Adding baseline protein biomarkers to clinical predictors does not enhance prediction of treatment response to a methotrexate strategy in early rheumatoid arthritis

Recently, we identified baseline higher disease activity score assessing 28 joints, current smoking and no alcohol consumption as predictors of inadequate response (IR) to methotrexate (MTX), used with or without other conventional synthetic disease modifying anti-rheumatic drugs, here designated as ‘MTX+’, in new-onset rheumatoid arthritis (RA).1 For those with a predicted IR to ‘MTX+’, a more intensive treatment strategy could be initiated, if prediction would be reliable. Therefore, we investigated, within the same patient population, protein biomarkers for additive predictive value to these clinical predictors. A model was developed using data from patients with RA in the U-Act-Early trial (ClinicalTrials.gov number NCT01034137) treated with a step-up MTX strategy (n=106) and was validated in patients who received MTX therapy (n=80) in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH, ISRCTN26791028).2,3 IR to ‘MTX+’ therapy was defined as the need to initiate a biological within the first treatment year. In baseline serum, 85 proteins were analysed in 2014 using multiplex Luminex profiling; seven candidate proteins, identified by partial least square discriminant analyses, were remeasured in 2018. Clinical baseline characteristics of the patients in both studies are shown in table 1. Of the proteins identified in the development cohort, in the …