Monday, 31 August 2015

ClinicSpeak: glatiramer acetate experience and persistence

Glatiramer acetate, Teva's cash-cow, has plenty of life left in it! #ClinicSpeak #MSBlog #MSResearch

"I am often asked is there a future for the injectable DMTs. My knee jerk response is yes; the injectables are safe and there a large number of responders out there who will almost certainly want to stay on their current medication. Why? There is no data suggesting that if you are a responder to one class of drug that if you then move to a new class of therapy that you are likely to be a responder to the new class. Interestingly, the study below suggests that interferon-beta failures who switched to glatiramer acetate (GA) do better on GA than those starting the drug as naive to DMTs. Could this observation be telling us about the biology of MS and the DMTs we use to control the disease?"

"Another reason why GA is here to stay is the fact that its safety record in pregnancy is very favourable. This is based on large pregnancy registries that show GA is not teratogenic, i.e. it has not been shown to cause malformations in the foetus, it is not an abortifacient, i.e. increased loss of early pregnancies, it does not affect fertility, i.e. you ability to fall pregnant, it has not impact on labour and it is safe for breastfeeding. In short, out of all the currently licensed maintenance DMTs, GA is the only one that can make these claims."

"You are also probably aware that Teva, who manufacture GA, have now launched a 40 mg three times a week formulation (Copaxone-40), that looks to be as effective as the daily injection formulation (Copaxone-20). If you had an option why wouldn't you switch from the 20 mg daily formulation to the to 40 mg 3x per week formulation? You may not if it is due to affordability. In many countries generic versions of GA are about to be launched; in price-sensitive markets, which are most markets, cheaper versions of GA will disrupt the market."

"Finally, if we could only predict who will be a responder, or non-responder, to GA prior to them starting on treatment then GA will have plenty of life left in it. Who wouldn't you start GA if we could say your chances of responding to this drug (NEDA-3) are greater than 80% or 90%? It is all about risks and benefits; if only we can tip the ratio in favour of the benefits. May be I am wrong?"

Fern├índez-Fournier et al. Differential glatiramer acetate treatment persistence in treatment-naive patients compared to patients previously treated with interferon. BMC Neurol. 2015 Aug ;15:141. doi: 10.1186/s12883-015-0399-9.

BACKGROUND: In the treatment of multiple sclerosis, a change of therapy is considered after treatment failure or adverse events. Although disease modifying drugs' (DMD) efficacy and side effects have been fully analysed in clinical trials, the effects of previous therapy use are less well studied. 

AIMS: We aimed to study medication persistence with glatiramer acetate in treatment-naive patients and in patients previously treated with interferon.

METHODS: A retrospective study of relapsing-remitting multiple sclerosis patients treated with glatiramer acetate in an MS Unit of a Spanish University Hospital (January 2004 - September 2013). Treatment time on glatiramer acetate was studied. Reasons for treatment discontinuation were considered as follows: lack of efficacy, serious adverse event, injection-related side effect, pregnancy and lost to follow-up. Use of prior DMD was registered and analysed. Homogeneity of groups was analysed using Fisher's and Mann-Whitney's tests. The Kaplan Meier method and Cox regression model were used to estimate time to and risk of treatment discontinuation.

RESULTS: In total, 155 relapsing-remitting multiple sclerosis patients were treated with glatiramer acetate: 100 treatment-naive patients and 55 treated previously with interferon. At the end of the study, 76 patients (49.0 %) continued on glatiramer acetate (with an average treatment time (ATT) of 50.4 months, s.d.32.8) and 50 patients (32.3 %) had switched therapy: 27 patients (17.4 %) for inefficacy (ATT 29.2 months, s.d.17.5), 20 patients (12.9 %) for injection site reactions (ATT 16.5 months, s.d.20.3) and 3 patients (1.9 %) after serious adverse events (ATT 15.7 months, s.d.15.1). ATT in our cohort was 39 months (s.d.30.0), median follow-up 34 months. Six months after glatiramer acetate initiation, probability of persisting on GA was 91.4 %, 82.5 % after 12 months and 72.5 % after 2 years. The risk of glatiramer acetate treatment discontinuation was 2.8 [1.7 - 4.8] times greater for treatment-naive patients than for patients treated previously with interferon and this was hardly modified after adjusting for sex and age.

CONCLUSIONS: Glatiramer acetate was safe and useful with low rates of serious adverse events and low rates of break-through disease. Injection intolerance proved a major limitation to glatiramer acetate use. Patients who had been previously treated with interferons presented a lower probability of glatiramer acetate discontinuation than treatment-naive patients.

CoI: multiple

Fingolimod in the real world

Totaro R, Di Carmine C, Costantino G, Fantozzi R, Bellantonio P, Fuiani A, Mundi C, Ruggieri S, Marini C, Carolei A. Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study.
Mult Scler Int. 2015;2015:763418. doi: 10.1155/2015/763418.

Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

        Fingo in the real world gets it up their with the big boys