By Chris Berrie
PRAGUE, CZECH REPUBLIC -- October 15, 2007 -- The addition of azathioprine to standard treatment with interferon beta-1b (IFNbeta-1b) can be maintained over 2 years with only a mild increase in adverse effects in patients with secondary progressive multiple sclerosis (MS), according to results of a multicentre, randomised, comparative, double-blind study.
Principal investigator Enrico Montanari, MD, Professor in Medicinal Psychology, Department of Internal Medicine, MS Centre, Fidenza, Italy, presented the study findings here on October 12 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Secondary progressive MS is characterised by continuous worsening disability and can be accompanied by relapses after varying periods of relapsing-remitting disease. "With secondary progressive multiple sclerosis there remains no therapy, so from the background of other studies, we decided to investigate this combination therapy," Dr. Montanari said.
The aim of the study was thus to assess the efficacy, safety and tolerability of azathioprine when added to IFNbeta-1b in patients with secondary progressive MS who had an incomplete response to IFNbeta-1b.
The study provides an overall evaluation of illness stabilisation, with the primary endpoint being the variation in MS functional composite (MSFC) over the 2-year treatment period. Secondary endpoints were Expanded Disability Status Scale (EDSS) variability, quality of life (QOL) effects according to the MSQOL-54 Instrument, cytokine and neutralising antibodies levels, and safety.
In the study, there was no significant difference between the two treatment groups in median scores on the EDSS in the previous 2 years. This evaluation considered the two treatment groups combined.
The collective baseline characteristics of the 85 patients who entered the randomisation stage demonstrated a mean age of 46.2 years, and a male/female distribution of 36/64; the EDSS profile range was: 4.0, 30.7%; 4.5, 16.0%; 5.0, 18.7%; 5.5, 5.3%; 6.0, 18.7%; 6.5, 10.7%.
There were no changes from baseline in the 6-month combined mean EDSS score variations over 2 years. Although there was an initial indication of a slight worsening in the MSFC score at 3 months (-0.10), the successive mean variations in the 6-month assessments showed maintenance of stable disease to 2 years (6, 12, 18, 24 months versus baseline): +0.02, +0.08, +0.10, +0.03, respectively.
"With the MSFC that we are using, we also see that with the ambulation index and the arms and connection functions, the results are very interesting because there is a stabilisation of these [measures]," Dr. Montanari noted.
Similarly, MSQoL-54 scores over 2 years of combined treatment show maintenance of a slight decrease from baseline scores at 6, 12, 18, and 24 months, in the composite scores of both physical health (-0.8, -1.0, -1.3, -0.8, respectively) and mental health (-2.0, -2.2, -2.1, -2.9, respectively).
The researchers observed a mild increase in adverse events with azathioprine plus IFNbeta-1b compared with IFNbeta-1b alone that involved gastrointestinal problems, an increase in liver laboratory tests and leucopoenia.
However, with a 63% rate of patient retention at the end of 2 years despite 82.4% of patients experiencing one or more adverse event, the results show good tolerability for the combination and are in line with data from other studies in patients with secondary progressive MS, the researchers noted.
Therefore, although there is a mild increase in adverse effects in the azathioprine group, this combination of IFNbeta-1b and azathioprine demonstrates good stabilisation of clinical evolution in patients with secondary progressive MS, the researchers concluded.
[Presentation title: ASPIRE: Interferon Beta-1b in Combination With Azathioprine for Secondary Progressive Multiple Sclerosis: A 2-Year, Double-Blind, Randomised, Multicentre, Pilot Study. Safety and Drop-Outs Data at 21 Months of Enrolment. Abstract P188]
