gms | German Medical Science

22. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie (GAA)

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie

03.12. - 04.12.2015, Dresden

Adherence to Disease Modifying Drugs among Patients with Multiple Sclerosis in Germany: A Retrospective Cohort Study

Meeting Abstract

  • corresponding author presenting/speaker Kerstin Hansen - Allgemeinmedizin/Gesundheitswissenschaften TU Dresden, Dresden, Germany
  • Katrin Schuessel - DAPI, Berlin, Germany
  • Marita Kieble - DAPI, Berlin, Germany
  • Johanna Werning - DAPI, Berlin, Germany
  • Martin Schulz - DAPI, Berlin, Germany
  • Robert Friis - California State University, Long Beach, USA
  • Dieter Poehlau - Kamillus Klinik, Asbach, Germany
  • Norbert Schmitz - McGill University, Montreal, Canada
  • Joachim Kugler - Gesundheitswissenschaften/ Public Health, Dresden, Germany

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie e.V. (GAA). 22. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie. Dresden, 03.-04.12.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15gaa02

doi: 10.3205/15gaa02, urn:nbn:de:0183-15gaa022

Veröffentlicht: 9. Dezember 2015

© 2015 Hansen et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe




Multiple sclerosis (MS) is an inflammatory, chronic, and degenerative autoimmune disease of the central nervous system that, at present, cannot be cured. Approximately 140,000 Germans suffer from MS. Since 2001 four disease modifying-drugs (DMDs), have been approved in Germany: interferon (INF) beta-1ai.m. (Avonex®), interferon (INF) beta-1a s.c. (Rebif®), interferonbeta-1b s.c. (Betaferon®), and glatiramer acetate s.c. (Copaxone®). DMT produce costs of approximately 1,500€/month /person. Guidelines of neurologist experts recommend a treatment over a minimum of two years to gain benefit. We analysed adherence, available co-variates as determinants of adherence and premedication and there influence on adherence.

Materials and Methods

Database: The DAPI data base (the data base of “Deutsches Arzneiprüfungsinstitut e.V.”) contains pharmacy claims data of patients insured by the statutory health insurance system from more than 80% of German community pharmacies (56.16 million patients). The DAPI database contains a complete inventory of German medical products and include information on pharmaceutical ingredients, strength, form of administration, the date of prescription, the medical specialist group, the region, and the insurance status of the patient.

Cohort Definition: Incident users of DMDs were identified with their first (=index) prescription of any DMD during the period between January 01, 2002, and December 31, 2006. There was a 12 months pre-observation period, followed by a 24 months observation period and a 12 months follow-up period.

Measuring adherence: We analysed adherence by two indirect measurement methods concerning the definitions of Cramer et al.: the medication possession ratio (MPR) as proxy for compliance and persistence by determining whether there was a termination of treatment or a defined gap in a patient´s medication profile.

Compliance/ Medication Possession Ratio (MPR): In general, the MPR is calculated from the number of doses dispensed in relation to the dispensing period of time reported as percentages. In our study the denominator represented the observation period, which was a fixed duration defined as 730 days (24 months). The numerator consisted of the number of days in which the patient was covered by a prescribed DMD medication.

Persistence: We measured persistence as the number of days from DMD initiation (index date) to the occurrence of a first gap of more than one-fold duration of medication supply of the previous prescription in the medication profile.

Statistical analyses: For compliance mean (+-standard deviation), median MPR and proportions of therapy cycles during which a patient was compliant were calculated. Not normally distributed MPRs were analysed by Kruskal- Wallis- test, the median MPRs by U-Mann- Whitney. Persistence probabilities were visualized using Kaplan-Meier curves. The association between premedication and non-adherence to DMDs was analysed using the logistic- respectively COX- regression model. All statistical analyses were performed using SPSS.


Patient characteristics: A total of 52,516 medication profiles from 50,057 patients were included in the analyses. The study cohort may be described as follows: 22.6% had a prescription of Avonex®, 28% Betaferon®, 23.5% Copaxone® and 27.1% Rebif®. DMDs were prescribed by neurologists (81.8%), by general practitioners (10%), institutions (5.0%), others (3.9%). The prescriptions came from following regions: from the western part 80.8%, from the east 12.1% and from independent cities (Hamburg, Bremen, Berlin) 7.8%. The distribution over the index years was 18.0% in 2002, 19.3% in 2003, 19.3% in 2004, 22.2% in 2005, 21.2% in 2006. The mean number of premedication (measured as ATC codes) was 8.32 (±8.30).

Compliance/Medication Possession ratio: The distribution of MPRs shows two peaks, one close to zero and one close to one. The median of all MPRs was 0.624. Hence, for half of the profiles patients received medication supplies for less than 62.4% of the follow-up period. The median MPRs for the four study groups were as follows: Avonex® 0.664 Betaferon® 0.644, Rebif® 0.617 and Copaxone® 0.576. We dichotomized the MPRs by defining MPRs≥0.8 as compliant and MPRs < 0.8 as non-compliant. The proportion of medication profiles with a MPR≥0.8 among all DMDs was 39.9%. The respective proportions for the four DMD groups were: Avonex® 42.8%, Betaferon® 40.6%, Rebif® 39.2%, and Copaxone® 37%.

Persistence: Over the entire observation period of 24 months, for a total of 32.3% of all included medication profiles patients were considered persistent. Results for the four DMD groups were: Avonex® 34.2%, Betaferon® 33.4%, Rebif® 31.7%, and Copaxone® 29.8%. We found that 25% of the initiated therapies cycles were interrupted within 86 days and 50% within 312 days. For 22.6% of all therapy cycles the patient did not receive a second prescription within 180 days after index prescription.

Determinants to Adherence: The available co-variates had no clinical relevant influence on adherence.

Premedication and adherence: Within 12 months before starting therapy with DMDs, 85.4% of the MS- patients received at least one physician-prescribed drug. The most common drugs were painkillers (56.8%), anti- hypertensives (36.9%), glucocorticoids (33.3%), anti- ulcerants (31.1%), thyroid disease medications (23.3%), and antidepressants (21.9%).

Adherence to DMDs was significantly higher in patients with premedication with glucocorticoids (OR 1.37; CI(99%): 1.30-1.45), painkillers (OR: 1.16; CI(99%): 1,10-1,22) or anti- ulcerants (OR 1.10; CI(99%): 1.05-1.15), whereas it was significantly lower in patients getting muscle relaxants (OR:0.91; CI(99%):0.86-0.99) or respiratory disease medications (OR:0.92; CI(99%): 0.87-0.99). No association could be seen between antidepressant use and non-adherence to DMDs.


This study shows that less than 40% of the patients were compliant and only 32.3% of the patients were persistent. A quarter of the cohort had already discontinued DMD therapy after 86 days. These results are comparable with other studies. Remarkably, all four DMDs are equally distributed even though three of them are interferons and one is glatiramer acetate. A50/50 distribution may be expected. Between 2002 and 2006, there was an overall increase of index prescriptions from 9,458 to 11,128. The three interferons emerged on the German market in 1998, respectively 1999 ans2001. It usually takes time to implement new therapies. It appears less likely that prevalence of MS has increased in such a short time period. Premedication had a low impact on adherence to DMDs (Nagelkerke R-Square=0.015). Our results indicate that a history of antidepressant prescriptions is not a contraindication for starting therapy with DMDs in MS.