Journal of Neurology

, Volume 258, Issue 3, pp 402–411 | Cite as

A multicenter study of the predictors of adherence to self-injected glatiramer acetate for treatment of relapsing-remitting multiple sclerosis

  • Howard Zwibel
  • Gabriel Pardo
  • Shelly Smith
  • Douglas Denney
  • MerriKay Oleen-Burkey
Original Communication


Treatment with disease-modifying immunomodulators is recommended for patients with relapsing-remitting MS (RRMS). However, continuous adherence to treatment with these injected therapies can be challenging. The main objective was to examine the predictors of adherence to glatiramer acetate using a study model derived from Prochaska’s transtheoretical model of change. We conducted a 12-week, prospective, observational study. Potential predictors included readiness stage, MS self-efficacy, decisional balance (pros and cons of self-injection), and injection competence. Adults with RRMS, either treatment-naïve (TN) or treatment-experienced (TE), taking glatiramer acetate for the first time were studied. Interventions (including injection training) were implemented to promote adherence. The evaluable population included 146 TN patients and 88 TE patients who had previously discontinued beta-interferons. Adherence rates did not differ between TN and TE groups (86% for both at week 12); however, predictors of adherence did. For TN patients, greater functional self-efficacy, higher self-injection competence at baseline, and improvement in self-injection competence over the first month of therapy predicted adherence. For TE patients, lower body mass index and longer duration of MS predicted adherence. Interventions to improve self-efficacy and self-injection competence should be a priority when treating TN patients. Behavioral predictors of adherence in TE patients warrant further study.


Adherence Multiple sclerosis Glatiramer acetate Self-injection Readiness Self-efficacy 



We want to acknowledge the entire READY Trial Study Group: James D. Burkholder, MD, Cheryl Ruppenthal, NeuroCare Center, Canton, OH; Robert M. Cain, MD, Laura Sowers, SC, Associated Neurological Specialties, Austin, TX; Martha A. Cline, MD, Neurological Associates, Boise, ID; James S. Cook, MD, Carrie Doub, CRC, Midwest Neurology, Danville, IN; George H. Dooneief, MD, MPH, Kim Roy, RN, The Neurology Group, Norristown, PA; Howard D. Ehrenfeld, MD, Beverly A Johnson-Finley, CRMA, CRC, Neurology & Headache Specialists, Atlanta, GA; Patricia A. Fodor, MD, Christen Kutz, MS, PA-C, Colorado Springs Neurological Associates, Colorado Springs, CO; Edward J. Fox, MD, Lori Mayer, RN, MS Clinic of Central Texas, Round Rock, TX; Stuart Fox, MD, Cynthia Gross, SC, Neuroscience Center of Northern NJ, Morristown, NJ; Suzanne K. Gazda, MD, Ceil Price, SC, Neurology Clinic of San Antonio, San Antonio, TX; Matthews W. Gwynn, MD, Melody Morgan, SC; Neurotrials Research, Atlanta, GA; Barry A. Hendin, MD, Lynne E. Flynn, CCRC, Phoenix Neurological Associates, Phoenix, AZ; W. David Honeycutt, MD, Laura Honeycutt, RN, Neurology Associates, Maitland, FL; Bruce L. Hughes, MD, Judy Green, RN, CRC, Ruan Neurology Clinical Research Center, Des Moines, IA: Samuel Hunter, MD, PhD, Janet Brown, FNP, Advanced Neurosciences Institute, Nashville, TN; Pieter Kark, MD, Diane Austin, RN, Neurological Consultations, Syracuse, NY; Michael Kaufman, MD, Priscilla Russo, BSN, Carolinas MS Center, Charlotte, NC; Seth M. Keller, MD, Binnece J. Green, RN, APNC, Neurology Consultants of Burlington County, Medford, NJ; Peter R. Kinkel, MD, Cindy Heitman, RN, Kinkel Neurologic Center, Williamsville, NY; Robert D. Martinez, MD (Deceased), Judy Boe, SC, Lourdes MS Center, Lafayette, LA; Michael Newmark, MD, Jennifer Marvel, SC, Kelsey-Seybold Clinic, Houston, TX; Gabriel Pardo, MD, Sherry Cadenhead, RN, MS Center at Mercy, Oklahoma City, OK; Gareth Parry, MD, Deb Lascewski, RN, University of Minnesota, Minneapolis, MN; Allan Perel, MD, Diane Lee, RN, Alpha Neurology, Staten Island, NY; Richard A. Sater, MD, PhD, Pamela Sater, SC, High Point Neurological Associates, High Point, NC; Christopher Sheppard, MD, Patricia Blake, RN, Oak Clinic for MS, Uniontown, OH; Dee Silver, MD, Sonia Casillas, CRC, Coastal Neurological Medical Group, La Jolla, CA; James P. Simsarian, MD, Carol Saunders, RN, Neurology Center of Fairfax, Fairfax, VA; Shelly Porter Smith, ANP, Sharon Goss, SC, Neurological Associates, Richmond, VA; Michael R. Stein, MD, Gina A. Paderon, CCRC, Neurological Research Institute of the East Bay, Walnut Creek, CA; Anthony P. Turel, Jr., MD, Jamie Lewson, CRC, Geisinger Medical Center, Danville, PA; Howard Zwibel, MD, Helen Ortega, RN, Neurologic Center of South Florida, Miami, FL; Douglas Denney, PhD, Statistical Consultant, University of Kansas, Lawrence, KS; MerriKay Oleen-Burkey, PhD, Team Leader, and Lillian Pardo, MD, Medical Director, Teva Neuroscience, Kansas City, MO, and the Data Management Center: Phase 4 Health, Toronto, Ontario, Canada. Debbie Due, PhD, NeuroScribe Medical Writing, LLC, contributed to the development of this paper. The study was funded by Teva Neuroscience.


