Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis

Abstract

Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor). A network meta-analysis (NMA) included the indirect and direct evidence previously selected. In total, 207 articles were included describing 68 RCTs. The NMA showed that tocilizumab monotherapy was superior to standard care (ACR20, OR 13.27, 95 % CrI [3.958, 43.98]; ACR50, 17.45 [10.18, 31.24]; ACR70, 37.77 [7.226, 216.3]; EULAR, 10.42 [1.963, 54.8]); and methotrexate (MTX; ACR50, OR 5.44 [4.142, 7.238]; ACR70, 7.364 [1.4, 30.83]; EULAR, 4.226 [1.184, 15.58]) at 26 weeks. Similarly, the combination of tocilizumab + MTX was significantly better than standard care/placebo and MTX alone for ACR20, ACR50, ACR70, and EULAR at 26 weeks (OR 18.63 [5.32, 66.81]; 24.27 [14.5, 41.91]; 46.13 [10.08, 277]; 14.23 [2.493, 84.02]; 4.169 [2.267, 7.871]; 5.44 [4.142, 7.238]; 8.731 [4.203, 19.29]; 7.306 [4.393, 13.04], respectively). At 52 weeks, compared to MTX alone, tocilizumab + MTX was significantly better for ACR20 and ACR50 response. Few significant differences were found between tocilizumab (alone or in combination) and any other biologics. Results must be considered in context with the limitations of the available evidence. This NMA suggests that tocilizumab was superior to cDMARDs and as effective as other biologics for RA.

Baseline metabolic profiles of early rheumatoid arthritis patients achieving sustained drug-free remission after initiating treat-to-target tocilizumab, methotrexate, or the combination: insights from systems biology

“…Initiating treatment, aiming for sustained remission or low disease activity early in the course of the disease, is important to preserve physical function and improve long-term prognosis [ 5 – 7 ]. Biological disease-modifying anti-rheumatic drugs (DMARDs) are to date mainly used as the second line of therapy in the management of early RA, although several studies showed their superior efficacy over traditional DMARDs in reducing disease activity and halting joint damage [ 8 , 9 ]. Starting biological therapy in newly diagnosed RA patients as standard care, however, still remains highly controversial considering costs and unnecessary exposure to adverse events as a proportion of patients will be over-treated when using such an approach.…”

In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis

“…18 These newer therapeutic targets have complex and variable effects on T-cell activation, and current therapeutics aimed at any one of these targets have varying interactions with the inflammatory environment, highlighting the urgency to develop tools to both investigate relationships of immune-modulating networks in vivo and monitor the immune-based effects of therapy in patients. 19-26 …”

Prediction of rituximab and tocilizumab efficiency in rheumatoid arthritis

“…[4]. В одном из мета-анализов [5] выявлено преимущество тоцилизумаба перед другими БЛС. Однако судить о преимуществах одного БЛС перед другими сложно ввиду ничтожно малого количества прямых «голова к голове» исследований эффективности БЛС между собой.…”

“…После связывания с ритуксимабом, В-клетки погибают вследствие запуска ряда механизмов, включающих антитело-зависимую клеточно-опосредованную цитотоксичность, комплемент-зависимую цитотоксичность и апоптоз [7]. При изучении возможных предикторов ответа на анти-В-клеточную терапию установлена хорошая эффективность ритуксимаба при серопозитивном РА, при значительном повышении АЦЦП и РФ (больше трех верхних границ норм) [5]. Положительный эффект анти-В-клеточной терапии ритуксимабом наблюдался у пациентов с васкулитом, кератитом, склеритом, легочными узелками и синдромом Фелти [8][9][10].…”