Correlation Between Beliefs About Medicine and Objective Measures of Efficacy and Safety in Rheumatoid Arthritis (RA)

Study Overview
=================
Brief Summary
-----------------
It can be assumed that there is a link between what the patient feels and thinks about his medication and objective measures of disease activity and safety.

Detailed Description
-----------------
A total of 500 subjects will provide 80% power to test the hypothesis that the absolute value of the correlation between two measures (e.g., BMQ Necessity and DAS28) is ≤ 0.3 (i.e., H0:│r│ ≤ 0.3 ) versus the alternative that it is > 0.3 (i.e., H1:│r │ > 0.3 ) assuming the absolute value of the true correlation is 0.40. A total of 500 will be enrolled to allow for approximately 5% being lost from analysis due to lack of post baseline data. The Pearson method will be used for correlation between the BMQ total score for Necessity and the DAS28 and between the BMQ total score for Concern and DAS28. The Spearman rank method will be used for correlation between the BMQ total scores and Safety. For these latter analyses, subjects will be classified into one of 3 safety categories: (1) No AEs, (2) Non-serious AEs, (3) Serious AEs. 95% confidence intervals for the correlations will be provided.

Official Title
-----------------
Subcutaneous Anti-tnf-αlpha In Rheumatoid Arthritis: Analyze The Correlation Between Objective Measures Of Disease Activity And Safety And A Subjective Measure Such As Patient Beliefs About A Medicine

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

Intervention / Treatment
-----------------
* Other: SC anti-TNF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with RA on stable therapy defined as: Etanercept: 1x50 mg/week or 2x25mg/week for at least 1 consecutive year. Adalimumab: 1x40 mg every other week for at least 1 consecutive year. Oral corticosteroids: stable doses for ≥ 12 weeks before baseline Methotrexate: stable doses for ≥ 12 weeks before baseline Other DMARD's: stable doses for ≥ 12 weeks before baseline Exclusion Criteria: Participation in other clinical or observational trials.

