Short-term suboptimal response criteria for predicting long-term non-response to first-line disease modifying therapies in multiple sclerosis: A systematic review and meta-analysis

INTRODUCTION There is no consensus about short-term suboptimal response to first-line treatments in relapsing-remitting multiple sclerosis. METHODS We searched studies with interferon beta or glatiramer acetate in which a long-term (≥ 2 years (y)) outcome could be predicted using short-term (≤ 1 y) suboptimal response criteria (EDSS-, imaging- and/or relapse-based). We obtained pooled diagnostic accuracy parameters for the 1-y criteria used to predict disability progression between 2-5 y. RESULTS We selected 45 articles. Eight studies allowed calculating pooled estimates of 16 criteria. The three criteria with best accuracy were: new or enlarging T2-weighted lesions (newT2) ≥ 1 (pooled sensitivity: 85.5%; specificity:70.2%; positive predictive value:48.0%; negative predictive value:93.8%), newT2 ≥ 2 (62.4%, 83.6%, 55.0% and 87.3%, respectively) and RIO score ≥ 2 (55.8%, 84.4%, 47.8% and 88.2%). Pooled percentages of suboptimal responders were 43.3%, 27.6% and 23.7%, respectively. Pooled diagnostic odds ratios were 14.6 (95% confidence interval: 1.4-155), 9.2 (1.4-59.0) and 8.2 (3.5-19.2). CONCLUSIONS All criteria had a limited predictive value. RIO score ≥ 2 at 1-y combined fair accuracy and consistency, limiting the probability of disability progression in the next years to 1 in 8 optimal responders. NewT2 ≥ 1 at 1-y had similar positive predictive value, but diminished the false negatives to 1 in 16 patients. More sensitive measures of treatment failure at short term are needed.