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)


aThe average cost per year is calculated for a 30 kg (66 lb) patient at the 2010 purchase price (excluding VAT) for pharmacies in the Netherlands. APC, antigen presenting cell; IV, intravenous; JIA, juvenile idiopathic arthritis; NYHA, New York Heart Association; SC, subcutaneous; SJIA, systemic onset juvenile idiopathic arthritis; u.i., under investigation.

Swart et al. Arthritis Research & Therapy 2013 15:213   doi:10.1186/ar4213