Filippini G, Del Giovane C, Vacchi L, D’Amico R, Di Pietrantonj C, Beecher D, Salanti G.

Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis

Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008933

DOI: 10.1002/14651858.CD008933.pub2

Plain language summary
Comparative efficacy and risk-benefit balance of modulator and suppressant drugs of the immune system in people with multiple sclerosis (MS)
Several immunotherapies have been used to treat MS, but their relative effectiveness is unclear due to the limited number of direct comparison studies. The authors of this review tried to assess the efficacy and the extent of adverse events of immunotherapies commonly used in people with MS. Eleven agents were studied, interferon ß-1b (IFNß-1b) (Betaseron), IFNß-1a (Rebif and Avonex), glatiramer acetate, natalizumab, mitoxantrone, methotrexate, cyclophosphamide, azathioprine, immunoglobulins, and long-term corticosteroids. Forty-four studies up to 2010 have been included in this review, comprising a total of 17,401 adults suffered from the relapsingremitting (RRMS) and the progressive types (PrMS) of MS. The treatments were short-term, the median duration being 24 months.
The results show that:
- there is high quality evidence that both natalizumab and IFNß-1a (Rebif ) can reduce relapses and disability progression compared to placebo; and they are also more effective than IFNß-1a (Avonex) in people with RRMS. Natalizumab can induce progressive multifocal leukoencephalopathy, especially with more than two years of treatment;
- IFNß-1b (Betaseron), glatiramer acetate, and mitoxantrone may also prevent relapse and disability progression in people with RRMS. These treatments are associated with possible medium and long-term side effects, and the risk-benefit balance might be unfavourable;
- IFNß-1a (Avonex), intravenous immunoglobulins, cyclophosphamide, and long-term corticosteroids have an unfavourable riskbenefit balance for people with RRMS;
- there are insufficient high quality data to clarify whether there is a favourable risk-benefit balance using azathioprine;
- nine drugs (IFNß-1b (Betaseron), IFNß-1a (Avonex and Rebif ), glatiramer acetate, mitoxantrone, methotrexate, cyclophosphamide, intravenous immunoglobulins, and long-term corticosteroids) were also studied in people with PrMS. Few studies were of high quality and no drug was shown to be effective in preventing disability progression in people with PrMS.
It is important to consider that the efficacy and the risk-benefit of all these treatments beyond two years are uncertain, and this is a very relevant point for a lifetime disease such asMS. Thus, studies on the long-term efficacy and safety of immunotherapies for MS are urgently needed. It is also worth considering that more than 70% of the included studies were sponsored by pharmaceutical companies.
This could have affected the results of this review.