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Table 1 Drug recommendation and dosing (Level of evidence grading according to Burns et al. [30])

From: Protocols on classification, monitoring and therapy in children’s rheumatology (PRO-KIND): results of the working group Polyarticular juvenile idiopathic arthritis

Non-Steroidal-Anti-Inflammatory Drugs (NSAIDs) No prolonged monotherapy with NSAIDs (without corticosteroid injections) in patients with active arthritis.
NSAID monotherapy (without additional therapy) for longer than 2 months is unsuitable for patients with active arthritis, regardless of the presence of parameters indicating poor prognosis.
Approval status and dosages have to be considered:Naproxene, 10–15,mg/kg bw, tablets approved from 12 years, juice formulation age limit >1 year.
Ibuprofen, 30–40 mg/kg bw, approved from age 6 months.
Indometacine, 2–3 mg/kg bw, approved from age 2 years, juice formulation available
Diclofenac, 2–3 mg/kg bw, approved from age 9 years
Meloxicam, 0,25–0,375 mg/kg bw, not approved or JIA, approved for Rheumatoid Arthritis, Ankylosing Spondylitis and arthrosis if age is >16 years
Celecoxib, 6–12 mg/kg bw, not approved for JIA in Germany, approved in the USA for children 2 years of age
Systemic corticosteroids Systemic high-dose corticosteroid therapy can be indicated in the presence of significant immobilizing disease activity.
A systemic low-dose corticosteroid therapy can be used in long-term therapy, e.g. can be indicated in the presence of considerable morning stiffness.
Intravenous high-dose steroid pulse therapy may be initially indicated for high disease activity, immobilizing disease and critical extra-articular manifestations.
Short term highly dosed corticosteroids (considerable immobilizing disease activity) Prednisone, Prednisolone or Methylprednisolone at a dosage up to 2 mg/kg bw daily (up to 60 mg) in 3 ED for about 2 weeks, followed by tapering of the dosage about 25% per week over the next 4–8 weeks.
Low dosed corticosteroids (in long-term therapy, for example, with severe morning stiffness) <0,15 mg/kg bw, probably alternate day <0,2 mg/kg bw every 48 h.
Corticosteroid Pulse Therapy (with high disease activity, immobilizing disease, critical extra-articular manifestations) Methylprednisolone, 10-30 mg/kg (up to 1000) as infusion on 3 consecutive days. To be repeated after 2–4 weeks.
Intraarticular corticosteroids Intraarticular corticosteroid therapy may be indicated for any joint with active arthritis. It may be used as an initial therapy, as a component or in addition to other therapies. Injections can be repeated in several months intervals; Triamcinolone hexacetonide (TH) is preferable to other preparations. TH 0.5-1 mg / kg bw can be used in large joints (knee, hip, shoulder), up to 0.5 mg / kg bw in medium-sized joints (hand jump, elbow joints) and up to 2 mg in small joints (finger or toe).
Methotrexate The use of methotrexate has been justified by a double-blind placebo-controlled study of polyarticular JIA with evidence level 1A [13]. It is indicated for all patients if after the initial diagnostic phase active polyarthritis is present. Application can be orally or s.c. at a dosage of 10–20 mg / m2 / once per week. Additionally folic acid 5 mg, 1 / week, 24 h after methotrexate is optional.
Sulfasalazine The use of sulfasalazine can be justified with evidence level 2 because of the results of a double-blind placebo-controlled study in polyarticular juvenile arthritis [14]. Is is recommended only for HLA-B27 positive patients, possibly indicated in combination with MTX. The target dosage of 30–50 mg/kg/day is stepwise reached by increase from 10 mg/kg over 2–4 weeks.
Hydroxychloroquine The use of hydroxychloroquine can be justified on the results of a double-blind placebo-controlled study in polyarticular juvenile arthritis with evidence level 2 [15]. Dosage 5–7 mg/kg based on ideal weight It is not indicated as monotherapy and in exceptional cases in combination with methotrexate.
Leflunomide The use of leflunomide can be justified with the evidence level 2 because of a double-blind, controlled study with inconclusive results in polyarticular juvenile arthritis [16]. Not approved for treatment of JIA, therefore not recommended for therapy. Dosage in children up to 20 kg body weight 10 mg daily, 20 mg kg body weight 15 mg daily and 20 mg in over 40 kg body weight.
Etanercept The use of etanercept is justified by a double-blind, placebo-controlled study in polyarticular juvenile arthritis with the evidence level 1B [1]. Dosage 2 × 0.4 mg or 1 × 0.8 mg / week or 0.8 mg / kg / week in 1–2 injections with a maximum weekly dosage of 50 mg.
Adalimumab The use of adalimumab can be justified by a double-blind, placebo-controlled study in polyarticular juvenile arthritis with the evidence level 1B [2]. Up to age of 13 years the dosage is 24 mg / m2 every 2 weeks, maximum 40 mg / injection, from 13 years on 40 mg / 2 weeks, in exceptional cases 40 mg / week.
Tocilizumab The use of tocilizumab is justified by a double-blind, placebo-controlled study in polyarticular juvenile arthritis (level 1B) [3]. The dosage i.v. is 10 mg / kg / 4 weeks if body weight is <30 kg. and 8 mg / kg / 4 weeks if body weight ≥ 30 kg up to 800 mg / application.
Abatacept The use of abatacept is justified by a double-blind, placebo-controlled study in polyarticular juvenile arthritis with evidence level 1 [4]. The drug is approved after failure of TNF inhibitors only. An iv dosage of 10 mg / kg at week 0, 2 and 4; then every 4 weeks is recommended.
Golimumab The use of golimumab is justified with the evidence level 2 (15) due to a single inconclusive double-blind, placebo-controlled study in polyarticular juvenile arthritis (15). Dosage: 50 mg/m2 s.c. every 4 weeks for adolescents with polyarthritis with a body weight of 40 kg. Obligatory combination with methotrexate.