Clinical trial NCT05827497: Baricitinib, Methotrexate as Monotherapy or Combination in the Treatment of Rheumatoid Arthritis - an Open Label Randomized Clinical Trial
Official title: Baricitinib, Methotrexate as Monotherapy or Combination in the Treatment of Rheumatoid Arthritis - an Open Label Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: baricitinib, rheumatoid arthritis
Lead sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Sponsor class: OTHER
First posted: 2023-04-25
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this open-label randomized clinical trial is to assess the efficacy of baricitinib 2 mg in comparison to methotrexate 25 mg as monotherapy followed by baricitinib 4 mg in comparison to methotrexate 10 mg and baricitinib 2 mg combination in patients with rheumatoid arthritis with moderate to severe disease activity. The main question it aims to answer:

• Is there any difference in the efficacy of baricitinib as monotherapy in comparison to methotrexate monotherapy or methotrexate-baricitinib combination in the treatment of rheumatoid arthritis

Detailed description: This open-label randomized clinical trial will be conducted in the department of rheumatology, BSMMU. The rheumatoid arthritis patients with moderate to high disease activity at baseline, disease activity score (DAS28ESR\>3.2) will be considered as primary entry criteria for this study. Consecutive sampling method will be applied. The study will be done in 2 phases, duration of each phase 24 weeks. Considering inclusion and exclusion criteria, total 132 patients are randomized into group A and group B following block randomization. Each group will be consisting of 66 patients. In phase 1 Group A will be put on baricitinib 2 mg once daily and Group B will be put on methotrexate 25 mg weekly. The patients who fail to achieve remission or low disease activity by 24 weeks eligible for entry into phase 2 where group A will be put on baricitinib 4 mg and group B will be put on baricitinib 2 mg in combination with methotrexate 10 mg. Follow-up will be done at the 4th, 12th and 24th week in phase 1 and 28th, 36th and 48th week in phase 2. Response to treatment will be evaluated by DAS 28 ESR. At the end of 24th week endpoint for efficacy will be assessed at by DAS 28ESR. Adverse effects will be assessed by history, physical examinations and investigations.

Results will be compared among two groups with a 95% confidence interval and a p-value of \< 0.05. The degrees of statistical significance between groups will be analyzed by unpaired t-test and/or Mann-Whitney U test. Qualitative data in between groups will be analyzed by the chi-square test. Probabilities of associations will be assessed by calculating Spearman´s rank correlation coefficient

Eligibility criteria: Inclusion Criteria:

* 1. Patients more than 18 years of age 2. Patients fulfill the ACR/EULAR 2010 classification criteria for Rheumatoid arthritis 3. Patients with DAS 28 ESR\> 3.2

Exclusion Criteria:

* 1. Recent or concurrent infection including active tuberculosis 2. Haemoglobin (Hb) \< 9 gm/dl 3. Total WBC count \< 4000 / µL 4. Neutrophil count \< 1200 / µL 5. Lymphocyte count \< 750 / µL 6. AST/ALT \> three times the upper limit of normal 7. Estimated glomerular filtration rate \< 60 ml/minute/1.73 m2 8. Co-morbid illness- e.g., Malignancy 9 . Pregnant or breast feeding woman

Primary outcomes:
measure: DAS 28 ESR
timeFrame: 24 weeks
Secondary outcomes:
measure: Clinical disease activity index (CDAI)
timeFrame: 24 weeks
measure: Health assessment questionnaire disability index (HAQ-DI)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Dr. Md. Abu Shahin
Study officials:
affiliation: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
name: Dr. Md Abu Shahiin, FCPS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fleischmann R, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, Zerbini CA, Gurbuz S, Dickson C, de Bono S, Schlichting D, Beattie S, Kuo WL, Rooney T, Macias W, Takeuchi T. Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment. Arthritis Rheumatol. 2017 Mar;69(3):506-517. doi: 10.1002/art.39953.
citation: Islam N, Baron Basak T, OudeVoshaar MA, Ferdous N, Rasker JJ, Atiqul Haq S. Cross-cultural adaptation and validation of a Bengali Health Assessment Questionnaire for use in rheumatoid arthritis patients. Int J Rheum Dis. 2013 Aug;16(4):413-7. doi: 10.1111/1756-185X.12032. Epub 2013 Jan 22.
citation: Yamaoka K. Janus kinase inhibitors for rheumatoid arthritis. Curr Opin Chem Biol. 2016 Jun;32:29-33. doi: 10.1016/j.cbpa.2016.03.006. Epub 2016 Mar 17.