Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis

Figures & data

Table 1 Currently approved molecular targeted strategies to control RA disease activity

	Target	Dose/administration	ACR50 response in MTX-inadequate responders at 24 weeks	Main adverse effects
Rituximab	CD-20 (B-cells)	2 × 1000 mg^−1 g IV 15 days apart, single course, repeated as soon as after 6 months if necessary	26% (SERENE),^Citation40 up to 33% in seropositive patients	Infusion reactions, hepatitis B reactivation, progressive multifocal leukoencephalopathy
Abatacept	CD80/86 on APCs (T-cell activation)	3 × 10 mg/kg IV 15 days apart, then every month 125 mg SC once weekly	40% (AIM)^Citation74	Infections
Tocilizumab	IL-6R	4–8 mg/kg IV every 4 weeks	44% (OPTION)^Citation94 monotherapy	Infusion reactions, hepatotoxicity, infections, neutropenia
Anakinra	IL-1R	100 mg SC once daily (can be reduced to every other day)	17% (Phase III trial^Citation114)	Infusion reactions

Abbreviations: RA, Rheumatoid arthritis; APCs, antigen-presenting cells; IL-6R, interleukin-6 receptor; IL-1R, interleukin-1 receptor; MTX, methotrexate; IV, intravenously; SC, subcutaneously; ACR50, 50% improvement in American College of Rheumatology response criteria; AIM, Abatacept in Inadequate responders to Methotrexate; OPTION, Tocilizumab Pivotal Trial in Methotrexate Inadequate RespONders; SERENE, Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders.

EmeryPDeodharARigbyWFEfficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)Ann Rheum Dis2010691629163520488885

 PubMed Web of Science ®Google Scholar

KremerJMGenantHKMorelandLWEffects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trialAnn Intern Med200614486587616785475

 PubMed Web of Science ®Google Scholar

SmolenJSBeaulieuARubbert-RothAEffect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomized trialLancet200837198799718358926

 PubMed Web of Science ®Google Scholar

CohenSBMorelandLWCushJJA multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexateAnn Rheum Dis2004631062106815082469

 PubMed Web of Science ®Google Scholar