Comparative Study of Leflunomide Plus Methotrexate Versus Methotrexate Monotherapy in Refractory Polyarticular Juvenile Idiopathic Arthritis Patients

NCT07428551 | Completed Phase 4 DMC

• 1 other identifier: BSMMU/2024/2965
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized control trial open level and parallel design was conducted in the department of paediatrics, Bangladesh Medical University (BMU). All diagnosed cases of Refractory Polyarticular JIA according to ILAR criteria, unresponsive to MTX were enrolled in this study. After getting written informed consent from the parents/legal guardians, a detailed structured data collection sheet was used for data collection. After enrollment all participants were allocated into experimental group and control group by randomization using random allocation software version 2.0. Total sample size of this study is 50 and 25 participants in each group. All patients of experimental group were given leflunomide along with existing MTX in refractory polyarticular JIA patients and injectable MTX were given at standard dose(15mg/m² BSA) Considering high disease activity steroid were continued in both group at low bridging dose 0.05-1 mg/kg/dose. Patient's disease activity status was assessed by JADAS-27 at initial visit, 6th weeks, 12 weeks and 24 weeks. Functional impairment was assessed by CHAQ-B (DI) at baseline and 24th weeks of treatment. Statistical analysis of the collected data were carried out by using an appropriate statistical tool.

Conditions

Juvenile Idiopathic Arthritis; Polyarticular Juvenile Idiopathic Arthritis; Refractory Polyarticular Juvenile Idiopathic Arthritis

Keywords

CHAQ, JADAS-27, LEF, MTX and and Poly articular JIA

Outcome Measures

Primary Outcomes (1)

• Change in JADAS-27 score from baseline to week 24

  The mean change in Juvenile Arthritis Disease Activity Score-27 (range 0-57) from baseline to week 24. Higher scores indicate greater disease activity

  24 weeks

Secondary Outcomes (5)

• Proportion achieving inactive disease (JADAS ≤1)

  24 weeks

• Proportion achieving low disease activity

  24 weeks

• Mean change in JADAS-27 variables

  24 weeks

• Incidence of adverse events

  24 weeks

• Change in improvement of functional impairment by CHAQ-B(DI)

  24 weeks

Study Arms (2)

Leflunomide plus Methotrexate (Experimental group)

EXPERIMENTAL

Experimental group

Drug: Leflunomide plus Methotrexate

Methotrexate Monotherapy (Control Group)

ACTIVE COMPARATOR

Control group

Drug: Methotrexate Monotherapy

Interventions

Leflunomide plus Methotrexate DRUG

In experimental group, all patients were given leflunomide along with existing methotrexate. Leflunomide was prescribed as once daily oral dose before meal on weight based 10mg for patients 10 to \<20kg, 15mg for patients 20-40kg and 20mg for patients \>40kg. Every medication were purchased from a single pharmaceutical company. Along with leflunomide, all the study participants of this group were received existing MTX subcutaneously at a dose of 15 mg/m2/ week in a single weekly dose. Considering high disease activity level, steroids were continued at low bridging dose at 0.5-1mg/kg/day and then it was stopped by gradually tapering in both group. Nonsteroidal anti-inflammatory drugs were continued as necessary

Leflunomide plus Methotrexate (Experimental group)

Methotrexate Monotherapy DRUG

Participants of control group were given existing MTX subcutaneously at a dose of 15 mg/m²/ week in a single weekly dose at night. Considering high disease activity level, steroids were continued at low bridging dose at 0.5-1mg/kg/day and then it was stopped by gradually tapering in both group. Nonsteroidal anti-inflammatory drugs were continued as necessary.

Methotrexate Monotherapy (Control Group)

Eligibility Criteria

• Age: 1 Day - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All diagnosed cases of Refractory Polyarticular Juvenile Idiopathic Arthritis (JIA) according to ILAR, 2001 unresponsive to methotrexate (at standard dose of 15mg/m² body surface area at least 3-6 months) as monotherapy or together with low dose steroid as bridge therapy who attended Paediatric Rheumatology Division (OPD clinic and inpatient), Department of Paediatrics of BMU, during the study period.

You may not qualify if:

• \. A patient with prior or current infectious disorders, including active/latent tuberculosis, and/or H/O chronic or recurrent severe infections, including opportunistic infections.
• \. A patient with leucopenia (White blood cell count \< 3000/mm3), neutropenia (Neutrophil count \< 1000/mm3) and thrombocytopenia (Platelet count \< 100000/mm3).
• \. Serum creatinine \> upper limit of normal reference range. 4. Alanine aminotransaminase (ALT) more than 2 times of upper normal limit. 5. All diagnosed cases of refractory polyarticular JIA who did not give the consent during the study period.

Sponsors & Collaborators

• Bangladesh Medical University: lead

Study Sites (1)

Bangladesh Medical University

Dhaka, Bangladesh

Location

Related Publications (2)

• Rezaieyazdi Z, Ravanshad S, Khodashahi M, Bokaeian M, Mehrad Majd H, Salari M. Comparison of the efficacy and safety of methotrexate alone or in combination with leflunomide in the treatment of juvenile idiopathic arthritis: a double-blind, placebo-controlled, randomized trial. Reumatologia. 2023;61(1):4-12. doi: 10.5114/reum/161317. Epub 2023 Mar 8.

  PMID: 36998586 BACKGROUND

• Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 2019 Jun;71(6):717-734. doi: 10.1002/acr.23870. Epub 2019 Apr 25.

  PMID: 31021516 BACKGROUND

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

Leflunomide; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Md. Mahbubur Rahman

  Phase B Resident

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Md. Mahbubur Rahman

Model Details: This is a randomized, open-label, parallel-group controlled trial including 50 children with refractory polyarticular juvenile idiopathic arthritis. Participants were randomized in a 1:1 ratio using random allocation software into an experimental group (leflunomide plus methotrexate) and a control group (methotrexate alone), with 25 patients in each group. The experimental group received oral leflunomide once daily (10-20 mg weight-based) in addition to subcutaneous methotrexate 15 mg/m² weekly. The control group received subcutaneous methotrexate 15 mg/m² weekly. Low-dose corticosteroids were allowed as bridging therapy and tapered gradually. NSAIDs were permitted as needed. Follow-up duration was 24 weeks.

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: February 23, 2026
• Study Start: March 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: January 28, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)