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Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica.

Levy M, Mealy MA - Neurol Neuroimmunol Neuroinflamm (2014)

Bottom Line: The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Status Scale (EDSS) scores.All but 1 patient returned to preattack EDSS or better and only 2 patients required escalation to plasmapheresis.Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing neurologic damage and improving outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.

ABSTRACT

Objective: To minimize complement-mediated damage in acute relapses of neuromyelitis optica (NMO) by adding treatment with a complement inhibitor, purified C1-esterase inhibitor, to the current standard of care (high-dose glucocorticoids).

Method: We conducted an open-label phase 1b safety and proof-of-concept trial in 10 patients with NMO-immunoglobulin G seropositive NMO or NMO spectrum disease (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 g of daily IV methylprednisolone, we infused 2,000 units of C1-esterase inhibitor daily for 3 days, beginning on day 1 of hospitalization. The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Status Scale (EDSS) scores.

Results: Ten patients with NMO/NMOSD were enrolled, 7 of whom presented with acute transverse myelitis and 3 with acute optic neuritis. C1-esterase inhibitor proved to be safe in all 10 patients, with no serious adverse events recorded. There were no thromboembolic events or related lab abnormalities in any of the subjects. EDSS scores dropped from a median of 4.5 on admission to 4.0 on discharge and then down to 2.5 on 30-day follow-up. All but 1 patient returned to preattack EDSS or better and only 2 patients required escalation to plasmapheresis.

Conclusions: C1-esterase inhibitor is a safe add-on therapy for patients with NMO/NMOSD presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing neurologic damage and improving outcomes. A placebo-controlled trial is necessary to confirm these findings.

Classification of evidence: This study provides Class IV evidence that for patients with NMO with acute transverse myelitis or optic neuritis, C1-esterase inhibitor is safe and improves disability.

No MeSH data available.


Related in: MedlinePlus

Box plot of EDSS scoresThe median EDSS score at baseline was 2.25, which increased to 4.5 at peak of relapse (p = 0.016). The median EDSS score at discharge was 4.0 and at 30-day follow-up was 2.5. There was a statistical difference in the EDSS scores at peak of relapse compared to 30-day follow-up (p = 0.0142) but not between baseline and 30-day follow-up (p = 1.000). Differences were calculated using Wilcoxon matched-pairs signed rank test for paired nonparametric comparisons. Error bars represent the minimum and maximum data points.
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Figure 3: Box plot of EDSS scoresThe median EDSS score at baseline was 2.25, which increased to 4.5 at peak of relapse (p = 0.016). The median EDSS score at discharge was 4.0 and at 30-day follow-up was 2.5. There was a statistical difference in the EDSS scores at peak of relapse compared to 30-day follow-up (p = 0.0142) but not between baseline and 30-day follow-up (p = 1.000). Differences were calculated using Wilcoxon matched-pairs signed rank test for paired nonparametric comparisons. Error bars represent the minimum and maximum data points.

Mentions: Although this study was not powered for efficacy and there was no control arm, we looked for a signal of efficacy by measuring the impact of C1-esterase inhibitor on disability following an acute relapse. The EDSS score was calculated for each patient at baseline before the relapse based on previous clinic notes, at the peak of relapse, upon discharge from the hospital, and again 30 days later on follow-up in the outpatient clinic. In 7 patients, the EDSS score at the peak of relapse was higher than their baseline, due to a combination of inflammation and tissue damage from the new MRI-confirmed NMO lesion (figure 2). Following a 5-day course of steroids plus a 3-day course of C1-esterase inhibitor, EDSS scores declined back to baseline or better in 9 patients. The median baseline EDSS score was 2.25, which increased to a median of 4.5 at the peak of the attack. The median EDSS score on discharge was 4.0, which was 5 days after admission for 8 of the 10 patients and 19 days after admission for 2 patients. At 30-day follow-up, the median EDSS score was 2.5, which was not statistically different from baseline (figure 3).


Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica.

Levy M, Mealy MA - Neurol Neuroimmunol Neuroinflamm (2014)

Box plot of EDSS scoresThe median EDSS score at baseline was 2.25, which increased to 4.5 at peak of relapse (p = 0.016). The median EDSS score at discharge was 4.0 and at 30-day follow-up was 2.5. There was a statistical difference in the EDSS scores at peak of relapse compared to 30-day follow-up (p = 0.0142) but not between baseline and 30-day follow-up (p = 1.000). Differences were calculated using Wilcoxon matched-pairs signed rank test for paired nonparametric comparisons. Error bars represent the minimum and maximum data points.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 3: Box plot of EDSS scoresThe median EDSS score at baseline was 2.25, which increased to 4.5 at peak of relapse (p = 0.016). The median EDSS score at discharge was 4.0 and at 30-day follow-up was 2.5. There was a statistical difference in the EDSS scores at peak of relapse compared to 30-day follow-up (p = 0.0142) but not between baseline and 30-day follow-up (p = 1.000). Differences were calculated using Wilcoxon matched-pairs signed rank test for paired nonparametric comparisons. Error bars represent the minimum and maximum data points.
Mentions: Although this study was not powered for efficacy and there was no control arm, we looked for a signal of efficacy by measuring the impact of C1-esterase inhibitor on disability following an acute relapse. The EDSS score was calculated for each patient at baseline before the relapse based on previous clinic notes, at the peak of relapse, upon discharge from the hospital, and again 30 days later on follow-up in the outpatient clinic. In 7 patients, the EDSS score at the peak of relapse was higher than their baseline, due to a combination of inflammation and tissue damage from the new MRI-confirmed NMO lesion (figure 2). Following a 5-day course of steroids plus a 3-day course of C1-esterase inhibitor, EDSS scores declined back to baseline or better in 9 patients. The median baseline EDSS score was 2.25, which increased to a median of 4.5 at the peak of the attack. The median EDSS score on discharge was 4.0, which was 5 days after admission for 8 of the 10 patients and 19 days after admission for 2 patients. At 30-day follow-up, the median EDSS score was 2.5, which was not statistically different from baseline (figure 3).

Bottom Line: The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Status Scale (EDSS) scores.All but 1 patient returned to preattack EDSS or better and only 2 patients required escalation to plasmapheresis.Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing neurologic damage and improving outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.

ABSTRACT

Objective: To minimize complement-mediated damage in acute relapses of neuromyelitis optica (NMO) by adding treatment with a complement inhibitor, purified C1-esterase inhibitor, to the current standard of care (high-dose glucocorticoids).

Method: We conducted an open-label phase 1b safety and proof-of-concept trial in 10 patients with NMO-immunoglobulin G seropositive NMO or NMO spectrum disease (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 g of daily IV methylprednisolone, we infused 2,000 units of C1-esterase inhibitor daily for 3 days, beginning on day 1 of hospitalization. The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Status Scale (EDSS) scores.

Results: Ten patients with NMO/NMOSD were enrolled, 7 of whom presented with acute transverse myelitis and 3 with acute optic neuritis. C1-esterase inhibitor proved to be safe in all 10 patients, with no serious adverse events recorded. There were no thromboembolic events or related lab abnormalities in any of the subjects. EDSS scores dropped from a median of 4.5 on admission to 4.0 on discharge and then down to 2.5 on 30-day follow-up. All but 1 patient returned to preattack EDSS or better and only 2 patients required escalation to plasmapheresis.

Conclusions: C1-esterase inhibitor is a safe add-on therapy for patients with NMO/NMOSD presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing neurologic damage and improving outcomes. A placebo-controlled trial is necessary to confirm these findings.

Classification of evidence: This study provides Class IV evidence that for patients with NMO with acute transverse myelitis or optic neuritis, C1-esterase inhibitor is safe and improves disability.

No MeSH data available.


Related in: MedlinePlus