Clinical relevance of thymic and bone marrow outputs in multiple sclerosis patients treated with alemtuzumab.

Thymic and bone marrow outputs were evaluated in 13 sequential samples of 68 multiple sclerosis patients who initiated alemtuzumab and were clinically followed for 48 months. Three months after alemtuzumab infusions, the levels of new T lymphocytes were significantly reduced, but progressively increased reaching the highest values at 36 months, indicating the remarkable capacity of thymic function recovery. Newly produced B cells exceeded baseline levels as early as 3 months after alemtuzumab initiation. Heterogeneous patterns of new T- and B-cell recovery were identified, but without associations with age, sex, previous therapies, development of secondary autoimmunity or infections, and disease re-emergence. Trial registration version 2.0-27/01/2016.

Cladribine vs other drugs in MS: Merging randomized trial with real-life data.

OBJECTIVE: Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data. METHODS: Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity. RESULTS: All weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis. CONCLUSION: In patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study.

In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.

Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job): definition of the cut-off score.

Multiple Sclerosis (MS) mainly affects people of working age. The Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job) was designed to measure difficulties in work-related tasks. Our aim is to define cut-off score of MSQ-Job to identify potential critical situations that might require specific attention. A sample of patients with MS completed the MSQ-Job, WHODAS 2.0 and MSQOL-54 respectively for work difficulties, disability and health-related quality of life (HRQoL) evaluation. K-means Cluster Analysis was used to divide the sample in three groups on the basis of HRQoL and disability. ANOVA test was performed to compare the response pattern between these groups. The cut-off score was defined using the receiver operating characteristic (ROC) curve analyses for MSQ-Job total and count of MSQ-Job items scores ≥3: a score value corresponding to the maximum of the sensitivity-to-specificity ratio was chosen as the cut-off. Out of 180 patients enrolled, twenty were clustered in the higher severity group. The area under the ROC curve was 0.845 for the MSQ-Job total and 0.859 for the count of MSQ-Job items scores ≥3 while the cut-off score was 15.8 for MSQ-Job total and 8 for count of items scored ≥3. We recommend the use of MSQ-Job with this calculation as cut-off for identifying critical situations, e.g. in vocational rehabilitation services, where work-related difficulties have a significant impact in terms of lower quality of life and higher disability.