Tocilizumab

Humanized monoclonal antibody directed against the receptor of the cytokine IL-6, tocilizumab was developed for the treatment of rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis (Still syndrome). There is evidence that tocilizumab is helpful in progressive scleroderma.

Tocilizumab binds to soluble as well as cell membrane-bound IL-6 receptors and to IL-6 receptors. This prevents the binding of IL-6 to its specific receptor. As a result, inflammatory signals are suppressed by interrupting the IL-6 signalling pathway. In various pretreated patients with RA, tocilizumab was effective as monotherapy or in combination with methotrexate (MTX) and other DMARDs: About 30% of patients in the Phase III studies achieved remission within 24 weeks, i.e. an almost complete reduction of disease symptoms.

Moderate to severe, active rheumatoid arthritis that has not responded adequately to previous treatment with one or more antirheumatic drugs ( DMARDs) or TNF-alpha inhibitors Tocilizumab can be administered as a combination therapy with MTX or as a monotherapy (e.g. for MTX intolerance). Also approved for giant cell arteritis (RZA) in combination with MTX or as monotherapy.

A smaller study exists for systemic lupus erythematosus. A significant improvement in the disease activity of SLE was found in 8 out of 15 patients. Arthritis improved in 7 patients, and the concentration of DNA-AK was reduced, as were IgG levels.

There are single case reports of positive effects in systemic scleroderma (Khanna D et al. 2018).

There is insufficient data on the use of tocilizumab in pregnant women. Therefore, the potential risk to humans is not known.

The recommended dosage in RA is 8 mg/kg body weight per infusion every four weeks. Dosages above 800 mg per infusion are not recommended for persons over 100 kg body weight. Doses greater than 1.2 g have not been investigated in clinical trials. The infusion duration is about one hour.

For treatment of systemic juvenile idiopathic arthritis, tocilizumab at a dose of 8 mg/kg body weight every two weeks in children ≥ 30 kg or at a dose of 12 mg/kg body weight in children under 30 kg.

The following adverse drug reactions (ADRs) may occur during treatment with tocilizumab: respiratory or herpes infections, other serious infectious diseases, gastritis, stomatitis, exanthema, arterial hypertension, liver elevation, leukopenia, neutropenia. A female patient with rheumatoid arthritis treated with tocilizumab was reported to have fatal anaphylaxis.

There are indications of a possible connection between the administration of tocilizumab and the occurrence of psoriasis or the worsening of existing psoriasis.

Blockade IL-6 activity inhibits the synthesis of acute phase proteins (e.g. CRP) by the liver. This eliminates the diagnostically important increase in CRP in the early phase of infection. This can lead to erroneous clinical evaluations (BSG control)

1. Benedetti F et al (2010) Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis: Efficacy Data From the Placebo-Controlled 12-Week Part of the Phase 3 TENDER Tria . Ann Rheum Dis 2010; 69 (Suppl 3): 146 Arthritis Rheum. 2010 Feb;62(2):542-52.
2. Gabor G et al (2012) Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis and Rheumatism 62: 542 - 552
3. Khanna D et al (2018) Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: resultsfrom
   the open-label period of a phase II randomised controlled trial
   (faSScinate). Ann Rheum Dis 77:212-220.
4. Shima Y et al (2010) The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab. Rheumatology 49: 2408-2412