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

Abstract

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.

Figure 1.

Flowchart showing the number of patients included in the study. MTX, methotrexate; RF+ve poly, rheumatoid factor-positive polyarthritis; RF-ve poly, rheumatoid factor-negative polyarthritis; PSA, psoriatic arthritis; s.c., subcutaneous.

Figure 2.

PedACR 39/50/70/ped90 response rates among oral and s.c. MTX cohorts in the as-observed and intention to treat population. At month 24 of treatment, the response rate was higher in the s.c. cohort in the intention to treat population (P < .0001, HR = 2.6 [1.8-3.7]) for PedACR 30; P < .0001, HR = 2.4 [1.65-3.34]) for PedACR 50; P < .0001, HR = 2.3 [1.64-3.32] for PedACR 70; P < .0001, HR = 2.02 [1.4-2.3] for PedACR 90) obs, observed; ITT, intention to treat; s.c., subcutaneous; HR, hazards ratio.

Figure 3.

Treatment targets JADAS acceptable disease, minimal disease activity, and remission among oral and s.c. MTX cohort in the as-observed and intention to treat population. Only at month 6, statistically significant more patients reached JADAS MDA and JADAS remission upon oral MTX than upon subcutaneous MTX in the as-observed and in the intention to treat population (P = .013, HR = 1.7 [1.1-2.8] and P = .012, HR = 1.78[1.1-2.3]), respectively. JADAS, Juvenile Arthritis Disease Activity Score; MTX, methotrexate; HR, hazards ratio; s.c., subcutaneous.

Figure 4.

Kaplan–Meyer analysis during the first year of treatment. No differences in the kinetics of reaching treatment targets were noted. Obs, observed; s.c., subcutaneous.