Children with arthritis: monotherapy or polytherapy?

Rationale: Initial disease modifying antirheumatic drug (DMARD) therapy with methotrexate in the

treatment of juvenile idiopathic arthritis (JIA) has a low efficacy. For this reason, it has been

proposed that TNF-inhibitors may be used as a first-line treatment. The response to TNF inhibitors is

often more rapid, but the treatment has the downside of parenteral use and high costs. In adults

with rheumatoid arthritis, polytherapy with a combination of DMARDs has been proven to be very

effective. We therefore propose that polytherapy with methotrexate, sulfasalazine and

hydroxychloroquine could be beneficial for children with juvenile idiopathic arthritis who require

DMARD therapy.

Primary objectives: To study whether polytherapy (methotrexate, sulfasalazine and

hydroxychloroquine) results in more patients with inactive disease and therefore less patients that

need treatment with a TNF inhibitor after 6 months of treatment compared to primary MTX

monotherapy in children with newly diagnosed JIA.



Secondary objectives:

- To compare side effects and tolerability of treatment in both treatment arms

- To compare the number of patients that are treated with a TNF inhibitor after 12 months of

treatment in both arms

- To compare the number of patients that need to switch to subcutaneous MTX after 3 months of

treatment in both treatment arms

- To compare ACR Pedi scores (30, 50, 70, 90) and JADAS scores in both treatment groups at 3, 6, 9,

and 12 months and the number of patients with inactive disease at 3, 9 and 12 months of treatment

- To compare functional ability and quality of life in both treatment arms


- To provide cost-effectiveness data concerning the first year of DMARD therapy in both groups



Study design: A multicenter, single-blinded, randomized, treat to target, one-year follow-up clinical

trial in patients with recent onset JIA.



Study population: Children (2-16 years old) with JIA and active disease.

Intervention: Patients are randomly assigned to one of two treatment strategies: monotherapy with

methotrexate (in combination with prednisolone bridging) or polytherapy with methotrexate,

sulfasalazine and hydroxychloroquine (in combination with prednisolone bridging). When

improvement is not sufficient after 3 months of treatment (according to JADAS10 cut-off values),

methotrexate will be switched to subcutaneous administration in either strategy. When at 6 months

inactive disease (according to modified Wallace criteria1) is not reached, a TNF-inhibitor will be

started.

Main study endpoint: The number of patients with inactive disease after 6 months of treatment.



Nature and extent of the burden and risks associated with participation, benefit and group

relatedness: This study focuses on the treatment of JIA and can therefore only be performed in

children (2-16 years old). During the study, blood sampling and visits to the outpatient clinic are part

of regular care. The side effects of polytherapy are expected to be similar or slightly increased

compared to methotrexate monotherapy. Polytherapy may lead to earlier achievement of inactive

disease and therefore no need to administer methotrexate subcutaneously or to switch to

(subcutaneous) biologic treatment.

Combinationtherapy with methotrexate, sulfasalazine en hydroxychloroquine will result in more patients with inactive disease and therefore less patients that need an TNF-inhibitor after 6 months of treatment than treatment with methotrexate alone in children with recently diagnosed juvenile idiopathic arthritis.

baseline, 3,6,9 and 12 months

Arm 1: methotrexate monotherapy

Arma 2: combination therapy with methotrexate, sulfasalazine en hydroxychloroquine