Background When initiating therapy with disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), treatment adoptions are recommended if no improvement in disease activity is seen within 3 months, or if the treatment target has not been reached by 6 months.1 A pooled analyses from several pivotal RCTs showed that RA patients who did not achieve a minor treatment response by 3 months were unlikely to reach the treatment target by 6 months.2
Objectives To examine what level of treatment response is needed after 3 months of therapy in order to achieve the treatment target of remission (REM) or low disease activity (LDA) by 6 months in a routine clinical setting.
Methods Data were provided by NOR-DMARD, a prospective, multicentre, observational study. We selected RA-patients enrolled between December 2000 and November 2012, who were biological DMARD-naïve and had a moderate or high disease activity (MDA or HDA, respectively) according to the Simplified Disease Activity Index (SDAI) when initiating therapy. All analyses were performed for the total group of included patients (n=1610), as well as for the following sub-groups: disease duration over (n=895) or under (n=681) 12 months, baseline SDAI MDA (n=825) or HDA (n=785), DMARD-naive patients starting methotrexate (MTX) (n=537) and patients starting tumour necrosis factor inhibitor (TNFi) (n=248). We used a diagnostic test approach, created receiver operating characteristic curves and generated sensitivities, specificities and likelihood ratios (LRs) for all improvement cut-points (0–100%) at the 3-month visit. Furthermore, we tested the ability of established response criteria (SDAI 50/70/85 response) at 3 months to predict the desired target of SDAI remission or SDAI LDA at 6 months.
Results At inclusion median (IQR) disease duration was 2 (0.2–8.8) years and mean (SD) SDAI was 28.3 (12.8). At 6 months 46.8% of all patients had achieved LDA and 10.8% had reached remission. Not achieving a minor treatment response (SDAI 50% response) by 3 months was associated with decreased probability of reaching remission at 6 months (LR- 0.27), but gave little prognostic information regarding the probability of reaching LDA (LR- 0.49). Patients with HDA at baseline who did not achieve at least 50% improvement in disease activity by 3 months had very low probability of reaching the treatment target by 6 months (LR- 0.15 for remission and LR- 0.30 for LDA). SDAI 85% response at 3 months was predictive of reaching the treatment target at 6 months (LR+ 6.56 for remission and LR+ of 6.45 for LDA). For the total group of patients, a reduction in SDAI of 60.2% was needed at 3 months to predict LDA at 6 months with 80% specificity, while 69.2% improvement was necessary to predict remission.
Conclusions These results from a routine clinical setting confirm results from RCTs demonstrating a predictive association between treatment response at 3 months and achievement of the treatment target by 6 months in RA-patients. Assessments at 3 months can inform clinicians to continue or adjust ongoing DMARD-therapy in a treat-to-target strategy aiming for remission or LDA by 6 months.
Smolen JS, et al. Ann Rheum Dis 2014;73(3):492–509.
Aletaha D, et al. Ann Rheum Dis 2016;75(8):1479–85.
Disclosure of Interest V. Norvang: None declared, I. Olsen: None declared, E. Kristianslund: None declared, T. Uhlig: None declared, T. Kvien Consultant for: AbbVie, Biogen, BMS, Boehringer, Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Norvartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, UCB, D. Aletaha Consultant for: Abbvie, BMS, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, UCB, Speakers bureau: Abbvie, BMS, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, UCB, J. Smolen Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, UCB, E. Haavardsholm Grant/research support from: AbbVie, Pfizer, Roche, MSD, UCB, Consultant for: AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB