Special Edition of Prescrire International

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SC tocilizumab ( roactemra °) in giant cell arteritis An alternative to methotrexate

 POSSIBLY HELPFUL  For patients with giant cell arteritis, the value of adding tocilizumab to prolonged cortico- steroid therapy with gradual dose reduction over a period of 18 months to 2 years has not been evaluated. Corticosteroid therapy alone therefore remains the standard treatment. In the rare patients who cannot tolerate cortico­ steroids, tocilizumab has not been compared with methotrexate . But in one trial, adding tocilizumab to corticosteroid therapy reduced the cumulative corticosteroid dose. The adverse effect profile of tocilizumab differs from that of methotrexate , making it a use- ful option for some patients.

in France recommend tapering over 18 months to 2 years. After an average treatment duration of two years, about half of patients manage to discontinue corticosteroid therapy without relapsing (1-4). Prolonged corticosteroid treatment has many, sometimes serious adverse effects: fluid and electro- lyte disturbances, cardiovascular disorders, metabol- ic disorders (including weight gain, hyperglycaemia, and adrenal insufficiency), musculoskeletal disorders (includingmuscle atrophy and osteoporosis), skin and eye disorders; mood and behavioural disorders; immunosuppression; and infections (1,3-5). In rare patients, corticosteroid doses must be kept to a minimum, in particular those with a condition liable to be worsened by corticosteroid therapy, such as complicated diabetes, depression or severe hypertension, or those who can no longer tolerate the adverse effects of corticosteroids. Another immunosuppressant is often added in such cases, with the aim of reducing the corticosteroid dose. Methotrexate is the best-evaluated option in this situation. According to a meta-analysis of three randomised placebo-controlled trials in a total of 161 patients with newly diagnosed giant cell arter­ itis, adding methotrexate to corticosteroid therapy for 48 weeks resulted in a modest but statistically significant reduction in the frequency of relapses, and reduced the cumulative corticosteroid dose over the 48-week period by 842 mg of prednisone or equivalent compared with the placebo group, i.e. a reduction of 2.5 mg of corticosteroid per day on average (3,4,6). The main adverse effects of methotrexate are: gastrointestinal disorders (including stomatitis, ab- dominal pain and intestinal perforation); haemato- logical disorders (including agranulocytosis, anae- mia, and thrombocytopenia); liver damage; and infections (7). Tocilizumab (RoActemra°, Roche) is a monoclonal antibody that binds to interleukin 6 receptors, thus inhibiting the action of interleukin 6, a cytokine in- volved in inflammatory phenomena. Tocilizumab was already authorised in the EU for use in rheuma- toid arthritis and a few other inflammatory conditions. It has now been authorised for use by subcutaneous injection in giant cell arteritis, in combination with a tapering course of corticosteroid therapy (2,5,8). In this situation, does the addition of tocilizumab to corticosteroid therapy constitute a therapeutic advance over corticosteroid therapy alone, espe- cially for the prevention of relapses? Is tocilizumab more effective than methotrexate in the rare patients What’s new?

ROACTEMRA° - tocilizumab solution for subcutaneous injection • 162 mg of tocilizumab per pre-filled syringe or pen. ■■ immunosuppressant; anti-interleukin-6 monoclo- nal antibody ■■ New indication : “giant cell arteritis”. [EU centralised pro- cedure]

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Giant cell arteritis (also known as temporal or cra- nial arteritis, or Horton disease) is an inflammatory disease affecting the arteries, of undetermined cause. It mainly occurs in patients over the age of 70 years, predominantly women. The main symptoms are headache of varying severity, scalp tenderness (causing pain when combing or brushing hair), jaw pain on chewing, constitutional symptoms (including fever, fatigue, appetite or weight loss), inflammatory pain and joint stiffness, predominantly in the shoul- ders and hips. Signs of inflammation, including C-reactive protein (CRP) elevation, are very often present.The main complication of giant cell arteritis is sudden, irreversible blindness in one or sometimes both eyes, usually with no warning symptoms (1-3). Tapered corticosteroid therapy, sometimes adding methotrexate. Treatment of giant cell arteritis is based on high-dose oral corticosteroid therapy. Once in- flammatory markers have normalised, typically after 2 to 4 weeks of treatment, the corticosteroid dose is reduced very gradually to avoid relapses.There is no consensus over the duration of this taper. Specialists

P age 6 • P rescrire I nternational S pecial E dition 2019