Tocilizumab: from the rheumatology practice to the fight against COVID-19, a virus infection with multiple faces

Figures & data

Figure 1. Pleiotropic effects of interleukin-6 (IL-6).

Table 1. Current indications of tocilizumab.

Autoimmune/ inflammatory condition	U.S. Food and Drug Administration (FDA)	FDA administration route	European Medicines Agency (EMA)	EMA administration route
RA	Adults with active RA and inadequate response to DMARDs	IV or SC	Adults with severe RA and inadequate response to methotrexate, or with moderate to severe active RA not responding to DMARDs or TNF blockers	IV or SC
Systemic JIA	Patients ≥ 2 years with active disease	IV	Patients ≥ 1 year with poor response to NSAIDs and GC	IV
Polyarticular JIA	Patients ≥ 2 years with active disease	IV	Patients ≥ 2 years with active disease, not responding to methotrexate	IV or SC
GCA	Adult patients	SC	Adult patients	SC
CRS due to CAR-T cell therapy	Adults and pediatric patients ≥2 years with CAR T cell-induced severe or life-threatening CRS	IV	Adults and pediatric patients ≥2 years with CAR T cell-induced severe or life-threatening CRS	IV

Abbreviations: CAR = Chimeric antigen receptor; CRS = Cytokine release syndrome; DMARDs = Disease modifying anti-rheumatic drugs; GC = Glucocorticoids; GCA = Giant cell arteritis; IV = Intravenous; JIA = Juvenile idiopathic arthritis; NSAIDs = Non-steroidal anti-inflammatory drugs; RA = Rheumatoid arthritis; SC = Subcutaneous; TNF = Tumor necrosis factor.

Figure 2A. Treatment protocol for COVID-19 – Part I.

(1) Remdesivir (from Gilead Sciences): loading dose of 200 mg i. v. on day 1, then 100 mg i.v. for the following 9 days. Only antiviral likely active, trials currently ongoing.(2) Hydroxychloroquine (DOLQUINE®): 200 mg per tablet; 2 tablets (400 mg)/12 hours the first 24 hours, and subsequently, 1 tablet (200 mg)/12 hours; duration of treatment 7–14 days.(3) Colchicine (COLCHICINA SEID®): 0.5 mg per tablet; 1 tablet (0.5 mg)/12 h for 3 days, followed by 0.5 mg/day during a total of 7 days.(4) Methylprednisolone (URBASON®): 250 mg i.v./day x 3 days.(5) Tocilizumab (RoACTEMRA®): if possible, an i.v. dose of 8 mg/Kg. However, due to a shortage of stock, a dose per patient was authorized, of 600 mg (if weight ≥75 Kg) or 400 mg (if weight <75 Kg).* Additional dose of tocilizumab if available or a similar anti-IL6 agent (e.g. sarilumab, siltuximab) or anakinra (according to doses in Part II – Figure 2B).** Specified in the following section (ICU)

Figure 2B. Treatment protocol for COVID-19 – Part II.Adapted with permission from the updated protocol proposed on 20 April 2020, by Dr. Mayo at Hospital Galdakao, Bizkaia, Spain (anticoagulation recommendations not included).