Ages Eligible for Study
-----------------
Minimum Age: 18 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 |
| --- | --- |
| Rheumatoid arthritis patients treated with SC anti-TNF<br> | Other: SC anti-TNF<br>* Subcutaneous (SC) anti-TNF<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Between Beliefs About Medicines Questionnaire (BMQ) Necessity Score and Disease Activity Score Based on 28 Joints Count (DAS28) at Month 12 | Correlation between BMQ necessity and DAS28 was assessed by using Pearson correlation coefficient. BMQ necessity: 5-item scale assessing participant's beliefs about necessity of medications for controlling disease. Participants indicate degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). DAS28: calculated from number of swollen joint count (SJC); tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeter per hour [mm/hour]) and participant's assessment of disease activity (DA) on visual analog scale (VAS) (range 0 [very well] to 100 millimeter (mm) [extremely bad]). DAS28 less than or equal to (<=) 3.2=low DA; greater than (>) 3.2 to <=5.1=moderate DA; >5.1=high DA; <2.6=remission. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Between Beliefs About Medicines Questionnaire Necessity Score and Safety at Month 12 | Correlation between BMQ necessity score and safety was assessed by using Spearman correlation coefficient. BMQ necessity: 5-item scale assessing participant's beliefs about necessity of medications for controlling disease. Participants indicate their degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). Safety was assessed by analyzing the incidence, type and severity of the reported adverse events (AEs) considered related to anti-TNF- alpha therapy. | Month 12 | 
| Correlation Between Beliefs About Medicines Questionnaire Concerns Score and Disease Activity Score Based on 28 Joints Count at Month 12 | Correlation between BMQ concerns score and DAS28 score was assessed by using Pearson correlation coefficient. BMQ concerns is a 6-item scale assessing participant's concerns about potential adverse consequences (range: 1=strongly disagree to 5=strongly agree). Participants indicate their degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). DAS28: calculated from number of SJC; TJC using 28 joints count, ESR (mm/hour) and participant's assessment of DA on VAS (range 0 [very well] to 100 mm [extremely bad]). DAS28 <=3.2= low DA; >3.2 to <=5.1= moderate DA; >5.1=high DA; <2.6=remission. | Month 12 | 
| Correlation Between Beliefs About Medicines Questionnaire Concerns Score and Safety at Month 12 | Correlation between BMQ concerns score and safety was assessed by using Spearman correlation coefficient. BMQ Concerns is a 6-item scale assessing participant's concerns about potential adverse consequences (range: 1=strongly disagree to 5=strongly agree). Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). Safety was assessed by analyzing the incidence, type and severity of the reported AEs considered related to anti-TNF- alpha therapy. | Month 12 | 
| Correlation Between Evolution of Beliefs About Medicines Questionnaire Necessity Score and Disease Activity Score Based on 28 Joints Count | Correlation between evolution of BMQ necessity score and DAS28 score was assessed by calculating Pearson correlation coefficient between change from baseline in DAS28 score and BMQ necessity score at Month 6 and 12. BMQ necessity: 5-item scale assessing participant's beliefs about necessity of medications for controlling disease. Participants indicate their degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). DAS28: calculated from number of SJC; TJC using 28 joints count, ESR (mm/hour) and participant's assessment of DA on VAS (range 0 [very well] to 100 mm [extremely bad]). DAS28 <=3.2= low DA; >3.2 to <=5.1= moderate DA; >5.1=high DA; <2.6=remission. | Month 6, 12 | 
| Correlation Between Evolution of Beliefs About Medicines Questionnaire Necessity Score and Safety | Correlation between evolution of BMQ necessity score and safety was assessed by calculating Spearman correlation coefficient between change from baseline in safety score and BMQ necessity score at Month 6 and 12. BMQ necessity: 5-item scale assessing participant's beliefs about necessity of medications for controlling disease. Participants indicate their degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). Safety was assessed by analyzing the incidence, type and severity of the reported AEs considered related to anti-TNF- alpha therapy. | Month 6, 12 | 
| Correlation Between Evolution of Beliefs About Medicines Questionnaire Concerns and Disease Activity Score Based on 28 Joints Count | Correlation between evolution of BMQ concerns score and DAS28 score was assessed by calculating Pearson correlation coefficient between change from baseline in DAS28 score and BMQ concerns score at Month 6 and 12. BMQ concerns is a 6-item scale assessing participant's concerns about potential adverse consequences (range: 1=strongly disagree to 5=strongly agree). Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). DAS28: calculated from number of SJC; TJC using 28 joints count, ESR (mm/hour) and participant's assessment of DA on VAS (range 0 [very well] to 100 mm [extremely bad]). DAS28 <=3.2= low DA; >3.2 to <=5.1= moderate DA; >5.1=high DA; <2.6=remission. | Month 6, 12 | 
| Correlation Between Evolution of Beliefs About Medicines Questionnaire Concerns and Safety | Correlation between evolution of BMQ concerns score and safety was assessed by calculating Spearman correlation coefficient between change from baseline in BMQ concerns score and safety score at Month 6 and 12. BMQ concerns is a 6-item scale assessing participant's concerns about potential adverse consequences (range: 1=strongly disagree to 5=strongly agree). Scores obtained for individual items were summed, divided by total number of items and multiplied by 5 to give total score ranging from 5 to 25 (higher scores=stronger beliefs). Safety was assessed by analyzing the incidence, type and severity of the reported AEs considered related to anti-TNF- alpha therapy. | Month 6, 12 | 
| Percentage of Participants Agreeing or Strongly Agreeing With Beliefs About Medicines Questionnaire at Baseline | BMQ consists of two 5-item scales assessing participants' agreement or strong agreement with beliefs about BMQ necessity and BMQ concerns. The items were: BMQ1: Necessity (my health at present depends on my medicines); BMQ2: Concern (having to take medications worries me); BMQ3: Necessity (my life would be impossible without my medications); BMQ4: Concern (I sometimes worry about the long term effects of my medications); BMQ5: Necessity (without my medications I would be very ill); BMQ6: Concern (my medications are mystery to me); BMQ7: Necessity (my health in the future will depend on my medications); BMQ8:Concern (my medications disrupt my life); BMQ9: Necessity (I sometimes worry about becoming too dependent on my medications); BMQ10: Concern (my medications protect me from becoming worse); BMQ11: Necessity (these medicines cause to me unpleasant adverse events). | Baseline | 
