The Correlation Between Medication Adherence and Disease Activity in Adult Patients with Rheumatoid Arthritis Receiving Care

at a Specialty Pharmacy
Michael W. Crowe1, Ho-Cheong S. Lee2, Heidi M. Michels1, Chris Y. Baek1, Mark S. Chaffee1
1Diplomat

Specialty Pharmacy, Grand Rapids, MI; 2Ferris State University, Grand Rapids, MI

Background
In patients with rheumatoid arthritis (RA), non-adherence to and non-persistence with disease modifying antirheumatic drugs (DMARDs) is prevalent (20-70%).1 Low adherence results in poor health outcomes, improper assessment of efficacy, and increased healthcare costs. It also contributes to treatment failure, delayed disease recovery, accelerated disease progression, and the need for more aggressive treatment. Treatment failure rates are lower in patients with higher adherence.2-5 Improved adherence has been demonstrated in patients with RA receiving: Satisfactory contact with healthcare professionals6 Disease and treatment education6 Pharmacist interventions, such as telephone calls, to discuss adherence or medication-related problems7 Diplomat Specialty Pharmacy has previously established a drug therapy management program (DTM) for patients with RA.

Patients
Eligibility Criteria 1. Patient > 18 years of age diagnosed with RA 2. Receive FDA-approved doses of either adalimumab or etanercept, for the treatment of RA, for > 12 months from this specialty pharmacy 3. Competent (i.e. responsible for their own healthcare) 4. No record of receiving previous biologic DMARD therapy within 4 weeks of enrollment into the DTM program 5. Enrolled between June 1, 2008 and February 28, 2010 6. No biologic-free periods lasting greater than 4 weeks 7. At least 1 score available for each survey (HAQ-II, NRS) Exclusion Summary 284 patients met eligibility criteria 1 through 5 above. 87 were excluded for having a drug-free period > 4 weeks. 107 were excluded for missing outcomes data. Patients Eligible for Evaluation

Results
n 90 Mean MPR [range] 0.939 [0.687-1] Mean HAQ-II Score [range] 0.56 [0-2.2] Mean Pain Score [range] 3.1 [0-10] Mean Fatigue Score [range] 3.1 [0-10]

6-Month Outcomes

51

12-Month Outcomes

58

Objective
To determine the correlation between medication adherence to biologic therapy and patient-reported measures of disease activity, after the initiation of therapy in patients with RA, receiving care from this community-based specialty pharmacy.
Mean Age (range) % Female

Overall Adalimumab Etanercept Switched (n = 90) (n = 30) (n = 54) (n = 6) 54 52 56 46 (20-75) (51-75) (30-73) (20-69) 70% 60% 72% 100%

Discussion
Despite the burden of added time for the patient and elevated operational costs for the pharmacy, measures of disease activity at 6 or 12 months were collected by the pharmacy team for nearly half of the patients meeting the eligibility criteria. 107 patients were excluded because either their records did not contain recorded outcomes or they were not recorded at the correct interval of 6 and 12 months. Patients levels of medication adherence met our expectations and are likely attributable to the steps built into the DTM program. Our findings for the correlation between medication adherence and HAQ-II scores is consistent with our expectation that a higher MPR would correlate with a lower HAQ-II score, however a correlation between adherence and pain and fatigue was not found. Study Limitations Single-center study Small sample size Limited availability of data Samples were not identical at 6 and 12 months

Conclusions
An increase in MPR shows a slight correlation with a decrease in HAQ-II score, more so at 6 months than at 12. A correlation for pain and fatigue with MPR was not demonstrated. Inconsistencies in data collection may warrant closer monitoring by pharmacy administrative staff, in order to achieve the full potential of this DTM program. These results provide some insights on the relationship between RA drug therapy adherence and measures of disease activity. This not only offers community pharmacies opportunities to improve patient care, but also provides valuable data for this pharmacys assessment of its current DTM program.

Indicates patients that switched from adalimumab to

etanercept (or vice versa), during their enrollment period

Methods
Drug Therapy Management Program Patients receiving biologic therapy from this specialty pharmacy are enrolled into an RA DTM program, which includes disease-specific education, training, and monitoring aimed to optimize medication adherence. The Modified Health Assessment Questionnaire (HAQ-II) and numerical rating scales (NRS) for pain and fatigue are administered at baseline and every six months thereafter. Measured Outcomes

References
1. Pascual-Ramos V, Contreras-Yanez I, Villa AR, et al. Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability. Arthritis Res Ther. 2009;11(1):R26-36. 2. Haynes R, Ackloo E, Sahota N, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2008, Issue 2. Art. No.: CD000011. 3. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487-97. 4. Grijalva C, Chung C, Arbogast P, et al. Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007;45(10):S66-76. 5. Fernandez-Nebro A, Irigoyen MV, Urena I, et al. Effectiveness, predictive response factors, and safety of anti-tumor necrosis factor (TNF) therapies in anti-TNF-nave rheumatoid arthritis. J Rheumatol. 2007;34(12):2334. 6. Viller F, Guillemin F, Briancon S, et al. Compliance to drug treatment of patients with rheumatoid arthritis: a 3 year longitudinal study. J Rheumatol. 1999;26:2114-22. 7. Clifford S, Barber N, Elliot R, et al. Patient-centered advice is effective in improving adherence to medicines. Pharm World Sci. 2006;28:165-70. 8. Day D. Use of pharmacy claims databases to determine rates of medication adherence. Adv Ther. 2003 May-Jun;20(3):164-76. 9. ten Klooster P, Taal E, van de Laar M. Rasch analysis of the Dutch Health Assessment Questionnaire Disability Index and the Health Assessment Questionnaire II in patients with rheumatoid arthritis. Arthritis and Rheum. 2008;59(12):172128. 10.Wolfe F, Michaud K, Pincus T. Development and validation of the Health Assessment Questionnaire II: a revised version of the health assessment questionnaire. Arthritis and Rheum. 2004;50(10):3296305. 11.Ferraz M, Quaresma M, Aquino L, et al. Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheumatol. 1990;17(8):1022-24. 12.Minnock P, Kirwan J, Bresnihan B. Fatigue is a reliable, sensitive and unique outcome measure in rheumatoid arthritis. Rheumatol. 2009;48:1533-36.

Adherence
Defined as medication possession ratio (MPR) and based on pharmacy refill record Calculated using Standardized Therapy Adherence Research Tool (START,Pfizer)8

HAQ-II
10-item questionnaire with higher scores (ranging 0-3) indicating greater disability9 Reliable and validated in assessing the physical function of patients with RA10

NRS for Pain and Fatigue

11-point (0-10) numerical scales with higher scores indicating worse symptoms Each have demonstrated reliability in assessing pain and fatigue in patients with RA

The correlation between the MPR and the patient-reported measures of disease activity are determined.