Therapeutic options for patients with systemic juvenile idiopathic arthritis without macrophage activation syndrome

Drug	Dose	Therapeutic considerations
First-line therapies
Nonsteroidal antiinflammatory drug (NSAID) examples (other NSAIDs can be used)
Naproxen	5 to 10 mg/kg/dose orally twice daily (maximum 1000 mg/day)	Scheduled use at antiinflammatory doses as monotherapy for patients with mild disease. May also be as an analgesic and antipyretic for patients with moderate to severe disease who are taking immunosuppressive therapy.
Ibuprofen	10 mg/kg/dose orally 3 to 4 times daily (maximum 800 mg/dose, 2400 mg/day)
Celecoxib	Dose based on patient weight: 10 to 25 kg: 50 mg orally twice daily >25 kg: 100 mg orally twice daily or 200 mg once daily Adult dosing: 200 mg orally once to twice daily
Indomethacin	0.25 to 1 mg/kg/dose 3 to 4 times daily (maximum 50 mg/dose, 200 mg/day)
Interleukin 1 (IL-1) inhibitors
Anakinra (patients ≥8 months and ≥10 kg)	2 to 4 mg/kg SUBQ or IV once daily (maximum initial dose 100 mg/day); thereafter may escalate to a maximum of 200 mg/day partial response	An IL-1 inhibitor with or without systemic glucocorticoids is an option for the initial treatment of moderate to severe disease.
Canakinumab	4 mg/kg SUBQ once every 4 weeks (maximum dose 300 mg)
Rilonacept (patients ≥12 years)	Subcutaneous administration (dose based on patient age): Ages 12 to 17 years old: Loading dose of 4.4 mg/kg SUBQ once (maximum 320 mg); divide in 1 or 2 injections on same day at different sites if needed so each injection is ≤2 mL (160 mg) Maintenance dose of 2.2 mg/kg SUBQ once weekly (maximum dose 160 mg) beginning one week after loading dose Age ≥18 years old: Loading dose of 320 mg SUBQ given once as two separate 160 mg injections on same day at different sites Maintenance dose of 160 mg SUBQ once weekly beginning one week after the loading dose
IL-6 inhibitors
Tocilizumab	Subcutaneous administration (dose based on patient weight): <30 kg: 162 mg/dose SUBQ once every 2 weeks ≥30 kg: 162 mg/dose SUBQ once every week Intravenous administration (dose based on patient weight): <30 kg: 12 mg/kg/dose IV once every 2 weeks ≥30 kg: 8 mg/kg/dose IV once every 2 weeks (maximum 800 mg/dose)	An IL-6 inhibitor with or without systemic glucocorticoids is an option for the initial treatment of moderate to severe disease.
Adjunctive therapies for patients with certain clinical features
Intraarticular glucocorticoids
Triamcinolone acetonide or triamcinolone hexacetonide^*	0.5 to 1 mg/kg intraarticularly, up to 40 mg depending upon size of joint (range: 5 to 40 mg)	Can be used for patients with arthritis in moderate to large joints that are amenable to injection (eg, knee, wrist). Effective only for treatment of the joint that is injected. It is unusual to inject more than 3 to 4 joints at one time. Triamcinolone hexacetonide (if available) is the most effective glucocorticoid for joint injections.
Methylprednisolone acetate	1 mg/kg intraarticularly, up to 80 mg depending upon size of joint (range: 5 to 80 mg)
Systemic glucocorticoids
Prednisone, prednisolone, or methylprednisolone	Most patients: <0.5 mg/kg/day of prednisone or its equivalent (maximum dose 30 mg/day) Patients with severe disease: 1 to 2 mg/kg/day of prednisone (maximum dose 60 mg/day) or its equivalent and consideration of pulse dose glucocorticoids^¶ (ie, methylprednisolone 20 to 30 mg/kg/day [maximum dose 1 g/day])	For indications to add systemic glucocorticoids, refer to UpToDate content on the treatment of sJIA.
Second-line therapies
Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)
Methotrexate	Oral^Δ or SUBQ administration: 10 to 15 mg/m²/dose once weekly or 0.5 mg/kg/dose once weekly; (maximum 25 mg per week) Based upon initial response, may increase up to 25 to 30 mg/m² once weekly or 1 mg/kg/dose once weekly (maximum 25 mg per week) Administer with folic acid 0.4 to 1 mg orally once daily or leucovorin 2.5 to 5 mg orally once weekly on day after methotrexate dose	Can be used to treat refractory disease, especially refractory arthritis. Often combined with a bDMARD; refer to UpToDate content on the treatment of sJIA. Requires regular monitoring for the development of cytopenias and hepatotoxicity.
