V. Rantalaiho

Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial.

IntroductionEarly treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs (DMARDs) or a single DMARD.MethodsA cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug-treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years.ResultsSixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P = 0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years.ConclusionsTargeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy.Trial registrationCurrent Controlled Trials ISRCTN18445519.

The good initial response to therapy with a combination of traditional disease-modifying antirheumatic drugs is sustained over time: the eleven-year results of the Finnish rheumatoid arthritis combination therapy trial.

OBJECTIVE To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission. RESULTS At 11 years, 138 patients were assessed (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/-SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination-DMARD group and the single-DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively. CONCLUSION Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single-DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.

Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-onset Still's Disease. An Open, Randomized, Multicenter Study

Objective. To study the efficacy of anakinra versus disease-modifying antirheumatic drugs (DMARD) in refractory adult-onset Still’s disease (AOSD). Methods. In a 24-week study, 22 patients with AOSD taking prednisolone ≥ 10 mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was achievement of remission. Results. At 8 and 24 weeks, 7/12 and 6/12 receiving anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced greater improvement in physical health measured by Medical Outcomes Study Short-Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks, 7/14 patients taking anakinra and 2/3 taking DMARD were in remission. Conclusion. Anakinra induced more beneficial responses than DMARD in patients with AOSD and was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration NCT01033656).

Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial

Objective To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis (RA). Methods Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and with prednisolone (7.5 mg/day), and randomised to double blindly receive either infliximab (3 mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 5 years the clinical and radiographic outcomes were assessed. Results Ninety-one patients (92%) were followed up to 5 years, 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups. At 5 years, the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60% (95% CI 44% to 74%) and 61% (95% CI 45% to 75%) (p=0.87), and 84% (95% CI 71% to 94%) and 89% (95% CI 76% to 96%) (p=0.51). The corresponding mean (SD) total Sharp/van der Heijde scores at 5 years were 4.3 (7.6), and 5.3 (7.3), while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 (95% CI 0.0 to 3.4) and 3.7 (95% CI 2.2 to 5.8) (p=0.13). Conclusions In early RA, targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years; adding initial infliximab for 6 months does not improve these outcomes.

Decline in work disability caused by early rheumatoid arthritis: results from a nationwide Finnish register, 2000–8

Objectives To study whether the work disability (WD) rates in early rheumatoid arthritis (RA) have changed in Finland, where the treatment of RA has long been active but has intensified further since 2000. Methods All incident non-retired patients with RA of working age (18–64 years) in a nationwide register maintained by the Finnish Social Insurance Institution from 1 January 2000 to 31 December 2007 were identified. Patient cohorts were analysed in 2-year time periods (2000–1, 2002–3, 2004–5, 2006–7) and initial disease-modifying antirheumatic drugs (DMARDs) were elucidated from the drug purchase register. The incidence of continuous WD in the RA cohorts as well as in the entire Finnish population up to 31 December 2008 was analysed. Results A total of 7831 patients were identified (71% women, 61% rheumatoid factor-positive). Throughout the follow-up period the use of methotrexate and combination DMARDs as the initial treatment of early RA increased. During the first 2 years the incidence of RA-related continuous WD was 8.9%, 9.4%, 7.2% and 4.8% in the year cohorts, respectively (p<0.001 for linearity). Compared with the entire Finnish population, the age- and sex-stratified standardised incidence ratio of a WD pension due to any cause was 3.69, 3.34, 2.77 and 2.80 in the year cohorts, respectively (p<0.001 for linearity). Conclusions Since 2000 the frequency of continuous WD in early RA has declined in Finland. The present data allow no explanatory analysis but, at the same time, increasingly active treatment strategies have been introduced.

Physicians' adherence to tight control treatment strategy and combination DMARD therapy are additively important for reaching remission and maintaining working ability in early rheumatoid arthritis: a subanalysis of the FIN-RACo trial

Ample evidence shows that both monitoring disease activity and aiming at remission,1–4 as well as using combinations of disease modifying antirheumatic drugs (DMARDs), are effective treatment strategies in early rheumatoid arthritis (RA).5–8 Still, some authorities stress the former, but ignore the latter.9 In the FIN-RACo trial, 195 patients with early, active RA were randomised for a 2-year treatment with either a triple-combination of DMARDs and prednisolone (FIN-RACo) or DMARD monotherapy and discretionary prednisolone (SINGLE); both drug treatment strategies aimed at strict remission.6 Thus, in case of active disease, all inflamed joints had to be injected with glucocorticoids and predefined DMARD treatment adjustments made. After 2 years, remission was more common in the FIN-RACo than in the SINGLE group (37% vs 18%), and in a multivariate analysis only the treatment strategy proved to predict remissions at 2 years.6 Further, at 5 years, work disability (WD) was less common in the FIN-RACo than in the SINGLE group, especially regarding the patients who had reached remission at 6 months.10 In these subanalyses we wanted to study separately the roles of targeted treatment and combination DMARD …

Patient-reported outcomes as predictors of remission in early rheumatoid arthritis patients treated with tight control treat-to-target approach

