Saturday, 26 September 2015

Factors affecting long term outcomes

Kappos L, Kuhle J, Multanen J, Kremenchutzky M, Verdun di Cantogno E, Cornelisse P, Lehr L, Casset-Semanaz F, Issard D, Uitdehaag BM. Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. J Neurol Neurosurg Psychiatry. 2015 Sep. pii: jnnp-2014-310024.

An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS).
METHODS:Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed.
RESULTS:Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥4 or ≥6, ≤5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years.
CONCLUSIONS:These findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.

The yin Yang of Beta interferon, one paper saying it doesn't lead to long term benefit, the next saying yeah. 

Hopefully the situation will be very much clearer in the era of highly effective DMT. One would hope it makes a difference in the long-term. 

Has natalizumab changed the result its been around for more than a decade. However, people getting natalizumab have more active disease and so the long term data will be skewed as the CRAB drugs are still the norm. 

Unless we start with moderestly to highly active treatment it may be difficult to see. 

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