| Percentage of Participants Agreeing or Strongly Agreeing With Beliefs About Medicines Questionnaire at Month 6 and 12 | BMQ consists of two 5-item scales assessing participants' agreement or strong agreement with beliefs about BMQ necessity and BMQ concerns. The items were: BMQ1: Necessity (my health at present depends on my medicines); BMQ2: Concern (having to take medications worries me); BMQ3: Necessity (my life would be impossible without my medications); BMQ4: Concern (I sometimes worry about the long term effects of my medications); BMQ5: Necessity (without my medications I would be very ill); BMQ6: Concern (my medications are mystery to me); BMQ7: Necessity (my health in the future will depend on my medications); BMQ8:Concern (my medications disrupt my life); BMQ9: Necessity (I sometimes worry about becoming too dependent on my medications); BMQ10: Concern (my medications protect me from becoming worse); BMQ11: Necessity (these medicines cause to me unpleasant adverse events). | Month 6, 12 | 
| Change From Baseline in Percentage of Participants Agreeing or Strongly Agreeing With Beliefs About Medicines Questionnaire at Month 12 | BMQ consists of two 5-item scales assessing participants' agreement or strong agreement with beliefs about BMQ necessity and BMQ concerns. The items were: BMQ1: Necessity (my health at present depends on my medicines); BMQ2: Concern (having to take medications worries me); BMQ3: Necessity (my life would be impossible without my medications); BMQ4: Concern (I sometimes worry about the long term effects of my medications); BMQ5: Necessity (without my medications I would be very ill); BMQ6: Concern (my medications are mystery to me); BMQ7: Necessity (my health in the future will depend on my medications); BMQ8:Concern (my medications disrupt my life); BMQ9: Necessity (I sometimes worry about becoming too dependent on my medications); BMQ10: Concern (my medications protect me from becoming worse); BMQ11: Necessity (these medicines cause to me unpleasant adverse events). | Baseline, Month 12 | 
| Pearson Correlation Coefficient Between Beliefs About Medicines Questionnaire and Medication Adherence Rating Scale (MARS) at Baseline | BMQ Necessity and BMQ Concerns are described in outcome measure 1 and 2 respectively. BMQ necessity-concerns: difference between necessity and concerns scales (ranges from -20 to +20, where higher score=better cost-benefit). BMQ Harm scale assesses the degree to which medicines are perceived as harmful. BMQ over use scale assesses beliefs about use of medicines and if they are overprescribed by clinicians. BMQ Harm and overuse scales comprise of 4 items, each item assessed on a 5-point scale (1=strongly disagree to 5=strongly agree). Total BMQ Harm and overuse scores were calculated as the sum of individual items and ranges from 4 to 20. Higher scores =more negative orientation towards medicines. MARS consists of a 5-item scale assessing the frequency of non-adherent behavior of participants for taking medication (5=never, 4=rarely, 3=sometimes, 2=often, 1=very often). Scores for each of the 5 items were summed; ranging from 5 to 25. Higher scores=higher levels of adherence. | Baseline | 
| Pearson Correlation Coefficient Between Beliefs About Medicines Questionnaire and Medication Adherence Rating Scale at Month 6 and 12 | BMQ Necessity and BMQ Concerns are described in outcome measure 1 and 2 respectively. BMQ necessity-concerns: difference between necessity and concerns scales (ranges from -20 to +20, where higher score=better cost-benefit). BMQ Harm scale assesses the degree to which medicines are perceived as harmful. BMQ over use scale assesses beliefs about use of medicines and if they are overprescribed by clinicians. BMQ Harm and overuse scales comprise of 4 items, each item assessed on a 5-point scale (1=strongly disagree to 5=strongly agree). Total BMQ Harm and overuse scores were calculated as the sum of individual items and ranges from 4 to 20. Higher scores =more negative orientation towards medicines. MARS consists of a 5-item scale assessing the frequency of non-adherent behavior of participants for taking medication (5=never, 4=rarely, 3=sometimes, 2=often, 1=very often). Scores for each of the 5 items were summed; ranging from 5 to 25. Higher scores=higher levels of adherence. | Month 6, 12 | 
| Correlation Between Demographic and Clinical Factors and Beliefs About Medicines Questionnaire Necessity Score at Baseline | Correlation between BMQ necessity score and participant's characteristics (demography and clinical factors) was assessed by using Pearson correlation coefficient. BMQ consists of two 5-item scales assessing participants' beliefs about necessity of prescribed medication for controlling disease (BMQ necessity) and their concerns about potential adverse consequences of taking it (BMQ concerns). Respondents indicate their degree of agreement with each statement on five-point Likert scale, ranging from 1=strongly disagree to 5=strongly agree. Total scores for necessity and concerns scales were summed; range from 5 to 25. Higher scores = stronger beliefs. Participant's characteristics included age, height, weight, body mass index (BMI), time since first RA symptoms, diagnosis, number of comorbidities and number of joint replacement or surgery. | Baseline | 
| Correlation Between Demographic and Clinical Factors and Beliefs About Medicines Questionnaire Concerns Score at Baseline | Correlation between BMQ concerns score and participant's characteristics (demography and clinical factors) was assessed by using Pearson correlation coefficient. BMQ consists of two 5-item scales assessing participants' beliefs about necessity of prescribed medication for controlling disease (BMQ necessity) and their concerns about potential adverse consequences of taking it (BMQ concerns). Respondents indicate their degree of agreement with each statement on five-point Likert scale, ranging from 1=strongly disagree to 5=strongly agree. Total scores for necessity and concerns scales were summed; range from 5 to 25. Higher scores = stronger beliefs. Participant's characteristics included age, height, weight, BMI, time since first RA symptoms, diagnosis, number of comorbidities and number of joint replacement or surgery. | Baseline |