Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, Active
Brief summary
To use different starting doses of methotrexate (7.5 mg per week) versus 15 mg per week in patients with rheumatoid arthritis, followed by similar hiking up of dose (2.5 mg per 2 weeks, till max of 25 mg per week). To look at the effect on efficacy ( or speed of efficacy) versus the adverse effects. Hypothesis: There will be no difference in the adverse effects, but better and faster control of disease when starting with a higher methotrexate dose
Interventions
DRUGMethotrexate
Different doses for both arms followed by similar escalation (2.5 mg every 15 d) till max of 25 mg per week or 3 months completed
Sponsors
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with rheumatoid arthritis fulfilling the ACR 1987 criteria * Between 18 years to 65 year of age * Having active disease Disease activity score (28 joints) DAS28-3 more than 5.1 * Not on methotrexate in the last 2 months * Permitted to be on corticosteroids if the dosages stable for at least 1 weeks before randomization and if corticosteroid dosage less than 10 mg/day * Permitted to be on other disease modifying anti-rheumatic drug (DMARD) like sulfasalazine, leflunomide and hydroxychloroquine, if dosages stable for at least 2 weeks before randomization
Exclusion criteria
* Pregnant/Breastfeeding * Ongoing/Recent treatment with methotrexate (2 months) * Chronic liver disease * Renal failure * Any leucopenia or thrombocytopenia * Breast-feeding * Desirous of pregnancy in the next 6 months * Known Hepatitis B or C positive * Known clinically relevant chronic lung disease: ILD * Tuberculosis or other active infections * Known HIV positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the DAS28-3 (Disease Activity Score Using 28 Joints and Using 3 Variables) - Difference Between This Score at 12 Weeks and This Score at Baseline | 12 weeks | DAS28-3 is disease activity score using 28 joints and using 3 variables (tender and swollen joint count for 28 joints and ESR(westergren 1st hour) It ranges from 0 to 9.3 where a lower value implies lower disease activity |
| Patients With Good Response (Final DAS28-3 Less Than 3.2 and Fall More Than 1.2) | 3 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Patients Who Withdrew Because of Any Cause | 3 months |
| Proportion Requiring Stoppage/Decrease/Inability to Hike MTX Due to Cytopenia or Transaminitis (SGOT or SGPT More Than 80IU) | 3 months |
| Proportion Who Withdrew Due to Intolerance | 3 months |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methotrexate 7.5 mg Per Week Patients started on 7.5 mg of oral methotrexate (weekly) which was then escalated by 2.5 mg every 2 weeks (max 25 mg weekly) | 47 |
| Methotrexate 15 mg Per Week Patients started on 15 mg of oral methotrexate (weekly) which was then escalated by 2.5 mg every 2 weeks (max 25 mg weekly) | 53 |
| Total | 100 |
Baseline characteristics
| Characteristic | Methotrexate 7.5 mg Per Week | Methotrexate 15 mg Per Week | Total |
|---|---|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 10.3 | 42.8 years STANDARD_DEVIATION 11.2 | 43.6 years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 37 Participants | 41 Participants | 78 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 47 | 22 / 53 |
| serious Total, serious adverse events | 0 / 47 | 0 / 53 |
Outcome results
Primary
Mean Change in the DAS28-3 (Disease Activity Score Using 28 Joints and Using 3 Variables) - Difference Between This Score at 12 Weeks and This Score at Baseline
DAS28-3 is disease activity score using 28 joints and using 3 variables (tender and swollen joint count for 28 joints and ESR(westergren 1st hour) It ranges from 0 to 9.3 where a lower value implies lower disease activity
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methotrexate 7.5 mg Per Week | Mean Change in the DAS28-3 (Disease Activity Score Using 28 Joints and Using 3 Variables) - Difference Between This Score at 12 Weeks and This Score at Baseline | -0.47 units on a scale | Standard Deviation 0.86 |
| Methotrexate 15 mg Per Week | Mean Change in the DAS28-3 (Disease Activity Score Using 28 Joints and Using 3 Variables) - Difference Between This Score at 12 Weeks and This Score at Baseline | -0.55 units on a scale | Standard Deviation 0.79 |
p-value: 0.695% CI: [-0.26, 0.54]t-test, 2 sided
Primary
Patients With Good Response (Final DAS28-3 Less Than 3.2 and Fall More Than 1.2)
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate 7.5 mg Per Week | Patients With Good Response (Final DAS28-3 Less Than 3.2 and Fall More Than 1.2) | 0 participants |
| Methotrexate 15 mg Per Week | Patients With Good Response (Final DAS28-3 Less Than 3.2 and Fall More Than 1.2) | 1 participants |
Secondary
Proportion of Patients Who Withdrew Because of Any Cause
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate 7.5 mg Per Week | Proportion of Patients Who Withdrew Because of Any Cause | 9 participants |
| Methotrexate 15 mg Per Week | Proportion of Patients Who Withdrew Because of Any Cause | 7 participants |
Secondary
Proportion Requiring Stoppage/Decrease/Inability to Hike MTX Due to Cytopenia or Transaminitis (SGOT or SGPT More Than 80IU)
Time frame: 3 months
Secondary
Proportion Who Withdrew Due to Intolerance
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate 7.5 mg Per Week | Proportion Who Withdrew Due to Intolerance | 2 participants |
| Methotrexate 15 mg Per Week | Proportion Who Withdrew Due to Intolerance | 2 participants |