Leflunomide	Dose based on patient weight: <20 kg: 10 mg orally every other day 20 to 40 kg: 10 mg orally once daily >40 kg: 20 mg orally once daily	Can be used to treat refractory disease, especially refractory arthritis. Usually combined with a bDMARD; refer to UpToDate content on the treatment of sJIA. Requires regular monitoring for the development of cytopenias and hepatotoxicity.
Cyclosporine, modified	1.5 to 2.5 mg/kg orally twice daily	Can be used to treat refractory disease, especially refractory arthritis. Requires monitoring for drug levels and dose titration to target trough concentrations, as well as for development of kidney toxicity and hypertension.
Tumor necrosis factor (TNF) inhibitors
Adalimumab	Dose based on patient weight: 10 to <15 kg: 10 mg SUBQ once every 2 weeks (may escalate to weekly for partial response) 15 to <30 kg: 20 mg SUBQ once every 2 weeks (may escalate to weekly for partial response) ≥30 kg: 40 mg SUBQ once every 2 weeks (may escalate to weekly for partial response)	Can be used to treat refractory disease, especially refractory arthritis.
Etanercept	0.8 mg/kg/dose SUBQ once weekly (maximum 50 mg/dose)
Infliximab (patients ≥4 years)	5 to 10 mg/kg/dose IV at weeks 0, 2, and 6, then once every 4 to 8 weeks
Golimumab	Intravenous administration: Dose based on patient weight: 80 mg/m²/dose IV at weeks 0 and 4, then every 8 weeks (maximum 240 mg/dose) Adult dosing: 2 mg/kg /dose at weeks 0 and 4, then every 8 weeks (no defined maximum dose) Subcutaneous administration (no pediatric indication): 50 mg SUBQ once monthly
Other disease-modifying antirheumatic drugs (DMARDs)
Tofacitinib (Janus kinase [JAK] inhibitor; children ≥10 kg)	Dose based on patient weight: 10 to <20 kg: 3.2 mg oral solution twice daily 20 to <40 kg: 4 mg oral solution twice daily ≥40 kg: 5 mg oral solution or immediate-release tablet twice daily (alternative: 11 mg extended-release tablet orally once daily)	Can be used to treat refractory disease.
Abatacept (T-cell costimulatory blocker)	Subcutaneous administration (dose based on patient weight): 10 to <25 kg: 50 mg SUBQ once weekly 25 to <50 kg: 87.5 mg SUBQ once weekly ≥50 kg: 125 mg SUBQ once weekly Intravenous administration (dose based on patient weight): <75 kg: 10 mg/kg IV at weeks 0, 2, and 4, then every 4 weeks 75 to ≤100 kg: 750 mg IV once weekly at weeks 0, 2, and 4, then every 4 weeks >100 kg: 1000 mg IV once weekly at weeks 0, 2, and 4, then every 4 weeks	Can be used to treat refractory disease, especially refractory arthritis. Intravenous dosing is intended for children ≥6 years old.

To be used with UpToDate content on the treatment of sJIA. NOTE: Treatment should be performed by a pediatric rheumatologist who is experienced in the use, monitoring, adjustment, and drug interactions of these agents because of the potential toxicity of these drugs/combinations and the unpredictability of the disease. Dosing in this table is intended for children ≥2 years (except where noted) and adolescents with normal kidney and liver function.

bDMARD: biologic DMARD; IV: intravenous; sJIA: systemic juvenile idiopathic arthritis; SUBQ: subcutaneous.

* Triamcinolone hexacetonide may be preferred to triamcinolone acetonide due to a longer duration of action and milder side effects, however it is not available in the United States and has limited global availability. Refer to UpToDate content on joint injection in children for more details on dosing and administration.

¶ Pulse dose glucocorticoids may be used when rapid control is required for severe symptoms.

Δ For doses of methotrexate doses >10 mg/m², we use divided oral dosing or subcutaneous administration since methotrexate oral absorption decreases with higher doses.

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Therapeutic options for patients with systemic juvenile idiopathic arthritis without macrophage activation syndrome