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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

Flow diagram of single-center trialTen patients were screened, gave consent, and were enrolled in the trial. All 10 patients received the full study intervention and completed the trial at 30-day follow-up.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4202676&req=5

Figure 1: Flow diagram of single-center trialTen patients were screened, gave consent, and were enrolled in the trial. All 10 patients received the full study intervention and completed the trial at 30-day follow-up.

Mentions: Ten patients were screened for eligibility, enrolled, given the intervention, and followed up 30 days later for examination to complete the study (figure 1). Five of the 10 patients met the Wingerchuk 2006 clinical criteria for NMO,7 4 of whom were positive for the NMO-IgG. The other 5 subjects carried a diagnosis of NMO spectrum disorder, as they were seropositive for the NMO-IgG in the context of transverse myelitis or optic neuritis but did not meet all clinical criteria.8 Seven of the 10 presented with acute transverse myelitis and 3 presented with acute optic neuritis (table).


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

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

Flow diagram of single-center trialTen patients were screened, gave consent, and were enrolled in the trial. All 10 patients received the full study intervention and completed the trial at 30-day follow-up.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4202676&req=5

Figure 1: Flow diagram of single-center trialTen patients were screened, gave consent, and were enrolled in the trial. All 10 patients received the full study intervention and completed the trial at 30-day follow-up.
Mentions: Ten patients were screened for eligibility, enrolled, given the intervention, and followed up 30 days later for examination to complete the study (figure 1). Five of the 10 patients met the Wingerchuk 2006 clinical criteria for NMO,7 4 of whom were positive for the NMO-IgG. The other 5 subjects carried a diagnosis of NMO spectrum disorder, as they were seropositive for the NMO-IgG in the context of transverse myelitis or optic neuritis but did not meet all clinical criteria.8 Seven of the 10 presented with acute transverse myelitis and 3 presented with acute optic neuritis (table).

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