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Background: In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing–remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656). Methods: In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course. In the open-label, nonrandomized extensions, patients could receive as-needed additional alemtuzumab or other disease-modifying therapies. Results: Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the CAMMS03409 extension; 33% received a total of 2 alemtuzumab courses, and 73% received no more than 3 courses through Year 12. Over 12 years, annualized relapse rate was 0.09, 71% of patients had stable or improved Expanded Disability Status Scale scores, and 69% were free of 6-month confirmed disability worsening. In Year 12, 73% of patients were free of MRI disease activity. Cumulatively throughout the extensions (Years 7–12), 34% of patients had no evidence of disease activity. Adverse event (AE) incidence declined through Year 12. Infusion-associated reactions peaked at first course and declined thereafter. Cumulative thyroid AE incidence was 50%; one immune thrombocytopenia event occurred, and there were no autoimmune nephropathy cases. Conclusions: Alemtuzumab efficacy was maintained over 12 years in CAMMS223 patients, with 73% receiving no more than three courses. The safety profile in this cohort was consistent with other alemtuzumab clinical trials. [ABSTRACT FROM AUTHOR]

The development of non-specific adverse effects following the administration of an active or inert substance is referred to as nocebo phenomenon. We aimed to estimate the frequency and severity of nocebo responses in clinical trials of pharmacological treatments for neuropathic pain. A systematic Medline search for all randomized, placebo-controlled neuropathic pain trials published between 2000 and 2010 was carried out. Meta-analysis of the frequency of nocebo responses was performed by pooling the percentage of placebo-treated patients that exhibited drug-related adverse events. Nocebo severity was calculated from the percentage of placebo-treated patients that dropped out due to drug-related adverse events. The pooled frequency of nocebo responses in neuropathic pain trials was 52.0% (95% CI: 35.7-67.9) and the pooled nocebo severity was 6.0% (95% CI: 4.5-8.0). Meta-regression analysis revealed an association between the frequency of nocebo responses and the percentage of females in the placebo-treated group ( p = 0.0028). Furthermore, nocebo severity displayed a significant association with the study population ( p = 0.0386). Our data indicates a powerful nocebo effect in neuropathic pain trials that may be influenced by gender- and population-related factors. A strong nocebo effect may be adversely affecting adherence and efficacy of current treatments for neuropathic pain in clinical practice. [ABSTRACT FROM AUTHOR]