Background

Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies.

Objectives

In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group.

Methods

RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ²).

Results

Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ²=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ²=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ²=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ²=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ²=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p=0.02; τ²=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p=0.02; τ²=1.00).

Conclusions

We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.

Background

Alemtuzumab was approved by EMA in 2013 for active relapsing-remitting multiple sclerosis patients (RRMS). The ideal candidate is an active patient in early phase of disease. iIn real world alemtuzumab is also used when many treatments before have failed. Patients with long-term natalizumab exposure and anti JCV seropositivity who stop natalizumab for the risk of PML are a category of patients for whom no specific therapeutic strategy has been established.

At present, neurologists have may highly active drugs but there are no head to head studies directly comparing the efficacy of alemtuzumab with other efficacious therapies and the decision to chose the most suitable medication depends on different factors, such as the potential side effects. In patients who stop natalizumab alemtuzumab can represent a choice.

Objectives

The aim ot this observational study was to evaluate the efficacy and safety of alemtuzumab when used in patients previously treated with natalizumab.

Methods

This is a multicentric retrospective observational study.

Study population is composed by 50 RRMS patients (18 male and 32 female) with a median EDSS of 2 (range 1-7) from five Italian Multiple Sclerosis Centres who stopped natalizumab treatment after a median number of 22 infusions (range 3-114).

Five out of 50 patients were JCV seronegative and in these patients decision to stop natalizumab was due to radiological activity during natalizumab (2 patients), hypertransaminasemia (2 patients), patient request (1 patient). 45 out of patients were JCV seropositive and for these patients reason for stopping was the risk of PML.

Switch to alemtuzumab was made after a median wash out period of 2 months (range 0,7-5 months).

Patients underwent brain MRI at the end of natalizumab treatment, at 6 and 12 months after alemtuzumab infusion.

Results

Brain MRI at six months after alemtuzumab was available for 48 out of 50 patients and in 43 of them neither signs of disease activity nor new lesions were present; 3 patients showed new lesions and 1 patient had radiological activity. No patient showed clinical activity.

Brin MRI at 12 months after alemtuzumab was available in 46 out of 50 patients and in 42 out of 46 there was no sign of disease activity. In 4 patients brain MRI showed disease activity (1 pt) or new lesions (2 pts ) or both (1 pt).

Clinical relapse after alemtuzumab therapy occurred in 1 out of 50 patients; this patient underwent the third infusion of drug.

No patient developed PML.

Conclusions

Alemtuzumab started shortly after natalizumab interruption was highly efficacious in controlling disease course, as 87% of patients showed no evidence of clinical and radiological activity one year after treatment starting.

The choice of alemtuzumab use in JCV seropositive patients must take in consideration the necessity to treat a very severe disease and the safety profile of the drug to which switching.