Characteristics of the included studies.

<p>RTX = Rituximab, PLC = Placebo.</p>*<p>Blinding of the patients was questionable due to adverse events.</p

Rituximab in Relapsing and Progressive Forms of Multiple Sclerosis: A Systematic Review

<div><p>Background</p><p>Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS.</p><p>Objectives</p><p>To evaluate the efficacy and safety of rituximab for MS treatment.</p><p>Data collection</p><p>Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies.</p><p>Main results</p><p>Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events.</p><p>Author’s conclusion</p><p>Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.</p></div

Flow chart with information on the identified and excluded articles.

<p>Flow chart with information on the identified and excluded articles.</p

Fetal Characteristics at Birth.

<p>S.D. = standard deviation.</p

Maternal Laboratory Values^*.

<p>*based on maximum value recorded.</p><p>U = units, L = liter, mg = milligram, dL = deciliter, µmol = micromole.</p

Predictors of Fetal Complications.

<p>Predictors of Fetal Complications.</p

Maternal Demographics.

<p>S.D. = standard deviation, BMI = body mass index.</p

Representative extracted ion chromatogram of INH in small hair samples from a patient on INH (A) and a patient not taking INH (B).

<p>Representative extracted ion chromatogram of INH in small hair samples from a patient on INH (A) and a patient not taking INH (B).</p

Validation of method accuracy, precision and recovery for the analysis of isoniazid in small hair samples.

<p>Validation of method accuracy, precision and recovery for the analysis of isoniazid in small hair samples.</p

INH concentrations in 18 hair samples from patients recruited from the San Francisco Department of Public Health TB Clinic (11 with active TB; 7 with latent TB).

<p>INH concentrations in 18 hair samples from patients recruited from the San Francisco Department of Public Health TB Clinic (11 with active TB; 7 with latent TB).</p