Baricitinib, Methotrexate as Monotherapy or Combination in the Treatment of Rheumatoid Arthritis - an Open Label Randomized Clinical Trial

Study Overview
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Brief Summary
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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
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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

Official Title
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Baricitinib, Methotrexate as Monotherapy or Combination in the Treatment of Rheumatoid Arthritis - an Open Label Randomized Clinical Trial

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Baricitinib 2 MG
* Drug: Methotrexate 25mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>baricitinib 2 mg once daily | Drug: Baricitinib 2 MG<br>* baricitinib 2 mg once daily<br>* Other names: Baricitinib 2mg;|
| Active Comparator: Group B<br>methotrexate on 25 mg weekly | Drug: Methotrexate 25mg<br>* 25mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAS 28 ESR | Following parameters are used to evaluate DAS28- Tender joint count Swollen joint count Patient global assessment (vas in cm) ESR/CRP | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical disease activity index (CDAI) | Tender joint count Swollen joint count Patient global assessment (vas in cm) Physician global assessment (vas in cm) | 24 weeks | 
| Health assessment questionnaire disability index (HAQ-DI) | The patient reports the amount of difficulty they have in performing some of these activities like Dressing and grooming, Arising, Eating, Walking, Hygiene, Reach, Grip and Activities. Each question asks on a scale ranging from 0 to 3. If the categories performed without any difficulty (scale 0) up to cannot be done at all (scale 3) | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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baricitinib, rheumatoid arthritis