Sarilumab

Source: UK SPC (eMC) for Kevzara 150 mg solution for injection in pre-filled pen, §4.2 (https://www.medicines.org.uk/emc/product/15435/smpc). The same 200 mg once every 2 weeks dose applies to both licensed indications. PRESENTATION NOTE: the fetched SPC document is titled 'Kevzara 150 mg solution for injection in pre-filled pen' while the recommended dose in its own §4.2 is 200 mg every 2 weeks, and §4.2 refers to administering 'the total content (1.14 ml) of the pre-filled pen' - sarilumab is supplied in both 150 mg/1.14 ml and 200 mg/1.14 ml presentations (per the US label §3), so the strength of the device must match the intended dose. Confirm the presentation before publishing. RHEUMATOID ARTHRITIS: recommended dose 200 mg once every 2 weeks subcutaneously. POLYMYALGIA RHEUMATICA: recommended dose 200 mg once every 2 weeks subcutaneously, in combination with a tapering course of systemic corticosteroids, after which sarilumab can be continued as monotherapy; data are available in patients treated for up to 1 year, so treatment beyond 52 weeks should be guided by disease activity, physician discretion and patient choice. TREATMENT INITIATION: initiating treatment is not recommended in patients with a low neutrophil count (absolute neutrophil count less than 2 x 10^9/L) or a platelet count below 150 x 10^3/microlitre. Treatment must be withheld in patients who develop a serious infection until the infection is controlled. DOSE MODIFICATION IN RHEUMATOID ARTHRITIS: reduction of dose from 200 mg once every 2 weeks to 150 mg once every 2 weeks is recommended for management of neutropenia, thrombocytopenia and liver enzyme elevations. ANC greater than 1 x 10^9/L - maintain current dose; ANC 0.5-1 x 10^9/L - withhold until greater than 1 x 10^9/L, then resume at 150 mg every 2 weeks and increase to 200 mg every 2 weeks as clinically appropriate; ANC less than 0.5 x 10^9/L - discontinue. Platelets 50 to 100 x 10^3/microlitre - withhold until greater than 100 x 10^3/microlitre, then resume at 150 mg every 2 weeks and increase to 200 mg as clinically appropriate; platelets less than 50 x 10^3/microlitre - if confirmed by repeat testing, discontinue. ALT greater than 1 to 3 x ULN - consider clinically appropriate dose modification of concomitant DMARDs or immunomodulatory agents; ALT greater than 3 to 5 x ULN - withhold until less than 3 x ULN, then resume at 150 mg every 2 weeks and increase to 200 mg as clinically appropriate; ALT greater than 5 x ULN - discontinue. DOSE MODIFICATION IN POLYMYALGIA RHEUMATICA: dosage modifications have not been studied in PMR; discontinue sarilumab in PMR patients who develop neutropenia (ANC below 1 x 10^9/L at the end of the dosing interval), thrombocytopenia (platelet count below 100 x 10^3/microlitre) or AST/ALT elevations 3 times above the ULN. MISSED DOSE: if 3 days or less since the missed dose, administer the next dose as soon as possible and give the subsequent dose at the regularly scheduled time; if 4 days or more, give the subsequent dose at the next regularly scheduled time and do not double the dose. HEPATIC IMPAIRMENT: safety and efficacy have not been studied in patients with hepatic impairment, including patients with positive hepatitis B or hepatitis C serology. ELDERLY: no dose adjustment is required in patients over 65 years of age, but caution should be used given the higher incidence of infections in the elderly. PAEDIATRIC (no per-kg dose is stated): the UK SPC states the safety and efficacy of the sarilumab pre-filled pen in children less than 18 years of age have not been established and no data are available; the pre-filled pen has not been studied in paediatric patients. For cross-reference only, the US label additionally approves polyarticular juvenile idiopathic arthritis at 200 mg subcutaneously once every 2 weeks (maximum dose 200 mg) for patients weighing 63 kg or greater using the 200 mg/1.14 mL pre-filled syringe, and is not approved below 63 kg because of the lack of an appropriate dosage form - that is a weight-threshold dose, not a per-kg dose, and it is not in the UK SPC. Verify any under-18 use against a children's formulary. PRESCRIBER: treatment should be initiated and supervised by healthcare professionals experienced in the diagnosis and treatment of the condition; patients must be given the patient card. Patients must be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating treatment.