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Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results.

Butzkueven H, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, Zhang A, Hotermans C, Belachew S, TYSABRI Observational Program (TOP) Investigato - J. Neurol. Neurosurg. Psychiatr. (2014)

Bottom Line: Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals.Mean EDSS scores remained unchanged up to 5 years.NCT00493298.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia Department of Neurology, Box Hill Hospital, Monash University, Victoria, Victoria, Australia.

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Annualised relapse rate after initiation of natalizumab according to (A) baseline characteristics, (B) combined baseline relapse status and number of prior disease-modifying therapies (DMTs) and (C) baseline treatment history.*p Value from a negative binomial regression model adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), relapse status in the past year (≤1 vs >1), prior DMT use (0, 1 and >1), disease duration (≥8 vs <8 years) and treatment duration (≥3 vs <3 years). †p=0.697 between comparator groups at baseline on the basis of a negative binominal model for baseline annualised relapse rate (adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), disease duration (<8 vs ≥8 years) and treatment duration (<3 vs ≥3 years)). ‡p<0.0001 for difference among groups after treatment is from negative binomial model adjusted for sex, baseline relapse status (0 or 1 relapse vs >1), EDSS score (<3.0 vs ≥3.0), treatment duration (<3 vs ≥3 years) and disease duration (<8 vs ≥8 years). Error bars indicate 95% CIs. DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; GA, glatiramer acetate; IFN, interferon β-1; IS, immunosuppressant.
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JNNP2013306936F2: Annualised relapse rate after initiation of natalizumab according to (A) baseline characteristics, (B) combined baseline relapse status and number of prior disease-modifying therapies (DMTs) and (C) baseline treatment history.*p Value from a negative binomial regression model adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), relapse status in the past year (≤1 vs >1), prior DMT use (0, 1 and >1), disease duration (≥8 vs <8 years) and treatment duration (≥3 vs <3 years). †p=0.697 between comparator groups at baseline on the basis of a negative binominal model for baseline annualised relapse rate (adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), disease duration (<8 vs ≥8 years) and treatment duration (<3 vs ≥3 years)). ‡p<0.0001 for difference among groups after treatment is from negative binomial model adjusted for sex, baseline relapse status (0 or 1 relapse vs >1), EDSS score (<3.0 vs ≥3.0), treatment duration (<3 vs ≥3 years) and disease duration (<8 vs ≥8 years). Error bars indicate 95% CIs. DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; GA, glatiramer acetate; IFN, interferon β-1; IS, immunosuppressant.

Mentions: Significant associations between baseline disease characteristics and annualised relapse rates on natalizumab therapy were observed (figure 2). Lower mean on-therapy annualised relapse rates were associated with lower baseline EDSS scores, fewer relapses in the prior year and fewer DMTs used prior to natalizumab (figure 2A). When therapy history and baseline relapse status were analysed together, the lowest on-therapy annualised relapse rates were seen in patients with a history of only one relapse in the prior 12 months who were either therapy naïve or had received only one DMT prior to natalizumab; those with greater numbers of relapses and/or DMTs had higher rates (0.16 to 0.18 vs 0.23 to 0.40; p<0.0001) (figure 2B). While patients treated with natalizumab had significant reductions in annualised relapse rate regardless of treatment history, annualised relapse rates were lowest in patients who were therapy naïve at baseline and highest in those patients with prior IS use (figure 2C). In pairwise comparisons, annualised relapse rates were significantly different for the therapy-naïve group versus each of the other groups and for any of the comparisons of GA and/or IFN use groups versus the prior IS use group (p<0.05).


Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results.

Butzkueven H, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, Zhang A, Hotermans C, Belachew S, TYSABRI Observational Program (TOP) Investigato - J. Neurol. Neurosurg. Psychiatr. (2014)

Annualised relapse rate after initiation of natalizumab according to (A) baseline characteristics, (B) combined baseline relapse status and number of prior disease-modifying therapies (DMTs) and (C) baseline treatment history.*p Value from a negative binomial regression model adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), relapse status in the past year (≤1 vs >1), prior DMT use (0, 1 and >1), disease duration (≥8 vs <8 years) and treatment duration (≥3 vs <3 years). †p=0.697 between comparator groups at baseline on the basis of a negative binominal model for baseline annualised relapse rate (adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), disease duration (<8 vs ≥8 years) and treatment duration (<3 vs ≥3 years)). ‡p<0.0001 for difference among groups after treatment is from negative binomial model adjusted for sex, baseline relapse status (0 or 1 relapse vs >1), EDSS score (<3.0 vs ≥3.0), treatment duration (<3 vs ≥3 years) and disease duration (<8 vs ≥8 years). Error bars indicate 95% CIs. DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; GA, glatiramer acetate; IFN, interferon β-1; IS, immunosuppressant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215289&req=5

JNNP2013306936F2: Annualised relapse rate after initiation of natalizumab according to (A) baseline characteristics, (B) combined baseline relapse status and number of prior disease-modifying therapies (DMTs) and (C) baseline treatment history.*p Value from a negative binomial regression model adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), relapse status in the past year (≤1 vs >1), prior DMT use (0, 1 and >1), disease duration (≥8 vs <8 years) and treatment duration (≥3 vs <3 years). †p=0.697 between comparator groups at baseline on the basis of a negative binominal model for baseline annualised relapse rate (adjusted for sex, baseline EDSS score (<3.0 vs ≥3.0), disease duration (<8 vs ≥8 years) and treatment duration (<3 vs ≥3 years)). ‡p<0.0001 for difference among groups after treatment is from negative binomial model adjusted for sex, baseline relapse status (0 or 1 relapse vs >1), EDSS score (<3.0 vs ≥3.0), treatment duration (<3 vs ≥3 years) and disease duration (<8 vs ≥8 years). Error bars indicate 95% CIs. DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; GA, glatiramer acetate; IFN, interferon β-1; IS, immunosuppressant.
Mentions: Significant associations between baseline disease characteristics and annualised relapse rates on natalizumab therapy were observed (figure 2). Lower mean on-therapy annualised relapse rates were associated with lower baseline EDSS scores, fewer relapses in the prior year and fewer DMTs used prior to natalizumab (figure 2A). When therapy history and baseline relapse status were analysed together, the lowest on-therapy annualised relapse rates were seen in patients with a history of only one relapse in the prior 12 months who were either therapy naïve or had received only one DMT prior to natalizumab; those with greater numbers of relapses and/or DMTs had higher rates (0.16 to 0.18 vs 0.23 to 0.40; p<0.0001) (figure 2B). While patients treated with natalizumab had significant reductions in annualised relapse rate regardless of treatment history, annualised relapse rates were lowest in patients who were therapy naïve at baseline and highest in those patients with prior IS use (figure 2C). In pairwise comparisons, annualised relapse rates were significantly different for the therapy-naïve group versus each of the other groups and for any of the comparisons of GA and/or IFN use groups versus the prior IS use group (p<0.05).

Bottom Line: Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals.Mean EDSS scores remained unchanged up to 5 years.NCT00493298.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia Department of Neurology, Box Hill Hospital, Monash University, Victoria, Victoria, Australia.

Show MeSH
Related in: MedlinePlus