Table 1 Biologicals frequently used in JIA
Generic name | Brand name | Target | Origin/isotype | Registered indication for JIA | Route | Half-life | Contraindication | Very common side effects (in >10% of patients) | Expected time of response | Average cost first year, excluding VATa |
|---|---|---|---|---|---|---|---|---|---|---|
Abatacept | Orencia® | Inhibition of T-cell CD28-costimulation by binding CD80/ CD86 on APC | Human CTLA4 fused to FC domain of IgG1 | Yes (age >6 years) | IV | 13.1 days | Serious and uncontrollable infections | Headache | <4 months | €9,412 (monthly) |
Adalimumab | Humira® | Specific binding to TNF and blocking the interaction of TNF with p55 and p75 membrane-bound TNF receptors | Human monoclonal anti-TNF-α antibody of IgG1-isotype | Yes (age ≥4 years) | SC | 2 weeks | Sepsis and serious infections. Active tuberculosis. Moderate- severe heart failure (NYHA class III to IV) | Respiratory tract infections, leukopenia (neutropenia), anemia, elevated lipids and liver enzymes, headache, myalgia, abdominal pain, nausea, vomiting, skin rash, injection site reaction | <3 months | €14,125 (every 2 weeks) |
Anakinra | Kineret® | Competitive inhibition of IL-1α and -1β by binding to IL-1 type I receptor | A recombinant, non-glycosylated form of the naturally occurring human IL-1 receptor antagonist | No, but already standard of care | SC | 4 to 6 hours | Hypersensitive to proteins produced by Escherichia coli. Serious renal failure (creatinine- clearance <30 ml/ minute) | Injection site reaction, headache | <1 week | €13,818 (daily) |
Canakinumab | Ilaris® | Specific binding to human IL-1β | Human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype | No, u.i. for SJIA | SC | 23 to 26 days | Active serious infection. | Injection site reaction, (transient) vertigo, nasopharyngitis | <1 week | €132,000 (monthly) |
Certolizumab | Cimzia® | Specific binding to TNF-α | Humanized (from mouse) Fab' fragment against TNF-α conjugated with polyethylene glycol. Lacks Fc portion | No, u.i. for poly-JIA | SC | 14 days | Active tuberculosis or other serious infections. Moderate-severe heart failure (NYHA class III to IV) | None | <3 months | €16,076 (monthly) |
Etanercept | Enbrel® | Specific binding to TNF-α and lymphotoxin | Human TNF receptor 2 fused with the Fc portion of IgG1 | Yes (age ≥ 2 years) | SC | 70 hours | Sepsis and active infections | Infections (especially upper respiratory tract, cystitis and skin), mostly mild injection site reaction | <3 months | €7,065 (weekly) |
Golimumab | Simponi® | Specific binding to TNF-α | Human monoclonal anti-TNF-α antibody of IgG1-isotype | No, u.i. for poly-JIA | SC | 12 days | Active tuberculosis or other serious infections. Moderate-severe heart failure (NYHA class III to IV) | Upper respiratory tract infections | 14 weeks | €14,125 (monthly) |
Infliximab | Remicade® | Specific binding to TNF-α | Chimeric (human- mouse) IgG1 monoclonal antibody against TNF-α | No | IV | 8 to 9.5 days | Active tuberculosis or other serious infections. Moderate-severe heart failure (NYHA class III to IV). Hypersensitive for murine proteins | None | <3 months | €5,225 (every 8 weeks) |
Rituximab | MabThera® | Specific binding to B-cell CD20-antigen resulting in apoptosis of B cells | Chimeric human-mouse monoclonal antibody, glycosylated immunoglobulin with human IgG1 Fc domain and Mouse Fab domain | No | IV | Highly variable: 6 to 62 days | Hypersensitive for murine proteins. Active serious infections. Severe heart failure (NYHA class IV) | Infusion-related reactions, infections of upper respiratory and urinary tract, headache | <3 months | €3,284 (for three treatments) |
Tocilizumab | RoActemra® | Inhibits IL-6 signaling by specific binding to human IL-6 receptor | Humanized (from mouse) IL-6 monoclonal antibody of IgG1-isotype | Yes for SJIA (age ≥ 2 years), u.i. for poly-JIA | IV | 23 days for SJIA | Active serious infections | Upper respiratory tract infections, hypercholesterolemia | <10 weeks | €15,200 (every 2 weeks) |