RE: evidence about long term efficacy of CRABS

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RE: evidence about long term efficacy of CRABS

Post by jazzcat » Sun Oct 05, 2008 4:42 pm

Hi all,

Just curious. I am on Rebif and have been stable with no relapses and no new symptoms for 5 years! YAY!

I have heard from some fellow people with MS who choose to go drug free that Rebif and Avonex are effective only in the first couple of years and then lose their effectiveness.

I am on the web exploring this idea. Any thoughts or links to articles that might set me on a path to greater understanding?

Thanks in advance for your responses!

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Post by dignan » Sun Oct 05, 2008 7:36 pm

Here are a few abstracts that might be helpful. I don't know if the full articles are freely available...I also don't know why the Italians are so interested in this stuff...

PRISMS-4: Long-term efficacy of interferon-beta-1a in relapsing MS.

Neurology. 2001 Jun 26;56(12):1628-36.
PRISMS Study Group and the University of British Columbia MS/MRI Analysis Group..

BACKGROUND: The PRISMS study demonstrated significant clinical and MRI benefit at 2 years for interferon-beta-1a, 22 and 44 mcg thrice weekly (tiw), compared with placebo in relapsing-remitting MS. Years 3 and 4 extension study results are reported.

METHODS: Patients initially receiving placebo were randomized to blinded interferon-beta-1a, 22 or 44 mcg tiw (n = 172; crossover group); others continued blinded treatment with their originally assigned dose, 22 mcg (Rx22 group) or 44 mcg (Rx44 group) tiw (n = 167 per group). Patients had 3- to 6-month clinical and annual MRI assessments.

RESULTS: Relapse rates for 4 years were 1.02 (crossover), 0.80 (Rx22, p < 0.001), and 0.72 (Rx44, p < 0.001); the dose effect approached significance (p = 0.069; risk ratio, 0.88; 95% CI, 0.76-1.01). Crossover groups showed reductions in relapse count, MRI activity, and lesion-burden accumulation with interferon-beta-1a compared with their placebo period (p < 0.001 both doses). Time to sustained disability progression was prolonged by 18 months in the Rx44 group compared with the crossover group (p = 0.047). Rx22 and Rx44 reduced new T2 lesion number and lesion burden compared with crossover (p < 0.001); Rx44 was superior to Rx22 on several clinical and MRI outcomes. Persistent neutralizing antibodies developed in 14.3% (Rx44) and 23.7% (Rx22) of patients and were associated with reduced efficacy.

CONCLUSIONS: Clinical and MRI benefit continued for both doses up to 4 years, with evidence of dose response. Outcomes were consistently better for patients treated for 4 years than for patients in crossover groups. Efficacy decreased with neutralizing antibody formation.

Pubmed link

High-dose, frequently administered interferon beta therapy for relapsing-remitting multiple sclerosis must be maintained over the long term: the interferon beta dose-reduction study.

J Neurol Sci. 2004 Jul 15;222(1-2):13-9.
Barbero P, Verdun E, Bergui M, Pipieri A, Clerico M, Cucci A, Ricci A, Bergamasco B, Durelli L.
Divisione di Neurologia, Ospedale San Luigi Gonzaga, Regione Gonzole, Via Cherasco, 15, 10-I 10043 Orbassano, Turin, Italy.

Long-term trials have demonstrated the continued efficacy of interferon (IFN) beta treatment in patients with relapsing-remitting (RR) multiple sclerosis (MS) during prolonged administration. The objective of the work was to evaluate the effects of reducing IFN beta administration frequency and total weekly dose in patients with RR MS who have achieved clinical and MRI disease activity stabilization during long-term IFN beta-1b treatment. Prospective 1-year follow-up of 27 RR MS patients on long-term 250 microg every other day (standard dose) IFN beta-1b treatment were randomized either to gradually reduce dose to 30 microg once-a-week IFN beta-1a (13 patients), or to continue on IFN beta-1b standard dose (14 patients).

We found significant differences in the two group of patients. In the group of patients continuously treated with IFN beta-1b standard dose, 79% remained relapse free compared to 23% in the group receiving once-weekly IFN beta-1a (p=0.006). The number of patients without new PD/T2 lesions was higher in the group of patients continuously treated with IFN beta-1b standard dose (77%) compared to the once-weekly IFN beta-1a group (23%) (p=0.04). IFN beta is a long-term treatment for MS. The reduction of IFN beta-1b administration frequency and dose is not advisable even in patients free from clinical and MRI disease activity for many years.

Pubmed link

Effects of interferon beta-1a and -1b over time: 6-year results of an observational head-to-head study.

Acta Neurol Scand. 2006 Apr;113(4):241-7.
Patti F, Pappalardo A, Florio C, Politi G, Fiorilla T, Reggio E, Reggio A.
Centro Sclerosi Multipla, Università di Catania, Catania, Italy.

OBJECTIVE: To evaluate and compare the long-term efficacy and safety of two different beta-interferon preparations (IFN-beta-1a vs IFN-beta-1b).

MATERIALS AND METHODS: Two parallel outpatient groups with relapsing-remitting multiple sclerosis (RRMS), according to Poser criteria, were treated with either intramuscular IFN-beta-1a 30 microg (group A, n = 62) or subcutaneous IFN-beta-1b 250 microg (group B, n = 64).

RESULTS: A statistically significant reduction was seen in the relapse rate (P < 0.0001) in both groups. No significant difference was found between the two groups (P = 0.43). After 6 years of therapy, the mean Expanded Disability Status Scale score was 3.22 +/- 1.47 (delta 1.03 +/- 1.35) in group A and 3.34 +/- 1.47 (delta 0.97 +/- 1.47) in group B (P = 0.47).

CONCLUSIONS: Our study results suggest that the efficacy of IFN-beta-1a 30 microg once weekly and SC IFN-beta-1b 250 microg every other day is similar. Both IFN-beta-1a and IFN-beta-1b are effective in slowing disability progression.

Pubmed link

Long-term clinical experience with weekly interferon beta-1a in relapsing multiple sclerosis.

Eur J Neurol. 2006 Sep;13(9):1014-21.
Coppola G, Lanzillo R, Florio C, Orefice G, Vivo P, Ascione S, Schiavone V, Pagano A, Vacca G, De Michele G, Morra VB.
Department of Neurological Sciences, Federico II University, Naples, Italy.

Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of interferon beta-1a (IFNbeta-1a) therapy in multiple sclerosis (MS) patients. The goals of this study were to (i) assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFNbeta-1a therapy in a large cohort of patients, and (ii) suggest possible predictors of therapeutic response. A total of 255 patients were included in the study. Mean time on therapy was 31.7 +/- 19.3 months.

Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of cholesterol levels. After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline. The mean annual relapse rate was reduced compared with baseline. Patients with < or = 2 relapses in the previous 2 years and with baseline EDSS scores of < or = 2 had a longer estimated time to first relapse and to progression and first relapse, respectively. These results confirm the safety and suggest a sustained effectiveness of i.m. IFNbeta-1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.

Pubmed link

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thanks for posting

Post by jazzcat » Thu Oct 16, 2008 4:40 pm

Hey, Dignan,

Thanks for posting the information. It helps settle my mind.


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