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

Virginia Pascual-Ramos, Irazú Contreras-Yáñez, Antonio R Villa, Javier Cabiedes, Marina Rull-Gabayet, Virginia Pascual-Ramos, Irazú Contreras-Yáñez, Antonio R Villa, Javier Cabiedes, Marina Rull-Gabayet

Abstract

Introduction: Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators.

Methods: Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used.

Results: The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P < or = 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (> or = 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 +/- 4.6 versus 13.6 +/- 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P < or = 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02).

Conclusions: Discontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.

Figures

Figure 1
Figure 1
Cumulative risk of being persistent on therapy over 2 years of follow-up. Persistence decreased from 98% at visit 2 (2.15 ± 0.44 months of follow-up) to 34% at visit 13 (24.6 ± 6.17 months of follow-up).
Figure 2
Figure 2
Comparison of consecutive 28-joint disease activity scores between persistent patients and nonpersistent patients. Consecutive 28-joint disease activity score (DAS28) for persistent patients (blue bars) and nonpersistent patients (green bars). Thick line in middle of bar, mean DAS28 value; top and bottom of bar, upper and lower quartiles, respectively; top and bottom lines, maximum and minimum values, respectively. x axis, consecutive visits (V); y axis, DAS28 values. *Differences with P ≤ 0.05. SD, standard deviation.
Figure 3
Figure 3
Comparison of consecutive health assessment questionnaire scores between persistent patients and nonpersistent patients. Consecutive health assessment questionnaire (HAQ) scores for persistent patients (blue bars) and nonpersistent patients (green bars). Thick line in middle of bar, mean value; top and bottom of bar, upper and lower quartiles, respectively; top and bottom lines, maximum and minimum values, respectively. x axis, consecutive visits (V); y axis, HAQ values. *Differences with P ≤ 0.05. SD, standard deviation.

