Burden of dose escalation with tumour necrosis factor inhibitors in rheumatoid arthritis: a systematic review of frequency and costs.

OBJECTIVES: Optimising therapy to minimise disease activity is the goal for treating rheumatoid arthritis (RA) today. In refractory disease requiring biologics, the ability to modify therapy may be limited. In the case of the most widely used biologics, the TNF inhibitors (TNFi), dose escalation consisting of increasing the dose and/or shortening the interval between doses is often reported. METHODS: We systematically searched PubMed, EMBASE, Cochrane and Centre of Disseminated Reviews for reports of dose escalation of TNFi in RA and the economic effects of such a practice. RESULTS: Of 41 publications, 36 reported dose escalation and a weighted proportion of dose escalators was calculated for each drug. The proportion of dose escalators varied widely (adalimumab 7.5% to 36%, etanercept 0% to 22%, and infliximab 0% to 80%) due to a variety of methods for defining dose escalation. Based on 33 studies, the weighted proportion of dose escalators was adalimumab 14.9%, etanercept 4.9% and infliximab 41.7%. Six studies reported economic data comparing dose escalators with non-dose escalators. Adalimumab drug costs increased 27% to 43%, with total costs increasing 28% to 34%; infliximab drug costs increased 14% to 71%, RA-related costs increased 25% to 54% and total costs increased 14% to 34% and etanercept drug costs increased 3.2% to 19%, RA-related costs increased 4.5% and total costs increased 2.2% to 15%. CONCLUSIONS: Escalating the dose of TNFi in inadequate responders in RA is widespread, occurring most frequently with infliximab and least with etanercept. This practice not only increases drug costs, but also RA-related and total costs.