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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 therapy on remission rates and WD days in early RA according to the participating physicians’ adherence (n=29) to follow the predefined study protocol. To study this, we scored each of the nine study visits between 0 and 24 months according to the following method: 0.4 points if the patient had an inflamed joint but glucocorticoid was not injected; 0.4 points if the disease was active but the DMARD treatment was not modified; and 0.2 points if the study forms were inadequately filled in. Thus, the maximum score for the physician's ‘inactivity’ was 1 point/visit, and 9 points for the whole follow-up. According to the median value of ‘inactivity’ we assigned the treatment as active (ACT) (<4 points) or non-active (non-ACT) (≥4 points), and formed four groups of the patients; 1: FIN-RACo+ACT, 2: FIN-RACo+non-ACT, 3: SINGLE+ACT and 4: SINGLE+non-ACT, and analysed the strict remission rates at 6, 12 and 24 months as well as the cumulative WD days up to 5 years in these four subgroups.
A total of 178 patients (91%) were followed up for 2 years. The remission rates at 6, 12 and 24 months are presented in figure 1. In a logistic regression analysis for the odds of being in remission at 2 years, only FIN-RACo treatment (OR 2.8, 95% CI 1.4 to 5.5) and physician's activity (OR 2.3, 95% CI 1.2 to 5.0) were significant, and had an additive effect (OR 3.4, 95% CI 1.2 to 9.5), while age, sex, rheumatoid factor positivity or baseline disease activity had no predictive value. Furthermore, the mean (SD) baseline disease activity score assessing 28 joints had been similar in patients consequently treated actively (5.55 (0.99)) or inactively (5.58 (1.06)) (p=0.40). For the 162 patients working or available to work at baseline, the numbers of cumulative WD days during 5 years were 222 in group 1, 470 in group 2, 491 in group 3 and 650 in group 4 (age and sex adjusted p<0.001) (figure 2).
These subanalyses show that in early RA targeted treatment and combination DMARDs are equally and additively important for reaching remission and maintaining work ability. The best results are achieved in patients treated actively with combination DMARDs, while the patients treated conservatively with a single DMARD have the worst outcomes. Treating the patients actively with a single DMARD gives as good (or poor) results as treating them inactively with combination DMARDs. Thus, using targeted treatment with monotherapy may well substitute for using combination DMARDs, but to benefit as many early RA patients as possible both approaches are necessary.
Contributors All authors contributed to the conception and design of the study and participated in the analysis and interpretation of the data. VR drafted the article and the other authors revised it critically for intellectual content. All authors approved the final version of this article.
Funding The Competitive Research Funding of the Tampere University Hospital (Grants 9M124 and 9M128) and the Orion-Farmos Research Foundation Financing have supported the present study by funding the salary for VR during the preparation of the manuscript.
Competing interests VR has received honoraria from Abbvie, BMS, Pfizer, Roche and UCB Pharma. HK has received honoraria from Abbvie, Pfizer and Schering-Plough. MK has received honoraria and consulting fees from Abbvie, BMS, GSK, MSD, Pfizer, Roche and UCB Pharma. KP has received honoraria and consulting fees from Abbvie, BMS, MSD Finland, Pfizer and UCB Pharma. PH has received honoraria and consulting fees from Abbott, Astra-Zeneca, BMS, GSK, MSD Finland, Mundipharma, Pfizer, Roche and UCB Pharma. ML-R has received honoraria and consulting fees from Abbott, BMS, GSK, MSD, Pfizer, Roche, Schering-Plough and UCB Pharma. TM has received honoraria and consulting fees from Abbott, Amgen, Astra, BMS, Ely Lilly, GSK, MSD, Pfizer, Schering-Plough, Servier, Roche and UCB Pharma. HB and KI have nothing to disclose.
Ethics approval The ethics committees of all participating hospitals approved the study.
Provenance and peer review Not commissioned; externally peer reviewed.