Major Finding: “Real-world” multiple sclerosis patients treated with natalizumab had rates of adverse events and reduction in relapses similar to those observed in patients in phase III trials.
Data Source: Ongoing postmarketing observational study of 1,011 patients.
Disclosures: Study funded by Biogen Idec Inc.; Dr. Trojano, consulting or speaking fees from Biogen Idec and research funding from Merck Serono.
BANGKOK, THAILAND — The effects and adverse event profile of natalizumab in multiple sclerosis patients seen in highly controlled phase III trials continue to be observed in patients who are participating in an ongoing, postmarketing observational trial of the drug.
The Tysabri Observational Program (TOP) is an ongoing evaluation of the drug's effect in 1,011 patients, whose baseline characteristics were quite different from those of patients included in the AFFIRM (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis) trials, on which the drug's approval was based, said Dr. Maria Trojano, who presented the results at the World Congress of Neurology.
The AFFIRM trial lasted 2 years, and showed a 68% reduction in the relapse rate among all patients, as well as a 42% reduction in sustained EDSS progression. Natalizumab (Tysabri) was also effective in patients with highly active disease, reducing the annual relapse rate by 81%, and the EDSS progression rate by 53%. Safety was good, with a 4% rate of adverse events, 1% of which were considered serious.
The TOP study (www.clinicaltrials.gov/ct2/show/NCT00493298
The question TOP must answer, Dr. Trojano said, is: “Does natalizumab in real life produce a similar highly reducing effect on disease activity and progression, while keeping the same safety?”
At baseline, TOP's cohort was significantly older than those in AFFIRM (38 vs. 36 years), with a longer mean duration of disease (7.5 vs. 5 years), and a worse mean score on the Expanded Disability Status Scale (EDSS; 3.7 vs. 2.3). TOP patients also had a higher annual relapse rate than did AFFIRM patients (2.03 vs. 1.53), noted Dr. Trojano of the University of Bari, Italy.
As of July 2009, patients in TOP had taken a mean of 7 doses of natalizumab, giving a base of 556 person-years to evaluate.
Natalizumab was associated with a steep decline in annualized relapse rate, dropping from a mean of 2 to less than 0.5 in the first month of therapy. Throughout the next 12 months, the mean relapse rate stayed below 0.5. This pattern mirrors that seen in the AFFIRM trial, which found relapse rates below 0.5 throughout its 24-month follow-up period.
The 292 TOP patients who have completed a full 12 months of follow-up have remained clinically stable, with an EDSS score of 3.6, compared with 3.8 at baseline.
As of July 14, there had been 46 serious adverse events reported in TOP patients (4.3%). Those included 10 infections (including 4 cases of herpes zoster and 2 pneumonias); 9 hypersensitivity reactions; 19 “miscellaneous” events; and 8 events that were not yet coded.
However, Dr. Trojano said, since TOP lacked a randomized control group, an independent 5-year study will create an external patient cohort to be used for a comparison to TOP patients.
The Multiple Sclerosis Comparator Study of Efficacy of Treatment (MSCOMET) trial will provide more reliable information about the effectiveness of natalizumab.
MSCOMET will prospectively assesses clinical effectiveness of interferon-beta or glatiramer acetate in a cohort of patients with relapsing-remitting MS.
Patients will be recruited from some centers participating in the International MSBase Registry in Melbourne, Australia. The external cohort will be selected in the MSBase Registry by a propensity score-matching technique.