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's syndrome). The antibody is already approved in the EU for the treatment of inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis and cytokine release syndrome (CRS). There is evidence that tocilizumab is helpful in progressive systemic scleroderma.

Moderate to severe, active rheumatoid arthritis that has responded inadequately to previous treatment with one or more anti-rheumatic drugs(DMARDs) or TNF-alpha inhibitors. Tocilizumab can be administered as a combination therapy with MTX or as monotherapy (e.g. in cases of MTX intolerance). Also approved for giant cell arteritis (GCA) in combination with MTX or as monotherapy.

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

There are individual 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)

^RoActemra® (EU)

The efficacy of tocilizumab in systemic juvenile idiopathic arthritis was investigated in the pivotal TENDER study. After 12 weeks, 85% of patients achieved a 30% response to therapy.

COVID-19: The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommends extending the approval of RoActemra (tocilizumab) to include COVID-19. The interleukin-6 receptor antagonist marketed by Roche i

Tocilizumab is now also to be used in COVID-19 patients who are receiving systemic corticosteroids and also require oxygen or mechanical ventilation.

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