Sandborn and associates (2005) performed 2 controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active CD. In the first study, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8. The primary outcome was response, defined by a decrease in the CDAI score of at least 70 points, at week 10. In the second study, 339 patients who had a response to natalizumab in the first trial were randomly reassigned to receive 300 mg of natalizumab or placebo every 4 weeks through week 56. The primary outcome was a sustained response through week 36. A secondary outcome in both trials was disease remission (a CDAI score of less than 150). The first study showed that the natalizumab and placebo groups had similar rates of response (56 % and 49 %, respectively; p = ) and remission (37 % and 30 %, respectively; p = ) at 10 weeks. Continuing natalizumab in the second study resulted in higher rates of sustained response (61 % versus 28 %, p < ) and remission (44 % versus 26 %, p = ) through week 36 than did switching to placebo. Serious adverse events occurred in 7 % of each group in the first trial and in 10 % of the placebo group and 8 % of the natalizumab group in the second trial. In an open-label extension study, a patient treated with natalizumab died from PML. The authors concluded that induction therapy with natalizumab for CD resulted in small, non-significant improvements in response and remission rates. Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every 4 weeks.
The . Pharmacopoeial Convention has concluded that rituximab is indicated for treatment of Waldenström’s macroglobulinemia. Dimopolous et al (2002) reported on 27 patients with symptomatic Waldenström’s macroglobulinemia who were treated with rituximab. Twelve patients (44 %; 95 % confidence interval [CI]: % to %) achieved a partial response after treatment with rituximab. Median time to response was months (range of to months). The median time to progression for all patients was 16 months, and with a median follow-up of months, 9 of 12 responding patients remain free of progression. The investigators reported that approximately 25 % of patients experienced some mild form of infusion-related toxicity, usually fever and chills.
Medications are modestly effective at decreasing the number of attacks in RRMS and in reducing the accumulation of brain lesions, which is measured using gadolinium - enhanced magnetic resonance imaging (MRI).  Interferons and glatiramer acetate are roughly equivalent, reducing relapses by approximately 30% and their safe profile make them the first-line treatments.  Nevertheless, not all the patients are responsive to these therapies. It is known that 30% of MS patients are non-responsive to Beta interferon.  One of the factors related to non-respondance is the presence of high levels of interferon beta neutralizing antibodies . Interferon therapy, and specially interferon beta-1b, induces the production of neutralizing antibodies, usually in the second 6 months of treatment, in 5 to 30% of treated patients.   Moreover, a subset of RRMS patients with specially active MS, sometimes called "rapidly worsening MS" are normally non-responders to immunomodulators and are treated with either mitoxantrone or natalizumab.