Background

Multiple sclerosis (MS) treatment has shifted away from injectable agents, toward oral/infusible disease-modifying therapies (DMTs) that show greater efficacy in reducing disease activity. Clinical benefit has been observed in some patients on these high-efficacy DMTs, but factors that contribute to the likelihood of benefit are unknown.

Objectives

To assess the impact of patient demographics, MS disease characteristics, and brain volumes on likelihood of clinical benefit in patients treated with high-efficacy DMTs, as assessed by patient-reported outcome (PRO) measures.

Methods

This retrospective chart review included adults with MS who completed 2 Patient-Determined Disease Steps (PDDS) measures and at least 2/10 Neurology Quality of Life (NeuroQOL) Short Form scales across 2 time points ≥10 months apart, taking a high-efficacy DMT at baseline. Qualifying DMTs included fingolimod, dimethyl fumarate, natalizumab, rituximab, and ocrelizumab. We examined the influence of various demographics, disease characteristics, and normalized brain volumes on likelihood of clinical benefit. PRO measures included the PDDS and 10 NeuroQOL domains. Patients were grouped as Clinical Benefit vs. Clinical Worsening by change in PDDS score over time (clinically significant change = +/- 1 point). Clinical Benefit was defined as No Change or Improvement on PDDS. Influence of NeuroQOL baseline and change scores was also investigated. NeuroQuant MRI reports provided volumetric data. Statistical analyses used Spearman correlations and logistic regression.

Results

314 patients met inclusion criteria. Factors significantly predicting likelihood of clinical benefit included smoking history (Current v. Former: Odds Ratio (OR)=1.251, CI 5, 95=0.520, 3.008; Current v. Never: OR=2.332, CI 5, 95=1.017, 5.350; Former v. Never: OR=1.864, CI 5, 95=1.070, 3.249; p=.029), body mass index (Odds Ratio (OR)=1.049; CI 5, 95=1.009, 1.089; p=.015), and number of clinical relapses within the study period (OR=1.638; CI 5, 95=1.071, 2.505; p=.023). NeuroQOL scores significantly influencing likelihood of clinical benefit included baseline Fatigue (OR=1.043; CI 5, 95=1.014, 1.073; p=0.004), Sleep Disturbance (OR=1.045; CI 5, 95=1.014, 1.076; p=0.004), and Emotional and Behavioral Dyscontrol (OR=1.030; CI 5, 95=1.002, 1.058; p=0.033); and Social Participation change score (OR=0.918; CI 5, 95=0.876, 0.962; p<0.001).

Conclusions

Patient demographic and disease characteristics appear to better predict clinical benefit than brain volumes. As better baseline and follow-up functioning in several NeuroQOL domains appears to be associated with clinical benefit, clinicians who actively treat these symptoms may see enhanced patient outcomes.

Background

The management of GI symptoms associated with the initiation of DMF has evolved over time with real world experience. The combined effect of GI management strategies has not been assessed in randomized studies and their overall impact on the incidence of GI symptoms and therapy discontinuation due to GI events is currently unclear.

Objectives

To compare discontinuation rate due to gastrointestinal (GI) symptoms in the first year after initiating dimethyl fumarate (DMF) between an early (post launch) and recent DMF cohort of multiple sclerosis (MS) patients at two MS centers.

Methods

Data were collected through chart reviews at Rocky Mountain MS Center and Providence MS Center. The cutoff for Early versus Recent cohort was April 1, 2014. Chi-square, non-parametric, and t-tests were used to determine differences between the two cohorts. Differences in discontinuation due to a GI event for the two cohorts were compared with a Cox proportional hazards model adjusted for baseline characteristics.

Results

Medical records of 700 patients who initiated DMF between March 2013 and December 2017 were reviewed- 302 were Early and 398 Recent. At baseline, Early patients were older (50.30 vs 48.50, p=0.049), had longer disease duration [11.09 (IQR: 7.88, 16.77) vs 6.72 (4.35, 13.72), p<0.001], more history of GI disease (27.8% vs. 22.1%, p=0.099) but lower percent of seasonal allergy (17.9 vs. 24.4, p=0.048). Discontinuation for any reason was higher in Recent patients (37.4% vs. 22.2%, p<0.001). Discontinuation due to GI symptom were 8.6% in the Early patients and 12.1% in the Recent patients (p=0.178). Females [HR: 2.27 (1.12-4.60)] and patients with a history of GI condition [HR: 2.14, (1.32-3.47)] were more likely to discontinue. No significant associations were found between discontinuation and any GI events or previous exposure to natalizumab or other medications. None of the baseline or patient characteristics were found to be risk factor of GI events except study site.

Conclusions

Overall, the discontinuation rate due to GI symptoms was no different between the Early and Recent patient cohorts. However, the odds of having a GI symptom at the Rocky Mountain site were higher although discontinuation for this site was lower suggesting there may be differences in symptom reporting, data abstraction, and GI mitigation strategies between the two centers. Further research with prospective study design and standard documentation and data abstraction tool are needed.

Support: Biogen