European Journal of Rheumatology
Original Article

Oral or Parenteral Methotrexate for the Treatment of Polyarticular Juvenile Idiopathic Arthritis


Pediatric and Pediatric Rheumatology Consultant, East Jeddah Hospital, Jeddah, Saudi Arabia


Medical faculty department of Paediatrics, University of Cologne, Cologne, Germany


Department of General Peadiatric, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany


Department of Paediatric and Adolescent Medicine, Univerity Hospital of Cologne, Cologne, Germany

Eur J Rheumatol 2022; 9: 197-205
DOI: 10.5152/eurjrheum.2022.21090
Read: 1166 Downloads: 417 Published: 10 May 2022

Objective: Subcutaneous methotrexate injections are considered to be more effective or work faster than oral methotrexate. Therefore, the extent and the kinetics of response were analyzed in juvenile idiopathic arthritis patients treated with oral versus subcutaneous methotrexate.

Methods: The BIKER databank was searched for biologics-naive juvenile idiopathic arthritis patients treated with methotrexate as initial treatment. The Juvenile Arthritis Disease Activity Score-10 defini- tion of remission and the pediatric American College of Rheumatology's response parameters were utilized as outcome criteria.

Result: A total of 410 polyarticular juvenile idiopathic arthritis patients receiving oral methotrexate were compared to 384 patients receiving subcutaneous methotrexate. Rheumatoid factor-negative polyarthritis was the most common juvenile idiopathic arthritis category (50%/51%) in this cohort followed by extended oligoarthritis (27%/26%), polyarticular psoriatic arthritis (18%/16%), and few had rheumatoid factor-positive polyarthritis (5%/8%). The oral cohort’s disease duration (2.3 ± 3.0 vs. 1.9 ± 2.7) was significantly longer (P=.04), although their age at onset and baseline were similar. Furthermore, at baseline, disease activity (Juvenile Arthritis Disease Activity Score-10 16.5 ± 7.2 vs. 14.7 ± 8.2; P = .001 due to a higher active joint count 9.0 ± 10.1 vs. 7.4 ± 7.7; P = .011) was higher in the subcutaneous cohort. The weekly methotrexate doses were comparable with 13.6 ± 5.4 mg/m2 and 13.3 ± 4.5 mg/m2, respectively. 
With oral/subcutaneous methotrexate, a pediatric American College of Rheumatology’s 90 was achieved in 98(38.3%)/128(40.4%), while 96(38.1 %)/75(40.1%) attained Juvenile Arthritis Disease Activity Score remission after 12 months of therapy. There was no difference in the early kinetics of response according to Kaplan–Meyer analysis. 
Adverse events including nausea, vomiting, and increased transaminases were considerably more common after methotrexate subcutaneous administration than after oral treatment.

Conclusion: In terms of effectiveness, but not safety, our retrospective analysis found some advan- tages of subcutaneous methotrexate. Adverse effects limit treatment continuance and thus must be considered a disadvantage. Furthermore, oral methotrexate eliminates the need for injections, which is especially essential for younger children. Controlled, randomized prospective trials in children and juvenile patients are necessary for definitive recommendations for the subcutaneous route of admin- istration of methotrexate therapy.

Cite this article as: Bakry R, Klein MA, Horneff G. Oral or parenteral methotrexate for the treatment of polyarticular juvenile idiopathic arthritis. Eur J Rheumatol. 2022;9(4):197-205.

EISSN 2148-4279