NCT01205854; Post-results.

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.

IMPORTANCE Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear.OBJECTIVE To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. DESIGN, SETTING, AND PARTICIPANTS ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. INTERVENTIONS Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). MAIN OUTCOMES AND MEASURESThe primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. RESULTSOf 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred.CONCLUSIONS AND RELEVANCE Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy.

ObjectiveTo investigate limiting factors of American College of Rheumatology (ACR)/EULAR Boolean remission in rheumatoid arthritis (RA), and compare patients who fulfil the criteria to patients who only partly fulfil the criteria, with respect to imaging inflammation and biologic disease modifying anti-rheumatic drug (DMARD) usage.MethodsPatients with DMARD-naïve RA were treated according to current recommendations in the the ARCTIC trial (Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen). Limiting factors of reaching ACR/EULAR Boolean remission at 2 years were assessed. Imaging inflammation (ultrasound and MRI) in patients in remission was compared with patients failing to fulfil different components of the criteria. The OR of biologic therapy was calculated using logistic regression.ResultsOf 203 patients, 112 (55%) reached ACR/EULAR Boolean remission; 49 (24%) fulfilled three of four criteria. The main limiting factors were patient global assessment (PGA) (59%) and tender joints (22%). Imaging inflammation was not significantly different for patients in remission and patients not fulfilling the criteria due to elevated PGA and/or tender joints, but higher odds of using biologics (OR 3.63, 95% CI 1.73 to 7.61) were observed.ConclusionsPGA and tender joints were the factors most often limiting achievement of ACR/EULAR Boolean remission. The level of imaging inflammation was not elevated in these patients compared with patients in remission, but the odds of using biologic DMARDs were higher.

Background:Remission is the preferred treatment target in rheumatoid arthritis (RA), and many patients require biologic DMARDs to reach this state. It is debated whether tapering of tumor necrosis factor inhibitor (TNFi) treatment to discontinuation should be considered in RA patients who sustain remission on treatment (1).Objectives:The primary study objective was to assess the effect of tapering and withdrawal of TNFi on the risk of flares in RA patients in clinical remission.Methods:In the non-inferiority ARCTIC REWIND trial, RA patients in remission for at least 12 months on stable TNFi therapy were randomly assigned to continued stable TNFi or tapering (half-dose TNFi for 4 months, thereafter withdrawal of TNFi), with visits every four months. csDMARD co-medication was kept stable in both arms. Patients had to be in DAS remission at inclusion with 0/44 swollen joints. The primary endpoint was the proportion of patients with disease flare during the 12-month study period (defined as DAS>1.6, change in DAS>0.6 and 2 or more swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Full-dose TNFi was reinstated in case of flares in the tapering arm. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. The inferiority null-hypothesis was tested in the per-protocol population by mixed effect logistic regression. Radiographs were scored by van der Heijde modified Sharp score (0 and 12 months, average of two readers, progression: ≥1 unit change). ClinicaltrialsNCT01881308.Results:We randomised 99 patients, 92 received the allocated treatment strategy, 84 were included in the per-protocol population. Baseline characteristics, clinical and ultrasound disease activity were balanced (Table). csDMARD co-medication was used by 93% in the stable and 88% in the tapering arm. In the primary analysis, 5% of patients in the stable TNFi arm experienced a flare during 12 months, compared to 63% in the tapering TNFi arm. The risk difference (95% CI) was 58% (42% to 74%, Fig 1), with stable treatment being deemed superior to tapering. 90% in the stable and 81% in the tapering arm did not show progression of radiographic joint damage, difference (95% CI) -9% (-24%, 6%). At 12 months, DAS scores, DAS remission and function were similar between groups (Fig 2). The numbers of adverse events (AE)/serious AE in the stable and tapering arm were 57/2 and 50/3, respectively, with 26 and 15 infections.Conclusion:In a randomised clinical trial assessing patients in prolonged and deep RA remission, we observed a large increase in the flare rate in patients who tapered and discontinued TNFi. Patients responded well to reinstated treatment and remission rates in the two study arms were comparable at 12 months.References:[1]Smolen et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. ARD 2020Table 1.Baseline values – n (%), mean (SD), or median (IQR)Stable, n=45Tapering, n=47Age, yrs57 (11)58 (13)Female30 (67%)25 (53%)ACPA+35 (78%)36 (77%)Symptom duration, yrs10 (7)12 (7)DAS0.9 (0.4)0.8 (0.3)CRP mg/L1 (1 – 2)1 (1 – 3)No ulttrasound power Doppler signal in any of 32 joints42 (96%)44 (94%)Disclosure of Interests:Siri Lillegraven: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga: None declared, Joe Sexton: None declared, Inge Olsen: None declared, Åse Lexberg: None declared, Tor Magne Madland: None declared, Hallvard Fremstad: None declared, Christian A. Høili Consultant of: Novartis, Gunnstein Bakland Consultant of: Novartis, UCB, Cristina Spada: None declared, Hilde Haukeland Consultant of: Novartis, Inger M. Hansen: None declared, Ellen Moholt: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Daniel Solomon Grant/research support from: Funding from Abbvie and Amgen unrelated to this work, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD