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Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic drugs: a cross-sectional study

  • Observational Research
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Abstract

The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the discriminative ability of the Morisky–Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity [odds ratio (OR) 1.45; 95% CI, 1.03–2.03; p = 0.032] and subcutaneous route (OR 3.70; 95% CI 1.02–13.48; p = 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.

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References

  1. Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388(10055):2023–2038

    Article  CAS  PubMed  Google Scholar 

  2. Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC et al (2016) 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 68(1):1–26

    Article  PubMed  Google Scholar 

  3. Pasma A, van’t Spijker A, Hazes JM, Busschbach JJ, Luime JJ (2013) Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: a systematic review. Semin Arthritis Rheum 43(1):18–28

    Article  PubMed  Google Scholar 

  4. Wong PK (2016) Medication adherence in patients with rheumatoid arthritis: why do patients not take what we prescribe? Rheumatol Int 36(11):1535–1542

    Article  PubMed  Google Scholar 

  5. Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11(1):44–47

    Article  PubMed  Google Scholar 

  6. Blum MA, Koo D, Doshi JA (2011) Measurement and rates of persistence with and adherence to biologics for rheumatoid arthritis: a systematic review. Clin Ther 33(7):901–913

    Article  PubMed  Google Scholar 

  7. van den Bemt BJ, van den Hoogen FH, Benraad B, Hekster YA, van Riel PL, van Lankveld W (2009) Adherence rates and associations with nonadherence in patients with rheumatoid arthritis using disease modifying antirheumatic drugs. J Rheumatol 36(10):2164–2170

    Article  PubMed  Google Scholar 

  8. van den Bemt BJ, Zwikker HE, van den Ende CH (2012) Medication adherence in patients with rheumatoid arthritis: a critical appraisal of the existing literature. Expert Rev Clin Immunol 8(4):337–351

    Article  PubMed  Google Scholar 

  9. Harrold LR, Andrade SE (2009) Medication adherence of patients with selected rheumatic conditions: a systematic review of the literature. Semin Arthritis Rheum 38(5):396–402

    Article  PubMed  Google Scholar 

  10. Krapek K, King K, Warren SS, George KG, Caputo DA, Mihelich K et al (2004) Medication adherence and associated hemoglobin A1c in type 2 diabetes. Ann Pharmacother 38(9):1357–1362

    Article  CAS  PubMed  Google Scholar 

  11. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581

    Article  PubMed  Google Scholar 

  12. Val Jimenez A, Amoros Ballestero G, Martinez Visa P, Fernandez Ferre ML, Leon Sanroma M (1992) Descriptive study of patient compliance in pharmacologic antihypertensive treatment and validation of the Morisky and Green test. Aten Prim 10(5):767–770

    CAS  Google Scholar 

  13. Morisky DE, Green LW, Levine DM (1986) Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 24(1):67–74

    Article  CAS  PubMed  Google Scholar 

  14. Greenfield S, Apolone G, McNeil BJ, Cleary PD (1993) The importance of co-existent disease in the occurrence of postoperative complications and one-year recovery in patients undergoing total hip replacement. Comorbidity and outcomes after hip replacement. Med Care 31(2):141–154

    Article  CAS  PubMed  Google Scholar 

  15. Executive Summary of The Third Report of The (2001) National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285(19):2486–2497

    Article  Google Scholar 

  16. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R et al (2009) Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 52(1):17–30

    Article  CAS  PubMed  Google Scholar 

  17. Hu G, Tuomilehto J, Borodulin K, Jousilahti P (2007) The joint associations of occupational, commuting, and leisure-time physical activity, and the Framingham risk score on the 10-year risk of coronary heart disease. Eur Heart J 28(4):492–498

    Article  PubMed  Google Scholar 

  18. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383

    Article  CAS  PubMed  Google Scholar 

  19. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van Leeuwen LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48

    Article  CAS  PubMed  Google Scholar 

  20. Esteve-Vives J, Batlle-Gualda E, Reig A (1993) Spanish version of the health assessment questionnaire: reliability, validity and transcultural equivalency. Grupo para la Adaptacion del HAQ a la Poblacion Espanola. J Rheumatol 20(12):2116–2122

