Interleukin-6 inhibitors in the treatment of rheumatoid arthritis

Figures & data

Table 1 Clinical trials of tocilizumab in rheumatoid arthritis

Trial	Trial design	Number of patients	Average number of DMARDs failed	Protocol	Results
Nishimoto et al 2004, 2007a	DBRPCT	162	5	Tocilizumab 4 or 8 mg/kg iv or placebo q4weeks	At 3 months: ACR20: 8 mg/kg MRA – 78%, 4 mg/kg MRA – 57%, placebo – 11%. ACR50: 8 mg/kg MRA – 40%, placebo – 1.9%. At 5 years: ACR20: 8 mg/kg MRA – 84.2% ACR50: 8 mg/kg MRA – 68.4% ACR70: 8 mg/kg MRA – 44.7%
Maini et al 2006 CHARISMA	Phase II DBRPCT	359	2	Tocilizumab 2, 4, or 8 mg/kg monotherapy, or + MTX, or MTX + placebo	At week 16: ACR20: 2 mg/kg MRA – 31%, 4 mg/kg MRA – 61%, 8 mg/kg MRA – 63%, MTX – 41%, 2 mg/kg MRA + MTX – 64%, 4 mg/kg MRA + MTX – 63%, 8 mg/kg MRA + MTX + placebo – 74%. ACR50: 2 mg/kg MRA + MTX – 32%, 4 mg/kg MRA + MTX 37%, 8 mg/kg MRA + MTX 53%, MTX + placebo – 29%. ACR70: 8 mg/kg MRA + MTX 37%, MTX + placebo – 16%.
Smolen et al 2008 OPTION	Phase III DBRPCT	623	MTX	Tocilizumab 4 or 8 mg/kg iv q4weeks + MTX or placebo + MTX	At week 24: ACR20: 4 mg/kg MRA + MTX – 47.9%, 8 mg/kg MRA + MTX – 58.5%, MTX + placebo – 26.5% ACR50: 8mg/kg MRA + MTX – 43.9%, MTX + placebo – 10.8% ACR70: 8 mg/kg MRA + MTX – 22.0%, MTX + placebo – 2.0%. EULAR good/moderate response: 8 mg/kg MRA + MTX – 79.5%, 4 mg/kg MRA + MTX – 61.9%, MTX + placebo – 34.8%. Mean ▵ HAQ: 8 mg/kg MRA + MTX – –0.55, 4 mg/kg MRA + MTX – –0.52, MTX + placebo – –0.34 ▵ SF-36 PCS: 8 mg/kg MRA + MTX – 9.5, 4 mg/kg MRA + MTX – 9.7, MTX + placebo – 5.0 ▵ SF-36 MCS: 8 mg/kg MRA + MTX – 7.3, 4 mg/kg MRA + MTX – 5.7, MTX + placebo – 2.7 ▵ FACIT-Fatigue: 8 mg/kg MRA + MTX – 8.6, 4 mg/kg MRA + MTX – 7.29, MTX + placebo – 4.0.
Genovese et al 2007; Gomez-Reino et al 2007TOWARD	Phase III DBRPCT	1216	≥1	Tocilizumab 8 mg/kg + DMARD or DMARD + placebo	At week 24: ACR20: 8 mg/kg MRA + DMARD – 60.8%, DMARD + placebo – 24.5% ACR50: 8 mg/kg MRA + DMARD – 37.6%, DMARD + placebo – 9.0% ACR70: 8 mg/kg MRA + DMARD – 20.5%, DMARD + placebo – 2.9%. Mean ▵ HAQ: 8 mg/kg MRA + DMARD – –0.47, DMARD + placebo – –0.20 ▵ SF-36 PCS: 8 mg/kg MRA + DMARD – 8.9, DMARD + placebo – 4.1 ▵ SF-36 MCS: 8 mg/kg MRA + DMARD – 5.3, DMARD + placebo – 2.3.
Nishimoto et al 2007b SAMURAI	Phase III DBRPCT	320	2	Tocilizumab 8 mg/kg iv q4weeks or DMARDs	At week 52: ACR20: 8 mg/kg MRA – 78%, DMARDs – 34% ACR50: 8 mg/kg MRA – 64%, DMARDs – 13% ACR70: 8 mg/kg MRA – 44%, DMARDs – 6%. Mean ▵ TSS: 8 mg/kg MRA – 2.3, DMARDs – 6.1.

Abbreviations: MRA, tocilizumab; DBRPCT, double-blind randomized placebo-controlled trial; ACR, American College of Rheumatology; DMARD, disease-modifying anti-rheumatic drug; MTX, methotrexate; ▵, change; TSS, mean total modified Sharp score; EULAR, European United League Against Rheumatism; SF-36, Short Form 36 Health Survey; PCS, physical component score; MCS, mental component score; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue score.

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NishimotoNMiyasakaNYamamotoK2007aLong-term safety and Efficacy of tocilizumab (an anti-IL-6 receptor monoclonal antibody) in monotherapy in patients with rheumatoid arthritisAnn Rheum Dis66Suppl IIOP0227

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MainiRNTaylorPCSzechinskiJ2006Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexateArthritis Rheum5428172916947782

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SmolenJBeaulieuARubbert-RothA2008Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trialLancet37196179879718358926

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GenoveseMMcKayJNasonovE2007IL-6 receptor inhibition with Tocilizumab reduces disease activity in patients with rheumatoid arthritis with inadequate response to a range of DMARDs: The TOWARD studyACR/ARHP Scientific Meeting 2007Presentation L15.

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Gomez-ReinoJJFairfaxMJPavelkaK2007Targeted inhibition of IL-6 signaling with tocilizumab improves quality of life and function in patients with rheumatoid arthritis with inadequate response to a range of DMARDsACR/ARHP Scientific Meeting 2007Poster 522.

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NishimotoNHashimotoJMiyasakaN2007bStudy of active controlled monotherapy used for rheumatoid arthritis, and IL-6 inhibitor (SAMURAI): -Evidence of clinical and radiographic benefit from an x-ray reader-blinded randomized controlled trial of tocilizumabAnn Rheum Dis661162717485422

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