Background

Migraine headache presents simultaneously with early symptoms in most patients with MS, showing association with MS prevalence and incidence, but the pathological significance of headache remains unclear. Self-reporting instruments offer an opportunity to study this relationship.

Objectives

Cross-sectional study of self-reported headache frequency, MS disability, severity, and disease-modifying therapy (DMT) retrospectively using a de‑identified, archival, database from MS Care Connect^TM, a digital application (InterPRO Bioscience).

Methods

Patient survey responses were transformed into number of headache days per month (HD). A generalized linear mixed-effects (GLMM) model was performed to test the association of HD with: sex, age, weight, disease modifying therapy class, patient self-reported history of MS, MS phenotype, DMT, and either Patient-Derived Disability Score (PDDS) or Patient-Derived MS Severity Score (P‑MSSS). Additional post hoc comparisons further tested associations among significant variables.

Results

253 participants self-reported headache (79% CIS/RRMS, 10% PPMS/SPMS, others “unsure”; mean 45.4 y+11.4 SD, median 45.4 y). Of the 219 suffering >1 HD, 78.7% were female and used mainly highly effective IV and oral MS DMTs with a mean 9.0 HD (median 3). Responders self-reported PDDS (mean 2.2+ 2.0 SD) and yearly relapses mean 0.32 ± 0.6 with a calculated, P‑MSSS decile mean 3.67+2.54. No correlations were detected between HD and PDDS or P-MSSS. A small PPMS/SPMS cohort demonstrated higher median PDDS in the high HD group. Daily headache had highest median PDDS and P-MSSS in RRMS phenotype.

A Poisson GLMM revealed significantly lower HD for males, older subjects, and RRMS subjects over females, younger subjects, and progressive MS subjects, respectively. No interaction occurred among these three variables (age, gender, and MS phenotype). However, a skewed frequency distribution of DMT use by males (more likely to be treated) was associated with fewer HD than females; this skewing did not extend to DMT type. Progressive MS patients were less likely to be on any DMT despite having high HD. The model found non-significant contributions of family history of MS, DMT, P-MSSS and weight. When stratifying PDDS and age and comparing high and low HD groups, younger people (<45y) with high HD have lower PDDS than peers with low HD. In contrast, older people (45+y) have more HD with higher PDDS as compared to similarly aged peers with low HD, although this comparison did not reach significance.

Conclusions

A self-efficacy digital tool presented opportunities to study the interaction of migraine and MS. We significantly found that older, CIS/RRMS, or male subjects have fewer HD than younger, PPMS/SPMS, or female subjects, respectively. Age, MS phenotype, and gender predict HD in our best models and must be controlled in future studies; a relationship to PDDS and P-MSSS requires further investigation in a larger cohort.

Background

Alemtuzumab (ALE) achieves effective protection against disability progression and often improvement in patients with severe multiple sclerosis (MS). The SF-36 health survey is a validated quality-of-life (QoL) outcome with multiple subscales, and has shown differences in low disability MS and short duration of disease in ALE trials..

Objectives

Using longitudinal linear multivariate models, assess changes in QoL in groups switching from other therapies to ALE, or undergoing additional therapy with ALE.

Methods

We prospectively measured changes in QoL with open-label ALE treatment using SF-36 in two arms: ALE-experienced (ALE-X) and ALE-naïve (ALE-N) cohorts with relapsing-remitting MS and secondary progressive MS with relapse, expanded disability status scale (EDSS)<7.0. ALE was given per standard protocols. 60 subjects were recruited and 55 completed the entire intent-to-treat prospective study. The SF-36 questionnaire was completed annually. Mean physical and emotional scores (PS, ES) were calculated from the respective subcategories of the SF-36. Longitudinal linear mixed models were used to test for an association between scores and the primary predictors of either total number of ALE treatments or study arm, with age, sex, EDSS, MS phenotype, and age at MS symptom onset as covariates. Study month was used as the random effect in the models.

Results

Differences of PS and ES between baseline and end of study were not significant, likely a preservation of QoL. Regarding absolute scores, MS phenotype was not associated with scores in any model tested. Total number of ALE treatments had no impact on PS, but covariates age and EDSS were significantly associated with PS. As EDSS increases, PS and ES are lower/worse without an effect of sex. Unexpectedly, PS were subtly but significantly with increasing age at ALE treatment and decreasing EDSS (older patients report higherincreased PS); more dramatic differences were seen for ES. ALE-X patients showed marginal significantly higher PS over ALE-N, possibly related to long-term therapy. ALE-X patients reported a significantly higher ES score than their ALE-N peers over the treatment course. ES also significantly increased with increasing ALE treatments (about 2% for each additional ALE treatment). Covariates of age at MS onset, sex, and EDSS were significantly associated with ES. Lower age at onset, females, and higher EDSS were associated with lower ES.

Conclusions

Both experienced and naïve ALE groups have relatively stable long-term QoL measures. As expected, QoL is negatively associated with EDSS. Older patients perceive greater physical health in our cohorts. Shorter disease duration, lower EDSS, males, and receiving greater ALE courses report better emotional health than those with longer disease duration, higher EDSS, females, or patients with fewer treatments, respectively. Greater QoL in experienced patients may reflect long-term benefit and treatment response.