  1. 1.
    Medical Advisory Board of the National Multiple Sclerosis Society (2005) Disease management consensus statement—treatment recommendations for physicians. US Neurology Review. Touch Briefings, London, pp 47–50Google Scholar
  2. 2.
    Perkins DO (2002) Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry 63:1121–1128PubMedGoogle Scholar
  3. 3.
    Ammassari A, Trotta MP, Murri R, Castelli F, Narciso P, Noto P et al (2002) Correlates and predictors of adherence to highly active antiretroviral therapy: overview of published literature. J Acquir Immune Defic Syndr 31(Suppl3):S123–S127PubMedGoogle Scholar
  4. 4.
    Krueger KP, Berger BA, Felkey B (2005) Medication adherence and persistence: a comprehensive review. Adv Ther 22:313–356PubMedCrossRefGoogle Scholar
  5. 5.
    Cunningham A, Gottberg K, von Koch L, Hillert J (2009) Non-adherence to interferon-beta therapy in Swedish patients with multiple sclerosis. Acta Neurol Scand 121:154–160. doi: 10.1111/j.1600-0404.2009 CrossRefGoogle Scholar
  6. 6.
    Twork S, Nippert I, Schere P, Haas J, Pohlau D, Kugler J (2007) Immunomodulating drugs in multiple sclerosis: compliance, satisfaction and adverse effects evaluation in a German multiple sclerosis population. Curr Med Res Opin 23:1209–1215. doi: 10.1185/030079907X188125 PubMedCrossRefGoogle Scholar
  7. 7.
    Loghman-Adham M (2003) Medication noncompliance in patients with chronic disease: issues in dialysis and renal transplantation. Am J Manag Care 9:155–171PubMedGoogle Scholar
  8. 8.
    Lopez-Sanroman A, Bermejo F (2006) Review article: how to control and improve adherence to therapy in inflammatory bowel disease. Aliment Pharmacol Ther 24(Suppl3):45–49PubMedCrossRefGoogle Scholar
  9. 9.
    Chia LR, Schlenk EA, Dunbar-Jacob J (2006) Effect of personal and cultural beliefs on medication adherence in the elderly. Drugs Aging 23:191–202PubMedCrossRefGoogle Scholar
  10. 10.
    Fraser C, Morgante L, Hadjimichael O, Vollmer T (2004) A prospective study of adherence to glatiramer acetate in individuals with multiple sclerosis. J Neurosci Nurs 36:120–129PubMedCrossRefGoogle Scholar
  11. 11.
    DiMatteo MR, Lepper HS, Croghan TW (2000) Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 160:2101–2107PubMedCrossRefGoogle Scholar
  12. 12.
    Bruce JM, Hancock LM, Arnett P, Lynch S (2010) Treatment adherence in multiple sclerosis: association with emotional status, personality, and cognition. J Behav Med 33(3):219–227. doi: 10.1007/s10865-010-9247-y PubMedCrossRefGoogle Scholar
  13. 13.
    Mohr DC, Boudewyn AC, Likosky W, Levine E, Goodkin DE (2001) Injectable medication for the treatment of multiple sclerosis: the influence of self-efficacy expectations and injection anxiety on adherence and ability to self-inject. Ann Behav Med 23:125–132PubMedCrossRefGoogle Scholar
  14. 14.
    Turner AP, Williams RM, Sloan AP, Haselkorn JK (2009) Injection anxiety remains a long-term barrier to medication adherence in multiple sclerosis. Rehabil Psychol 54:116–121. doi: 10.1037/a0014460 PubMedCrossRefGoogle Scholar
  15. 15.
    Holland N, Wiesel P, Cavallo P, Edwards C, Halper J, Kalb R et al (2001) Adherence to disease-modifying therapy in multiple sclerosis: Part I. Rehabil Nurs 26:172–176PubMedGoogle Scholar
  16. 16.
    Tremlett HL, Oger J (2003) Interrupted therapy: stopping and switching of the beta-interferons prescribed for MS. Neurology 61:551–554PubMedGoogle Scholar
  17. 17.
