Objectives: To evaluate safety and efficacy of add-on low-dose azathioprine or interferon (IFN)-beta in patients with active multiple sclerosis despite monotherapy.
Methods: This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either IFN-beta or azathioprine, who received add-on azathioprine or IFN-beta, respectively. In a subgroup of 23 patients, 10-year data were analysed. Clinical (relapse frequency, disability) and laboratory effects were compared preceding and following the addition of second drug and between the two treatment regimens. Potential serious adverse events were evaluated.
Results: The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts decreased, being below the physiological levels in 8-26% and 13-52% of patients at each time point, respectively. The drop in relapse rate was independent from the dosage of azathioprine or changes in lymphocyte count. Comparison between the two treatment regimens showed that, with the exception of lymphocyte count, these effects were triggered by the add-on of interferon but not azathioprine. The combination therapy was well tolerated; however, after 5 years on treatment a moderately increased incidence of cancer was observed.
Conclusions: IFN-beta as add-on to azathioprine decreases relapse activity in active multiple sclerosis. In contrast, azathioprine add-on in patients with suboptimal response to IFN-beta does not improve the control over the disease activity.