare in the stop group (272 [51.2%] of 531) than in the continuation group (52 [18.2%] of 286; P < 0.001). The hazard ratio for occurrence of a flare after stopping TNFi was 3.50 (95% confidence interval [95% CI] 2.60-4.72). The mean DAS28 in the stop group was significantly higher during the followup period compared to that in the continuation group (P < 0.001). Of the 195 patients who restarted TNFi treatment after experiencing a flare and within 26 weeks after stopping, 165 (84.6%) had regained a DAS28 of <3.2 by 6 months later, and the median time to a regained DAS28 of <3.2 was 12 weeks (95% Cl 10.7-13.3). There were more

ObjectiveSuccessfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment.Methods439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression.ResultsAt baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30−44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had ≥1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00–3.40), DMARD escalation (OR = 1.99, 95% CI 1.01–3.94) and physician-reported flare (OR = 2.00, 95% 1.06–3.77).ConclusionFor RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.

Although an official WTA is not defined, the mean saved cost of €368,269 per QALY lost seems acceptable in The Netherlands, given existing data on willingness to pay.

In RA patients with longstanding low disease activity, at time of stopping TNFi, US is a predictor for flare at group level, but at the patient level, US has limited added value when common clinical parameters are used already, though the predictive value of clinical predictors is modest as well.

Stopping TNFi had a significant negative short-term impact on a broad range of PROs. Long-term negative consequences appeared to be limited, and outcomes in patients needing to restart TNFi within the first 6 months tended to be restored at 12 months.

Background The aim of this study was to identify predictors of prolonged disease control after discontinuation of tumor necrosis factor inhibitor (TNFi) treatment in patients with rheumatoid arthritis (RA). Methods Post-hoc analysis of 439 RA patients (67.3% rheumatoid factor positive) with longstanding RA in remission or with stable low disease activity, randomized to stopping TNFi treatment in the multicenter POET trial. Prolonged acceptable disease control was defined as not restarting TNFi treatment within 12 months after stopping. Baseline demographic and disease-related variables were included in univariate and multivariate logistic regression analysis for identifying predictors of relapse. Results One year after baseline, 220 patients (50.1%) had not restarted TNFi treatment. Use of an anti-TNF monoclonal antibody (versus a receptor antagonist, OR = 2.41; 95% CI: 1.58–3.67), ≤10 yrs. disease duration (OR = 2.15; 95% CI: 1.42–3.26) and low or moderate multi-biomarker disease activity (MBDA) scores (OR = 2.00; 95% CI: 1.10–3.64) at baseline were independently predictive of successful TNFi discontinuation (area under the receiver operating characteristic curve = 0.66; 95% CI: 0.61–0.71). Results were similar when using no physician-reported flare as the criterion. TNFi-free survival was significantly different for patient groups based on the number of predictors present, ranging from 21.4% of patients with no predictor present to 66.7% of patients with all three predictors present. Conclusion Patients using an anti-TNF monoclonal antibody, with shorter disease duration and low or moderate baseline MBDA score are most likely to achieve prolonged disease control after TNFi discontinuation. Trial registration Netherlands Trial Register NTR3112 , 21 October 2011. Electronic supplementary material The online version of this article (10.1186/s41927-019-0071-x) contains supplementary material, which is available to authorized users.

BackgroundThe effectiveness of TNF-inhibitors (TNFi) in the treatment of rheumatoid arthritis has been demonstrated in many studies [1]. However, little is known on stopping TNFi in patients with stable low disease activity and the subsequent likelihood of exacerbation of rheumatoid arthritis (RA). In addition, it is not clear whether TNFi can be restarted effectively and safely. Given the costs and risks [2], it is important to examine whether patients in stable low disease activity can effectively stop TNFi.ObjectivesTo assess whether RA-patients in stable remission or low disease activity (DAS28<3.2) can effectively and safely stop and restart TNFi.MethodsMulticenter open-label randomized controlled trial. Patients diagnosed with RA according to the ACR 1987 criteria were included. Patients had been treated with a TNFi for at least 1 year and with stable dose DMARDs for at least 6 months. All included patients had low disease activity in the 6 months prior to inclusion, with at least 2 DAS28 scores <3.2 in this period. Patients were randomized to stop or continue their current TNFi in a 2:1 ratio. DAS28 flare was defined as DAS28 ≥3.2 with an increase ≥0.6 compared to the previous DAS28.ResultsIn total 817 patients from 47 centers were included: 531 (65%) patients were randomized to the stop group and 286 (35%) to TNFi continuation. All included patients had low disease activity in the 6 months prior to inclusion, with at least 2 DAS28 scores <3.2 in this period and 81.1% was in remission (DAS28<2.6). At 6 months, significantly more patients in the stop group had experienced a DAS28 flare versus the continuation group (29.3% vs 9.7% respectively, p<0.0001). At 12 months these were 40.8% vs 14.4% respectively, p<0.0001. Flare free survival was significantly lower in the stop group (p<0.0001), with a median time to first flare of 24 weeks in those that flared. The adjusted hazard ratio for flare after stopping TNFi was 3.19 (95% CI: 2.26–4.50). Of the patients that restarted TNFi within the first 26 weeks after stopping, already 83% had regained DAS28<3.2 six months later and median survival time to regained DAS28<3.2 was 12 weeks (95% Cl 10.9-13.1).Conclusions59% of RA-patients with stable remission or low disease activity (DAS28 <3.2) can stop TNFi without flare in 12 months follow up. The data suggest that TNFi can be restarted effectively and safely.ReferencesNam JL, Winthrop KL, van Vollenhoven RF, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 2010;69:976–86.Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic and biological DMARDs – a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2013; submitted.Disclosure of InterestNone declared

These results support the use of composite disease activity indices, patient-reported pain and disease activity, and physician-reported disease activity for measuring disease exacerbation or identifying flares of RA. Physical function, acute-phase response, and the auxiliary measures fatigue, participation, and emotional well-being performed poorly.