    O’Rourke KE, Hutchinson M (2005) Stopping beta-interferon therapy in multiple sclerosis: an analysis of stopping patterns. Mult Scler 11:46–50PubMedCrossRefGoogle Scholar
  18. 18.
    Steinberg SC, Faris RJ, Chang CF, Chan A, Tankersley MA (2010) Impact of adherence to interferons in the treatment of multiple sclerosis. Clin Drug Investig 30:89–100. doi: 1173-2563/10/0002-0089/$49.95/0 PubMedCrossRefGoogle Scholar
  19. 19.
    Prochaska JO, DiClemente CC (1983) Stages and processes of self-change of smoking: toward an integrative model of change. J Consult Clin Psychol 51:390–395PubMedCrossRefGoogle Scholar
  20. 20.
    Prochaska JO, Velicer WF (1997) The transtheoretical model of health behavior change. Am J Health Promot 12:38–48PubMedGoogle Scholar
  21. 21.
    Prochaska JO, Velicer WF, Rossi JS, Goldstein MG, Marcus BH, Rakowski W et al (1994) Stages of change and decisional balance for 12 problem behaviors. Health Psychol 13:39–46PubMedCrossRefGoogle Scholar
  22. 22.
    Kallings LV, Leijon ME, Kowlski J, Hellenius ML, Stahle A (2009) Self-reported adherence: a method for evaluating prescribed physical activity in primary health care patients. J Phys Act Health 6:483–492PubMedGoogle Scholar
  23. 23.
    Holland N, Wiesel P, Cavallo P, Edwards C, Halper J, Kalb R et al (2001) Adherence to disease-modifying therapy in multiple sclerosis: Part II. Rehabil Nurs 26:221–226PubMedGoogle Scholar
  24. 24.
    Fraser C, Hadjimichael O, Vollmer T (2001) Predictors of adherence to Copaxone therapy in individuals with relapsing-remitting multiple sclerosis. J Neurosci Nurs 33:231–239PubMedCrossRefGoogle Scholar
  25. 25.
    Schwartz CE, Coulthard-Morris L, Zeng Q, Retzlaff P (1996) Measuring self-efficacy in people with multiple sclerosis: a validation study. Arch Phys Med Rehabil 77:394–398PubMedCrossRefGoogle Scholar
  26. 26.
    Lee R, Taira DA (2005) Adherence to oral hypoglycemic agents in Hawaii. Prev Chronic Dis 2:A09PubMedGoogle Scholar
  27. 27.
    Viller F, Guillemin F, Briancon S, Moum T, Suurmeijer T, van den Heuvel W (1999) Compliance to drug treatment of patients with rheumatoid arthritis: a 3 year longitudinal study. J Rheumatol 26:2114–2122PubMedGoogle Scholar
  28. 28.
    Rio J, Porcel J, Tellez N, Sanchez-Betancourt A, Tintore M, Arevalo MJ et al (2005) Factors related with treatment adherence to interferon beta and glatiramer acetate therapy in multiple sclerosis. Mult Scler 11:306–309PubMedCrossRefGoogle Scholar
  29. 29.
    Fraser C, Hadjimichael O, Vollmer T (2003) Predictors of adherence to glatiramer acetate therapy in individuals with self-reported progressive forms of multiple sclerosis. J Neurosci Nurs 35:163–170PubMedCrossRefGoogle Scholar
  30. 30.
    Bruce JM, Hancock LM, Lynch SG (2010) Objective adherence monitoring in multiple sclerosis: initial validation and association with self-report. Mult Scler 16:112–120PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Howard Zwibel
    • 1
  • Gabriel Pardo
    • 2
  • Shelly Smith
    • 3
  • Douglas Denney
    • 4
  • MerriKay Oleen-Burkey
    • 5
  1. 1.Neuroscience ConsultantsComprehensive Multiple Sclerosis CenterCoral GablesUSA
  2. 2.MS Center of OklahomaNeuroScience Institute at MercyOklahoma CityUSA
  3. 3.Commonwealth Pain Specialists (formerly with Neurological Associates, Inc.)RichmondUSA
  4. 4.Department of PsychologyUniversity of KansasLawrenceUSA
  5. 5.Teva Pharmaceuticals, Medical AffairsKansas CityUSA

Personalised recommendations