Critical appraisal of tocilizumab in the treatment of moderate to severe rheumatoid arthritis

Figures & data

Table 1 Summary of efficacy and safety results from phase III trials of tocilizumab

Trial	N	Treatment arms	Main efficacy results	Other efficacy results	Safety outcomes	Duration
LITHE^Citation30	1196	8 mg/kg tocilizumab, 4 mg/kg tocilizumab, or placebo once every 4 weeks	Tocilizumab significantly inhibited progression of joint damage	With 8 mg/kg tocilizumab: ACR20: 56%,ACR50: 36% ACR70: 20%	No differences in AEs among treatment arms	2 years
SAMURAI^Citation31	306	8 mg/kg tocilizumab once every 4 weeks or DMARDs	Patients taking tocilizumab had significantly less radiographic disease progression than patients treated with DMARDs	Proportion of patients achieving an ACR20, ACR50, and ACR70 response was statistically superior to the DMARD group and signs and symptoms were more improved in patients receiving tocilizumab	Similar proportions of mild to moderate AEs (89% vs 82%) and serious AEs (18% vs 13%) for tocilizumab and DMARDs, respectively	52 weeks
SATORI^Citation32	125	8 mg/kg tocilizumab every 4 weeks plus MTX placebo (tocilizumab group) or tocilizumab placebo plus MTX 8 mg/week (control group)	25.0% and 80.3% of patients in the control and tocilizumabs groups achieved ACR20, respectively	Tocilizumab significantly decreased serum VEGF levels	Incidences of AEs were 72% and 92% (serious AEs: 4.7 and 6.6%; serious infections: 1.6 and 3.3%) in control and tocilizumab groups, respectively; all serious AEs improved with adequate treatment	24 weeks
OPTION^Citation33	623	8 mg/kg tocilizumab, 4 mg/kg tocilizumab, or placebo every 4 weeks with MTX	More ACR20 responses in tocilizumab groups than in placebo group (odds ratio 4.0 [95% CI 2.6–6.1], P < 0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7–3.9], P < 0 0001 for 4 mg/kg vs placebo)	Patients taking tocilizumab had greater improvements in HAQ-DI scoring of physical function from baseline, FACIT-Fatigue scores, and physical and mental SF36 scores than those given a placebo	More people in the tocilizumab group had at least 1 AE with the most common serious AEs being serious infections or infestations 6 patients in 8 mg/kg group, 3 in the 4 mg/kg group, and 2 in the placebo group	24 weeks
RADIATE^Citation34	499	8 mg/kg tocilizumab, 4 mg/kg tocilizumab, or placebo every 4 weeks with MTX	ACR20 was achieved in 50% of the tocilizumab 8 mg/kg group, as compared to 30% in the 4 mg/kg group and 10% in the placebo group	Greater improvements in HAQ values from baseline achieved by 8 mg/kg tocilizumab (P < 0.001) and 4 mg/kg tocilizumab (P = 0.003) relative to placebo; DAS28 and EULAR responses also were greater in tocilizumab groups	Mild and moderate cases of infection, gastrointestinal upset, rash, and headaches were frequently reported in both the tocilizumab-treated and placebo-control group	24 weeks
TOWARD^Citation35	1220	8 mg/kg tocilizumab or placebo every 4 weeks	Significantly more ACR20 responses achieved in the tocilizumab plus DMARD group than in the control group (61% vs 25%; P < 0.0001)	Tocilizumab was superior to placebo in DAS28 and EULAR responses	AEs reported in 73% of the tocilizumab-treated patients and 61% of the placebo-treated patients; majority of serious AEs occurred in the tocilizumab group	24 weeks
AMBITION^Citation36	673	Tocilizumab 8 mg/kg monotherapy vs escalating doses of MTX	ACR20 response, was statistically superior in those who received tocilizumab monotherapy (70%) compared to those in the methotrexate group (52.5%)	DAS28 < 2.6 achieved by significantly more patients taking tocilizumab than MTX (34% vs 12%)	No differences in the incidence of AEs between tocilizumab and placebo groups; most common AE was infection	24 weeks

Abbreviations: MTX, methotrexate; AEs, adverse events; DMARDs, disease-modifying antirheumatic drugs; HAQ, Health Assessment Questionnaire; DAS28, Disease Activity Scale in 28 Joints; EULAR, European League Against Rheumatism Responses; VEGF, vascular endothelial growth factor.

Table 2 Adverse events and number of occurrences in published clinical trials of tocilizumab in rheumatoid arthritis

	Nishimoto^Citation37	Smolen^Citation45 CHARISMA	Nishimoto^Citation31 SAMURAI		Smolen^Citation33 OPTION
			Tocilizumab 8 mg/kg	Conventional DMARDS	Tocilizumab 4 mg/kg	Tocilizumab 8 mg/kg	Placebo
Total number of patients	109	359	157	145	212	206	129
Nasopharyngitis		23	56	47	11	12	10
Rash		24	17	6	13	11	3
Fever	6	3
Headache	5	29	11	3	15	14	9
Increased blood pressure	3	15			7	8	9
Infusion reaction	16		11
Pruritis	5		9	2
Sleepiness	3
Stomatitis	7	9	9	13
Upper respiratory infection	14	29			12	17	13
Cough		10			7	3	3
Dyspnea		6			3	3	0
Fatigue		9			3	6	5
Pharyngeal pain		6			2	4	3
Eczema			9	6
Nausea			9	2
Paronychia			9	1
Vertebral compression fracture			3	3
Any gastrointestinal disordera		37	21	18	63	68	55
Mouth ulcers					4	5	1
Peptic ulcers					1	0	2
Peripheral edema					5	4	2
Pyrexia					2	1	5

a Any gastrointestinal disorder includes abdominal discomfort, dyspepsia, vomiting, and diarrhea.

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