Effectiveness of Ocrelizumab in Primary Progressive Multiple Sclerosis: a Multicenter, Retrospective, Real-world Study (OPPORTUNITY).

Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07-3.65; p = 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years.

High-Dose Intravenous Immunoglobulin Is Effective in Painful Diabetic Polyneuropathy Resistant to Conventional Treatments. Results of a Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

OBJECTIVES: The efficacy and safety of high-dose intravenous immunoglobulin (IVIG) in treatment-resistant diabetic painful polyneuropathy (DPN) were assessed. DESIGN: This was a randomized, double-blind, placebo-controlled, multicenter trial (EudraCT 2010-023883-42). SETTING: This trial was conducted at eight sites in Italy with a neurology specialist level of care. SUBJECTS: Twenty-six diabetic patients with DPN who reported baseline severity of pain >60 units (mm) on a VAS scale at enrollment and were resistant to antidepressants and antiepileptic drugs were enrolled; 23 were randomized (11 in the IVIG arm and 12 in the placebo arm). All patients completed the study and were evaluated. All patients were Caucasian, 15 were male, and 21 had a diagnosis of type II diabetes. METHODS: IVIG (0.4 g/kg/d) or placebo was given for five consecutive days. Pain intensity (visual analog scale, Neuropathic Pain Symptom Inventory) and quality of life (36-Item Short-Form Health Survey, Clinical/Patient Global Impression of Change questionnaires) assessments were performed at visits: baseline, start of therapy (one week later), end of therapy (five days later), and follow-up (four and eight weeks later). RESULTS: The study achieved its prespecified primary end point of ≥50% pain reduction at four weeks after IVIG, achieved in seven of 11 patients (63.6%) in the IVIG group vs zero of 12 in the placebo group (P = 0.0013). Only two adverse events were reported during the study: one patient in the treatment arm reported a mild "dermatitis psoriasiform," whereas one patient from the placebo group reported a mild "influenza." CONCLUSIONS: Treatment with IVIG at the dose given was efficacious and safe for patients with DPN resistant to standard therapies.

The Prevalence of Multiple Sclerosis in the Metropolitan Area of Rome: A Capture-Recapture Analysis.

BACKGROUND: Limited data are available on the prevalence of multiple sclerosis (MS) in central Italy. The objective of this study is to estimate MS prevalence in the metropolitan area of Rome. METHODS: We used the capture-recapture method to calculate prevalence estimates in the study area. The selected prevalence day was December 31, 2015. A total of 1,007 patients, with a definite diagnosis of MS according to the revised McDonald's criteria, were considered for crude, age- and sex-specific prevalence estimation. RESULTS: The overall crude prevalence rate was 146.2 cases per 100,000 (95% CI 119.9-172.5). A higher prevalence rate was recorded in females (194.1, 95% CI 149.6-238.6) than in males (93.0, 95% CI 67.2-118.8) with a female to male ratio of 1.8. Age-specific prevalence peaked in the 25-34 , 35-44 and 45-54 years class; moreover, it was found to increase up to the 45-54 years age group in females and the 35-44 years age group in males, decreasing thereafter. CONCLUSION: The results confirm that the metropolitan area of Rome is a high-risk area for MS.