Almirall Hermal GmbH

Cognitive impairment is a common manifestation of multiple sclerosis (MS).

To assess by systematic review and meta-analysis available evidence regarding the impact of nabiximols oromucosal spray on cognition in patients with MS.

A systematic literature search of clinical studies (all types, any comparator) that measured cognitive function in patients with MS spasticity treated with nabiximols. Meta-analysis for cognitive endpoints was not possible due to heterogenous measurement instruments and outcomes. Meta-analysis was performed for adverse events (AEs) of special interest (cognition disorders) reported in randomized controlled trials (RCTs) of nabiximols versus placebo in patients with MS (with or without spasticity). Certainty of evidence and risk of bias were assessed.

Seven clinical studies (three RCTs) directly assessing cognitive function were included in the qualitative analysis. There was no consistent evidence to suggest that nabiximols causes cognitive impairment as assessed by a range of specific psychometric instruments across cognitive domains. Thirteen double-blind, placebo-controlled RCTs (nabiximols, n = 964; placebo, n = 904) were included in the meta-analysis of cognitive AEs. Most cognitive AEs (30 of 32 events, 93.8%) reported with nabiximols in MS patients occurred with not in-label use, i.e., dosage >12 sprays per day and/or not administered primarily for treatment of spasticity.

Within the limitations of the review, we can conclude that no detrimental effects of nabiximols on cognitive function were observed in patients with MS spasticity during up to 12 months follow-up and that cognitive AEs were rare and occurred only when nabiximols was not used according to its approved label.

Fumaric acid esters (FAEs) are a well-established treatment option for long-term therapy of moderate to severe plaque psoriasis. This study examines effectiveness of FAEs for the treatment of plaque psoriasis in real-world practice at 12 months and if patient characteristics affect the odds of clinical response.

A descriptive, multivariable logistic regression analysis was conducted in a cohort drawn from the German registry PsoBest. Baseline patient characteristics were assessed as potential treatment effect modifiers.

444 patients (mean age 47.0 years, 39.0% female) were eligible for response analysis using nonresponder imputation at month 12. Of these, 39.6% achieved clinical response, i.e. Psoriasis Area and Severity Index (PASI) ≤ 3 or skin clearance. In logistic regression analysis (R² = 0.114), only baseline PASI was a significant factor: patients with PASI < 10 had a 4 times higher odds (p ≤ .001, OR 4.088), patients with PASI of 10-20 a twofold higher odds of response (p ≤ .044, OR 1.961) compared to those with PASI > 20. Neither sex, age, body weight, disease duration, comorbidity nor pretreatment had an impact on the odds of response (p > .05).

FAEs showed a favorable response at 12 months, largely independent of patient characteristics.

Dimethylfumarate (DMF) is approved for the treatment of moderate to severe psoriasis. In clinical practice, DMF tolerability is improved by slowly up-titrating the dose. Time-to-onset of gastrointestinal complaints (a common adverse event [AE]) is ∼4 weeks, coinciding with the increase in dose to one 120-mg tablet. The average DMF dose during maintenance treatment is also often lower than the maximum indicated dose of 720 mg/day. Here, a simplified dose-escalation strategy is described, where twice-daily DMF was up-titrated to a maximum of 720 mg/day (if required) in week 7. Ten patients received DMF according to the new scheme (maximum dose: 720 mg/day [n = 5], 480 mg/day [n = 3; escalation halted early due to good efficacy], and ≤240 mg/day [n = 2] by week 12). Mean Psoriasis Area Severity Index (PASI) decreased from 7.2 to 0.9 between weeks 0 and 24. Absolute Psoriasis Area Severity Index (aPASI) was ≤3 for 7 and 6 patients at weeks 12 and 24, respectively. Affected BSA and DLQI demonstrated similar improvements. Treatment was terminated in 3 patients due to AEs (diarrhea and lymphopenia). In this case series, simplified DMF dosing was largely well-tolerated and provided similar efficacy to the current scheme. Higher doses were reached more quickly and the dosing regimen was simpler for patients (twice instead of three times daily).