Dosing Frequency a Prime Factor in Non Adherence to Disease-modifying Therapy in Patients with Multiple Sclerosis

Nonadherence is highest in patients undergoing treatment with subcutaneous or intramuscular injection formulations of DMT.

Copenhagen, Denmark — October 4, 2013 – Results of a large survey of patients with multiple sclerosis (MS) undergoing disease-modifying therapy (DMT) identified injection frequency, depression, forgetfulness, and alcohol consumption as major factors in non-adherence to treatment. However, more importantly, the findings underscored the urgent need for new treatment options that are more convenient to administer, longer-lasting, and require fewer doses to remember in order to increase compliance with DMT, a crucial element in controlling MS disease progression and symptoms.

Non-adherence rates ranged from 7.5% with IV natalizumab and 64% with subcutaneous glatiramer acetate. Mode and frequency of treatment administration was a major factor in adherence to DMT. The investigators noted that subjects receiving monthly infusion treatment with natalizumab were by far the most compliant to DMT and were 90% less likely to be non-adherent (P<.001).

Findings were presented during the October 4th “Long-term Treatment Monitoring” session of the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the 18th Annual Conference of Rehabilitation in MS. Chiayi Chen RN, PhD, and colleagues from The Providence Brain and Spine Institute, Portland, OR, conducted an observational, cross-sectional study using survey data from participants in the Pacific Northwest multiple sclerosis registry during the year 2012 that aimed to define the prevalence of non-adherence in patients with relapsing MS and identify the factors associated with non-adherence to DMT. Also on-hand to answer questions during the poster session was another member of the team, Stanley Cohan MD, PhD.

This analysis included 994 subjects with relapsing MS who were on an FDA-approved DMT. Of these, 42.6% were determined to be non-adherent, which was defined as missing a dose within the three months prior to survey completion.

Non-adherent subjects tended to be younger, both at the time of survey (51.5 years compared to 53.2 years in adherent subjects; P= 0.01) and at diagnosis (38.5 years versus 39.9 years, respectively; P= 0.03). More non-adherent participants reported depression (35.8% of non-adherent patients compared to 28% of adherent subjects; P= 0.01) as well as more frequent alcohol use compared to the adherent group (39.2% versus 33.3%, respectively; P=0.008).

Non-adherence rates were highest in subjects requiring subcutaneous or intramuscular injectable interferon beta-1a, interferon beta-1b, or glatiramer acetate; rates of non-adherence were 64% for interferon beta-1a subcutaneous, 64% for glatiramer acetate subcutaneous, 61.4% for interferon beta-1b subcutaneous, and 36.4% for IFNB1a intramuscular. The lowest non-adherence rate in the cohort of subjects requiring injections was 7.5% with natalizumab IV. The rates differed significantly (P=0.001) by dosing frequency. Forgetfulness, injection site pain, and side effects were reported by 55.9%, 15.1%, and 14.0% of the non-adherent subjects, respectively, as the top reasons for missing medication.

Forgetfulness was the major reason given for non-adherence to oral medication; 19 (46.3%) subjects taking oral fingolimod were categorized as non-adherent. Among these subjects, 74% cited forgetfulness as the reason for non-adherence to DMT. “This finding surprised us; simple forgetfulness really was the reason. But we must bear in mind that missing a daily dose has less overall impact that missing a twice or three-times weekly dose,” said Chen. Cohan added, “side effects entered into this not at all — fingolimod side effects are negligible.”

In subjects on an injectable DMT regimen, injection frequency was the major determinant of non-adherence, after adjusting for education, alcohol use, age, being diagnosed with depression, and having fatigue symptoms; compared with subjects on a weekly injection schedule subjects needing daily or thrice weekly injections were three times more likely to be non-adherent.

Summing up the results, Chen said “this study validated the high prevalence of non-adherence to DMT in MS patients.” She noted that there was possible study bias from the retrospective design. “What is needed are prospective studies that use a continuous adherence measure to really assess the relationship between medication adherence and long-term clinical outcomes.”

This study was funded by a research grant from Novartis.