Table 2 Summary of changes in lipids and lipoproteins with IL-6-blocking treatment (treatment duration <6 months)
First authorType of studyTreatment/durationChanges in lipid parameters and inflammation markersComments
Nishimoto45Multicentre, double-blind, placebo-controlled studyJapan4 mg/kg or 8 mg/kg tocilizumab every 4 weeks/12 weeks (n = 109 patients with RA)TC (mg/dl): ↑† with both doses tocilizumab; at 4 mg/kg, 185,*§; Δ14.1%;§ at 8 mg/kg, 185,*§ Δ28.6%§ (mean values) HDL (mg/dl): ↑† with both doses tocilizumab; at 4 mg/kg, 57,*§ Δ17.5%;§ at 8 mg/kg, 58,*§ Δ24.1%§ (mean values) TG (mg/dl): ↑† with both doses tocilizumab; at 4 mg/kg, 86,*§ Δ22.1%;§ at 8 mg/kg, 89,*§ Δ34.8%§ (mean values) CRP (mg/dl): ↓† with both doses tocilizumab; at 4 mg/kg, 5.1,*§ Δ–51.0%;§ at 8 mg/kg, 4.9,*§ Δ–79.6%§ (mean values) ESR (mm/h): ↓† with both doses tocilizumab; at 4 mg/kg, 71,*§ Δ–38.0%;§ at 8 mg/kg, 71,*§ Δ–71.8%§ (mean values)All patients had demonstrated an inadequate response with at least one DMARD or immunosuppressant. Patients taking prednisolone (maximum of 10 mg/day) and/or NSAIDs were permitted to continue these treatments during the study if doses had not changed during the 4-week period prior to study start.
Maini46Multicentre, double-blind, placebo-controlled, randomised studyEurope2 mg/kg, 4 mg/kg or 8 mg/kg tocilizumab every 4 weeks either as monotherapy or in combination with oral MTX once weekly, or a control of MTX once weekly plus placebo for 16 weeks (efficacy)/20 weeks (safety) (n = 359 patients with RA)TC: ↑ with tocilizumab‡ HDL: ↑ with tocilizumab‡ TG: ↑ with tocilizumab‡ TC/HDL: ↓† with 8 mg/kg tocilizumab; ↔† with 2 mg/kg or 4 mg/kg tocilizumab CRP: ↓‡ with 8 mg/kg tocilizumab; ↔‡ with 2 mg/kg or 4 mg/kg tocilizumab ESR: ↓‡ with 4 mg/kg or 8 mg/kg tocilizumab; ↔ with 2 mg/kg tocilizumabPatients had active RA, had experienced an inadequate response to MTX, and had been taking a stable dose of MTX for at least 4 weeks prior to study start. Patients were excluded from study if they demonstrated leucopenia and/or thrombocytopenia, any hepatic dysfunction or if they received DMARDs (except MTX) within 4 weeks prior to study start, or anti-TNF agents within 12 weeks of starting study medication, or leflunomide within 6 months of starting study medication.
Smolen48Multicentre, double-blind, controlled, randomised, Phase III studyInternational4 mg/kg or 8 mg/kg tocilizumab every 4 weeks or placebo with MTX at stable pre-study doses (10–25 mg/week)/24 weeks (n = 622 patients with RA)With both doses tocilizumab TC (mmol/l): ↑;† at 8 mg/kg: 5.11,* Δ0.9‡; at 4 mg/kg: 5.08,* Δ0.9‡ (mean values) HDL (mmol/l): ↑;† at 8 mg/kg: 1.47,* Δ0.1;‡ at 4 mg/kg: 1.49,* Δ0.1‡ (mean values) LDL (mmol/l): ↑;† at 8 mg/kg: 2.93,* Δ0.6;‡ at 4 mg/kg: 3.02,* Δ0.5‡ (mean values) TC/HDL: ↔ or ↓ in 92% patients with 4 mg/kg tocilizumab† ↔ or ↓ in 83.1% patients with 8 mg/kg tocilizumab† CRP (mg/dl): ↓† at 8 mg/kg tocilizumab; 2.6* with 4 mg/kg tocilizumab; 2.8* ESR: pattern similar to CRP changesPatients had moderate-to-severe active RA for >6 months with an inadequate response to MTX. Prior to study start, all other DMARDs were discontinued. If dose stable for ⩾6 weeks prior to study start, oral glucocorticoids (⩽10 mg//day prednisone or equivalent) and/or NSAIDs were permitted
Nishimoto47Multicentre, controlled, randomised, studyJapan8 mg tocilizumab every 4 weeks/52 weeks (n = 134 patients with RA)TC: anomalously ↑ in 38% of patients HDL: ↑ to above normal levels in 24% of patients LDL: anomalously ↑ in 26% of patients TG: anomalously ↑ in 17% of patients TC/HDL: ↔†Patients had active RA with disease duration of ⩾6 months and <5 years. Prior to start of study medication, anti-TNF agents and leflunomide were not allowed within 3 months and within 4 weeks, surgical treatment or change in DMARD or immunosuppressant dose or type, or plasma exchange therapies were not allowed. Oral corticosteroids (prednisolone, ⩽10 mg per day) were permitted if the dosage had not been changed within 2 weeks of starting study medication.
  • CRP, C-reactive protein; DMARDs, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein-cholesterol; LDL, low-density lipoprotein-cholesterol; MTX, methotrexate; NSAIDs, non-steroidal anti-inflammatory drugs; RA, rheumatoid arthritis; TC, total cholesterol; TG, serum triglycerides; ↑, value increased; ↓, value decreased; ↔, value stable.

  • *Baseline value.

  • †Versus baseline.

  • ‡Change over time (study duration).

  • §Value estimated from publication figure.