References

    1. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481–494. doi: 10.1002/art.1780370408.
    1. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–497. doi: 10.1056/NEJMra050100.
    1. Steiner JF, Earnest MA. The language of medication taking. Ann Intern Med. 2000;132:926–930.
    1. Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK. Medication compliance and persistence terminology and definitions. Value Health. 2008;11:44–47.
    1. Harrold LR, Andrade SE. Medication adherence of patients with selected rheumatic conditions: a systematic review of the literature. Semin Arthritis Rheum. 2008
    1. Walsh JC, Mandalia S, Gazzard BG. Responses to a month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome. AIDS. 2002;16:269–277. doi: 10.1097/00002030-200201250-00017.
    1. Haynes RB, Taylor DW, Sackett DL, Gibson ES, Bernholz CD, Mukherjee J. Can simple clinical measurements detect patient noncompliance? Hypertension. 1980;2:757–764.
    1. Cramer J, Rosenheck R, Kirk G, Krol W, Krystal J. Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes. Value Health. 2003;6:566–573. doi: 10.1046/j.1524-4733.2003.65269.x.
    1. Haynes RB, McDonald HP, Garg AX. Helping patients follow prescribed treatment: clinical applications. JAMA. 2002;288:2880–2883. doi: 10.1001/jama.288.22.2880.
    1. de Klerk E, Heijde D van der, Landewé R, Tempel H van der, Urquhart J, Linden S van der. Patient compliance in rheumatoid arthritis, polymyalgia rheumatica, and gout. J Rheumatol. 2003;30:44–54.
    1. de Klerk E, Heijde D van der, Tempel H van der, Linden S van der. Development of a questionnaire to investigate patient compliance with antirheumatic drug therapy. J Rheumatol. 1999;26:2635–2641.
    1. de Klerk E, Heijde D van der, Tempel H van der, Linden S van der. The Compliance-Questionnaire-Rheumatology compared with electronic medication event monitoring: a validation study. J Rheumatol. 2003;30:2469–2475.
    1. Callahan LF, Brooks RH, Pincus T. Further analysis of learned helplessness in rheumatoid arthritis using a 'Rheumatology Attitudes Index'. J Rheumatol. 1988;15:418–426.
    1. Gossec L, Tubach F, Dougados M, Ravaud P. Reporting of adherence to medication in recent randomized controlled trials of 6 chronic diseases: a systematic literature review. Am J Med Sci. 2007;334:248–254. doi: 10.1097/MAJ.0b013e318068dde8.
    1. Deyo RA, Inui TS, Sullivan B. Noncompliance with arthritis drugs: magnitude, correlates, and clinical implications. J Rheumatol. 1981;8:931–936.
    1. Tuncay R, Eksioglu E, Cakir B, Gurcay E, Cakci A. Factors affecting drug treatment compliance in patients with rheumatoid arthritis. Rheumatol Int. 2007;27:743–746. doi: 10.1007/s00296-006-0299-9.
    1. García-González A, Richardson M, García Popa-Lisseanu M, Cox V, Kallen MA, Janssen N, Ng B, Marcus DM, Reveille JD, Suárez-Almazor ME. Treatment adherence in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol. 2008;27:883–889. doi: 10.1007/s10067-007-0816-6.
    1. Lorish CD, Richards B, Brown S. Missed medication doses in rheumatic arthritis patients: intentional and unintentional reasons. Arthritis Care Res. 1989;2:3–9. doi: 10.1002/anr.1790020103.
    1. Lorish CD, Richards B, Brown S. Perspective of the patient with rheumatoid arthritis on issues related to missed medication. Arthritis Care Res. 1990;3:78–84.
    1. Viller F, Guillemin F, Briançon S, Moum T, Suurmeijer T, Heuvel W van den. Compliance to drug treatment of patients with rheumatoid arthritis: a 3 year longitudinal study. J Rheumatol. 1999;26:2114–2122.
    1. Viller F, Guillemin F, Briançon S, Moum T, Suurmeijer T, Heuvel W van den. Compliance with drug therapy in rheumatoid arthritis. A longitudinal European study. Joint Bone Spine. 2000;67:178–182.
    1. Grijalva CG, Chung CP, Arbogast PG, Stein CM, Mitchel EF, Jr, Griffin MR. Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007;45:S66–S76. doi: 10.1097/01.mlr.0000241107.15133.54.
    1. Curkendall S, Patel V, Gleeson M, Campbell RS, Zagari M, Dubois R. Compliance with biologic therapies for rheumatoid arthritis: do patients out-of-pocket payments matter? Arthritis Rheum. 2008;59:1519–1526. doi: 10.1002/art.24114.
    1. Ramey DR, Raynauld JP, Fries JF. The health assessment questionnaire 1992; status and review. Arthritis Care Res. 1992;5:119–129. doi: 10.1002/art.1790050303.
    1. Prevoo ML, van't Hof MA, Kuper HH, VAN Leeuwen MA, Putte LB van de, van Riel PL. Modified disease activity score that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–48. doi: 10.1002/art.1780380107.
    1. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurement in medical research. BMJ. 1990;300:230–235.
    1. Andrade SE, Kahler KH, Frech F, Chan KA. Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf. 2006;15:565–575. doi: 10.1002/pds.1230.
    1. Peterson AM, Nau DP, Cramer JA, Benner J, Gwadry-Sridhar F, Nichol M. A checklist for medication compliance and persistence studies using retrospective databases. Value Health. 2007;10:3–12. doi: 10.1111/j.1524-4733.2006.00139.x.
    1. Kristensen LE, Saxne T, Nilsson J-A, Geborek P. Impact of concomitant DMARD therapy on adherence to treatment with etarnecept and infliximab in rheumatoid arthritis. Results from a six-year observational study in Southern Sweden. Arthritis Res Ther. 2006;8:R174. doi: 10.1186/ar2084.
    1. Solomon DH, Stedman M, Licari A, Weinblatt ME, Maher N, Shadick N. Agreement between patient report and medical record review for medications used for rheumatoid arthritis: the accuracy of self-reported medication information in patient registries. Arthritis Rheum. 2007;57:234–239. doi: 10.1002/art.22549.
    1. Lee P, Tan LJ. Drug compliance in outpatients with rheumatoid arthritis. Aust N Z J Med. 1979;9:274–277.
    1. Zink A, Listing J, Kary S, Ramlau P, Stoyanova-Scholz M, Babinsky K, von Hinueber U, Gromnica-Ihle E, Wassenberg S, Antoni C, Herzer P, Kekow J, Schneider M, Rau R. Treatment continuation in patients receiving biological agents or conventional DMARD therapy. Ann Rheum Dis. 2005;64:1274–1279. doi: 10.1136/ard.2004.031476.
    1. Lipsky PE, Heijde DM van der, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000;343:1594–1602. doi: 10.1056/NEJM200011303432202.
    1. Hoekstra M, Laar MA van de, Bernelot Moens HJ, Kruijsen MW, Haagsma CJ. Longterm observational study of methotrexate use in a Dutch cohort of 1022 patients with rheumatoid arthritis. J Rheumatol. 2003;30:2325–2329.
    1. Klareskog L, van der HD, de Jager JP, Gough A, Kalden J, Malaise M, Martin Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M. Therapeutic effect of the combination of etarnecept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomized controlled trial. Lancet. 2004;363:675–681. doi: 10.1016/S0140-6736(04)15640-7.
    1. Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW, Kremer J, Bear MB, Rich WJ, McCabe D. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46:614–624. doi: 10.1002/art.10141.
    1. Dougados M, Emery P, Lemmel EM, de la Serna R, Zerbini CA, Brin S, van Riel P. Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6 months data. J Rheumatol. 2003;30:2572–2579.
    1. Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Furst DE, Luggen ME, Keystone E, Weisman MH, Bensen WM, Kaine JL, Ruderman FM, Coleman P, Curtis DL, Kopp EJ, Kantor SM, Waltuck J, Lindsley HB, Markenson JA, Strand V, Crawfor B, Fernando I, Simpson K, Bathon JM. Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002;137:726–733.
    1. Kristensen LE, Saxne T, Geborek P. The LUNDEX, a new index of drug efficacy in clinical practice: results of a five-year observational study of treatment with infliximab and etarnecept among rheumatoid arthritis patients in southern Sweden. Arthritis Rheum. 2006;54:600–606. doi: 10.1002/art.21570.
    1. Stephenson BJ, Rowe BH, Haynes RB, Macharia WM, Leon G. The rational clinical examination. Is this patient taking the treatment as prescribed? . JAMA. 1993;269:2779–2781. doi: 10.1001/jama.269.21.2779.
    1. Elliot WJ. Compliance strategies. Curr Opin Nephrol Hypertens. 1994;3:271–278. doi: 10.1097/00041552-199405000-00007.
    1. Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998;36:1138–1161. doi: 10.1097/00005650-199808000-00004.
    1. Myers LB, Midence K. Concepts and issues in adherence. In: Myers LB, Midence K, editor. Adherence to Treatment in Medical Conditions. Amsterdam: Harwood Academic; 1998. pp. 3–18.
    1. Tarlov AR, Ware JE, Greenfield S, Nelson EC, Perrin E, Zubkokk M. The medical outcomes study. An application of methods for monitoring the results of medical care. JAMA. 1989;262:925–930. doi: 10.1001/jama.262.7.925.
    1. Mody GM, Cardiel MH. Challenges in the management of rheumatoid arthritis in developing countries. Best Pract Res Clin Rheumatol. 2008;22:621–641. doi: 10.1016/j.berh.2008.04.003.
    1. National Committee for Quality Assurance . HEDIS 2006 Technical Specifications: Disease Modifying Anti-rheumatic Drug Therapy in Rheumatoid Arthritis. Washington, DC: National Committee for Quality Assurance; 2005.
    1. Kahn KL, Mclean CH, Wong AL, Rubenstein LZ, Liu H, Fitzpatrick DM, Harker JO, Chen WP, Traina SB, Mittman BS, Hahn BH, Paulus HE. Assessment of American College of Rheumatology quality criteria for rheumatoid arthritis in a pre-quality criteria patient cohort. Arthritis Rheum. 2007;57:707–715. doi: 10.1002/art.22781.

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