Identifying prognostic factors for remission in early rheumatoid arthritis (ERA) patients is of key clinical importance. We studied patient-reported outcomes (PROs) as predictors of remission in a clinical trial. We randomized 99 untreated ERA patients to receive remission-targeted treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months, and infliximab or placebo for the initial 6 months. At baseline, we measured following PROs: eight Short Form 36 questionnaire (SF-36) dimensions, patient’s global assessment [PGA, visual analogue scale (VAS)], Health Assessment Questionnaire (HAQ), and pain VAS. We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years. Follow-up data at 2 years were available for 93 patients (92%), and 58 patients (62%) were in remission. At baseline, patients who achieved remission had higher radiological score (p = 0.04), lower tender joint count (p = 0.001), lower PGA (p = 0.005) and physician’s global assessment (p = 0.019), lower HAQ (p = 0.016), less morning stiffness (p = 0.009), and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not. In multivariable models that included all PROs, remission was associated with SF-36 dimensions higher vitality (odds ratio 2.01; 95% confidence interval 1.19–3.39) and better emotional role functioning (odds ratio 1.64; 95% confidence interval 1.01–2.68). PGA, pain VAS, HAQ, and other SF-36 dimensions were not associated with remission. We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA.

Alternative interpretation of data for recommendations on how to manage rheumatoid arthritis

This letter is inspired by the ‘EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update’.1 There is no question that we are in full agreement with the overarching principles of the EULAR recommendations. What goes against our principles, however, is the tone of the bullet points. …

THU0119 Impact of Neglecting Intra-Articular Glucocorticoid-Injections in Remission Targeted Treatment of Early Rheumatoid Arthritis

Background Intra-articular glucocorticoid-injections (IACIs) have been used widely for decades in the treatment of rheumatoid arthritis (RA). However, very limited amount of data exist on their impact (1). Objectives We aimed to study the effects of missing IACIs in otherwise intensively treated early RA patients. Methods 99 patients with active early RA were enrolled into a investigator-initiated, randomized, double-blind, trial, the NEO-RACo trial. They were treated with an intensified combination of methotrexate, sulfasalazine, hydroxychloroquine, low-dose prednisolone, and IACIs for 2 years, and randomized to receive either infliximab or placebo for the initial 6 months. At all times, treatment was targeted to modified American College of Rheumatology (ACR) remission and according to protocol IACs had to be given to every swollen joint as well as drug doses increased, if RA was active. Patients were assessed clinically 11 times during the first 12 months and thereafter every three months. Quality of life was assessed with the Short-Form 36 questionnaire at 0, 8, 12 and 24 months. Radiographs of the hands and feet were taken at baseline and at 24 months. Retrospectively, patients were scored at each of the 15 study visits 0.2 points if 1–2 small swollen joints were not given IACIs, and 0.4 points if >2 small or ≥1 large swollen joints were not injected. However, points were not given if at least 2 ml of glucocorticoid suspension (methylprednisolone or triamcinolone hexacetonide) per visit were used. Patients were divided into tertiles according to their cumulative score for missed injections (CSMI) and linear trend between the tertiles was tested. Results At 24 months, higher CSMI was associated with lower DAS28 (p=0.021) and strict remission rates (p=0.005), and higher DAS28 AUC (p<0.001). At 24 months, DAS28 remission rates were 90%, 93% and 76% in tertiles of CSMI (p=0.081), and strict remission rates were 74%, 77% and 39% in tertiles of CSMI (p=0.005). Quality of life was lower in the third tertile than in the first (p<0.001) and the second tertiles (p=0.020). No significant differences were observed in radiological progression. Conclusions Neglecting IACIs into swollen joints is associated with higher disease activity over time, lower remission rates and lower quality of life in early RA. Hence, IACIs should be used as an integral part of the targeted treatment of early RA. References Furtado RN, Oliveira LM, Natour J. Polyarticular corticosteroid injection versus systemic administration in treatment of rheumatoid arthritis patients: a randomized controlled study. J Rheumatol 2005 Sep;32(9):1691-1698. Leirisalo-Repo M, Kautiainen H, Laasonen L, Korpela M, Kauppi MJ, Kaipiainen-Seppanen O, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis 2013 Jun;72(6):851-857. Acknowledgements The authors would like to thank all participating patients, study nurses, and co-investigators. Disclosure of Interest None declared

Changing sulphasalazine to methotrexate does not improve the 2-year outcomes of the initial single DMARD treatment in early rheumatoid arthritis: subanalysis of the FIN-RACo trial

The current treatment of rheumatoid arthritis (RA) aims at early and sustained remission.1 However, the opinions on how to reach this target vary. The European guideline recommends the use of initial methotrexate (MTX), and if that fails, adding a biologic. A combination of disease modifying antirheumatic drugs (DMARDs) is not seen as an option as initial therapy or as the next step in patients with active RA failing MTX.2 Others have, however, included combination DMARDs in the first and second line treatment recommendations,3 ,4 and the Finns, thanks to the encouraging results and comprehensive national participation in the FIN-RACo trial,5 even propose triple DMARD combination as the initial treatment in active early RA.6 Direct comparisons between combination therapy and single MTX have been lacking; until recently, the tREACH trial fulfilled this gap by confirming the superiority of triple combination compared with single MTX in early RA.7 The FIN-RACo trial proved that the initial triple DMARD combination (MTX, sulphasalazine (SASP) and hydroxychloroquine) is superior to single DMARD therapy, started with SASP, which, however, could be …