    CAS  PubMed  Google Scholar 

  21. Park DC, Hertzog C, Leventhal H, Morrell RW, Leventhal E, Birchmore D et al (1999) Medication adherence in rheumatoid arthritis patients: older is wiser. J Am Geriatr Soc 47(2):172–183

    Article  CAS  PubMed  Google Scholar 

  22. Xia Y, Yin R, Fu T, Zhang L, Zhang Q, Guo G et al (2016) Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis. Patient Prefer Adher 10:735–742

    Google Scholar 

  23. van den Bemt BJ, van Lankveld WG (2007) How can we improve adherence to therapy by patients with rheumatoid arthritis? Nat Clin Pract Rheumatol 3:681 (United States)

    Article  PubMed  Google Scholar 

  24. Koncz T, Pentek M, Brodszky V, Ersek K, Orlewska E, Gulacsi L (2010) Adherence to biologic DMARD therapies in rheumatoid arthritis. Expert Opin Biol Ther 10(9):1367–1378

    Article  CAS  PubMed  Google Scholar 

  25. Salt E, Frazier SK (2010) Adherence to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a narrative review of the literature. Orthop Nurs 29(4):260–275

    Article  PubMed  PubMed Central  Google Scholar 

  26. Harley CR, Frytak JR, Tandon N (2003) Treatment compliance and dosage administration among rheumatoid arthritis patients receiving infliximab, etanercept, or methotrexate. Am J Manag Care. 9(6 Suppl):S136–S143

    PubMed  Google Scholar 

  27. Li P, Blum MA, Von Feldt J, Hennessy S, Doshi JA (2010) Adherence, discontinuation, and switching of biologic therapies in medicaid enrollees with rheumatoid arthritis. Value Health 13(6):805–812

    Article  CAS  PubMed  Google Scholar 

  28. Chernew M, Gibson TB, Yu-Isenberg K, Sokol MC, Rosen AB, Fendrick AM (2008) Effects of increased patient cost sharing on socioeconomic disparities in health care. J Gen Intern Med 23(8):1131–1136

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cannon GW, Mikuls TR, Hayden CL, Ying J, Curtis JR, Reimold AM et al (2011) Merging veterans affairs rheumatoid arthritis registry and pharmacy data to assess methotrexate adherence and disease activity in clinical practice. Arthritis Care Res (Hoboken) 63(12):1680–1690

    Article  Google Scholar 

  30. Grijalva CG, Chung CP, Arbogast PG, Stein CM, Mitchel EF Jr., Griffin MR (2007) Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care 45(10 Supl 2):S66–S76

    Article  PubMed  Google Scholar 

  31. de Thurah A, Norgaard M, Harder I, Stengaard-Pedersen K (2010) Compliance with methotrexate treatment in patients with rheumatoid arthritis: influence of patients’ beliefs about the medicine. A prospective cohort study. Rheumatol Int 30(11):1441–1448

    Article  CAS  PubMed  Google Scholar 

  32. Deyo RA, Inui TS, Sullivan B (1981) Noncompliance with arthritis drugs: magnitude, correlates, and clinical implications. J Rheumatol 8(6):931–936

    CAS  PubMed  Google Scholar 

  33. Sauer BC, Teng CC, Tang D, Leng J, Curtis JR, Mikuls TR et al (2017) Persistence with conventional triple therapy versus a tumor necrosis factor inhibitor and methotrexate in US veterans with rheumatoid arthritis. Arthritis Care Res (Hoboken) 69(3):313–322

    Article  CAS  Google Scholar 

  34. Agarwal S, Zaman T, Handa R (2009) Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. Singapore Med J 50(7):686–692

    CAS  PubMed  Google Scholar 

  35. Hoekstra M et al (2006) Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic study in patients with rheumatoid arthritis. J Rheumatol 33(3):481–485

    CAS  PubMed  Google Scholar 

  36. Hope HF, Bluett J, Barton A, Hyrich KL, Cordingley L, Verstappen SMM (2016) Psychological factors predict adherence to methotrexate in rheumatoid arthritis; findings from a systematic review of rates, predictors and associations with patient-reported and clinical outcomes. RMD Open 2(1):e000171

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sandoval LF, Huang KE, Feldman SR (2013) Adherence to ustekinumab in psoriasis patients. J Drugs Dermatol 12(10):1090–1092

    CAS  PubMed  Google Scholar 

  38. Fraenkel L, Bogardus ST, Concato J, Felson DT, Wittink DR (2004) Patient preferences for treatment of rheumatoid arthritis. Ann Rheum Dis 63(11):1372–1378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jarry JL, Coambs RB, De Maio FG, Rattray AH, Balaram R, Russell A (2002) Projected patterns of compliance associated with Remicade (infliximab) and Enbrel (etanercept) [abstract]. J Rheumatol 29:1564

    Google Scholar 

  40. Rueda Gotor J, Blanco Alonso R (2011) Tocilizumab in rheumatoid arthritis. Reumatol Clin 6s3:S29–S32

    Article  PubMed  Google Scholar 

  41. de Thurah A, Norgaard M, Johansen MB, Stengaard-Pedersen K (2010) Methotrexate compliance among patients with rheumatoid arthritis: the influence of disease activity, disease duration, and co-morbidity in a 10-year longitudinal study. Scand J Rheumatol 39(3):197–205

    Article  PubMed  Google Scholar 

  42. Aletaha D, Smolen JS (2002) Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study. J Rheumatol 29(8):1631–1638

    CAS  PubMed  Google Scholar 

  43. Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I et al (2002) Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. Aids 16(4):605–613

    Article  PubMed  Google Scholar 

  44. Thompson K, Kulkarni J, Sergejew AA (2000) Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr Res 42(3):241–247

    Article  CAS  PubMed  Google Scholar 

  45. Chang MC, Chang YC, Chiou JF, Tsou TS, Lin CC (2002) Overcoming patient-related barriers to cancer pain management for home care patients. A pilot study. Cancer Nurs 25(6):470–476

    Article  PubMed  Google Scholar 

  46. Turbi C, Herrero-Beaumont G, Acebes JC, Torrijos A, Grana J, Miguelez R et al (2004) Compliance and satisfaction with raloxifene versus alendronate for the treatment of postmenopausal osteoporosis in clinical practice: an open-label, prospective, nonrandomized, observational study. Clin Ther 26(2):245–256

    Article  CAS  PubMed  Google Scholar 

  47. Davis NJ, Billett HH, Cohen HW, Arnsten JH (2005) Impact of adherence, knowledge, and quality of life on anticoagulation control. Ann Pharmacother 39(4):632–636

    Article  PubMed  Google Scholar 

  48. Pineiro F, Gil V, Donis M, Orozco D, Torres MT, Merino J (1997) The validity of 6 indirect methods for assessing compliance with pharmacological treatment in dyslipidemias. Aten Prim 19(9):465–468

    CAS  Google Scholar 

  49. Sokka T, Kautiainen H, Pincus T, Toloza S, da Rocha Castelar Pinheiro G G, Lazovskis J et al (2009) Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database. Ann Rheum Dis 68(11):1666–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Putrik P, Ramiro S, Kvien TK, Sokka T, Pavlova M, Uhlig T et al (2014) Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 73(1):198–206

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Olga Pérez (from the FIMABIS) for her statistical advice. This research was supported by FIMABIS.

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Correspondence to Antonio Fernandez-Nebro.

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Natalia Mena-Vazquez has received a speaker honorarium from company MSD and ROCHE. Sara Manrique-Arija has received a speaker honorarium from company MSD, Pfizer and Abbvie. Lucía Yunquera-Romero declares that she has no conflict of interest. Inmaculada Ureña-Garnica declares that she has no conflict of interest. Dr Marta Rojas-Gimenez has received a speaker honorarium from company MSD. Carla Domic has received a speaker honorarium from company MSD. Francisco Gabriel Jimenez-Nuñez has received a speaker honorarium from company MSD, Pfizer and Abbvie. Antonio Fernandez-Nebro has received a speaker honorarium from company MSD, ROCHE and Pfizer.

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Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud (FIMABIS). There were no financial support or other benefits from commercial sources for the work reported on in the manuscript, or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.

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Mena-Vazquez, N., Manrique-Arija, S., Yunquera-Romero, L. et al. Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic drugs: a cross-sectional study. Rheumatol Int 37, 1709–1718 (2017). https://doi.org/10.1007/s00296-017-3758-6

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