Assessment of Clinical Effectiveness and Safety of Adalimumab and High Dose Methotrexate in Routine Clinical Practice

Study Overview
=================
Brief Summary
-----------------
This was a single-arm, multicenter, open label, prospective cohort study (post-marketing observational study) to determine the effectiveness and safety of adalimumab in combination with high-dose methotrexate (≥12 mg/week) in participants with rheumatoid arthritis in a routine clinical setting in Japan.

Detailed Description
-----------------
Study assessments occurred at baseline, Week 12, Week 24, Week 52, Week 76, and Week 104. Most participants received 40 mg of adalimumab every other week during the study. Two participants started at 40 mg of adalimumab every other week, and increased to 80 mg every other week. A few participants had a different dose regimen: 40 mg every three weeks for 3 participants; 40 mg every four weeks for 1 participant; and 40 mg every other week with a switch to 50 mg every three weeks for 4 subjects.

Official Title
-----------------
Assessment of Clinical Effectiveness and Safety of Adalimumab and High Dose Methotrexate in Routine Clinical Practice (Combo Study; Adalimumab With High Dose MTX)

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Adalimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The participants of this study were rheumatoid arthritis (RA) patients for whom adalimumab was prescribed. They must have met the following conditions: Disease duration of RA ≤2 years Methotrexate (MTX) administration ≥3 months prior to starting adalimumab Dose of MTX ≥12mg/week Disease Activity Score 28 (DAS28)-C-reactive protein (CRP) score >3.2 Exclusion Criteria: Participants who had been previously treated with biologics (including tumor necrosis factor [TNF] inhibitors and others)

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants treated with adalimumab<br>40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks | Drug: Adalimumab<br>* Pre-filled syringe, administered by subcutaneous injection<br>* Other names: ABT-D2E7;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Disease Activity Score 28 (DAS28) Score of <2.6 at Week 52 | The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hr) or C-reactive protein (CRP; mg/dL) level, and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Clinical Disease Activity Index (CDAI) Score ≤ 2.8 at Week 104 | The Clinical Disease Activity Index (CDAI) is a composite index for assessing rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the participant's global assessment of disease activity (on a visual analog scale [VAS] from 0 to 10 cm), and a physician's global assessment of disease activity (measured on a VAS from 0 to 10 cm) are summed to yield the total score. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Remission is defined as a CDAI score ≤ 2.8. | At Week 104 | 
| Percentage of Participants With a Simplified Disease Activity Index (SDAI) Score ≤ 3.3 at Week 104 | The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm), global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (CRP; mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86. An SDAI score ≥26.1 indicates high disease activity, an SDAI score between 11.1 and 26.0 indicates moderate disease activity, an SDAI score between 3.4 and 11.0 indicates low disease activity, and an SDAI score ≤3.3 indicates clinical remission. | At Week 104 | 
| Percentage of Participants With a Health Assessment Questionnaire Disability Index (HAQ-DI) Score < 0.5 at Week 104 | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a self-reported assessment specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. HAQ remission indicating normal physical function is defined as HAQ-DI < 0.5. | At Week 104 | 
| Mean Change From Baseline in European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) Index Score at Week 104 | The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: no problems (1), some problems (2), extreme problems (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. | Baseline and Week 104 | 
| Percentage of Participants With a Change From Baseline of ≤ 1.0 in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 104 | The van der Heijde modified Total Sharp Score (mTSS) is a measure of the level of joint damage. X-rays of hands and feet were taken at the visit. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. | Baseline and Week 104 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rheumatoid arthritis, Methotrexate