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Research Article
Sanjeev Kharel
Tribhuvan University Institute of Medicine
Corresponding Author
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Background
Interleukin-6 (IL-6) inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various IL-6 inhibitors in the management of NMO/NMOSD.
Methods
PubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients, on trial relapse risk, and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS-before and after treatment. While pooled risk ratio between the intervention group and placebo group was used in Randomized Controlled Trial (RCTs). A forest plot was prepared to indicate the efficacy outcomes.
Results
A total of nine studies with 202 patients were included in our meta-analysis. IL-6 inhibitors found a good proportion (75%,95% CI: 0.62–0.89; p<0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6 95% CI: -2.71 to -1.68; p<0.001) and on trial relapse risk (RR: 0.46; 95% CI: 0.32‐0.66; P< 0.001) but did not show significant difference in change in EDSS score (mean difference=-0.79, 95% CI: -1.89 to -0.31; p=0.16). Also, the toxicity profile of IL-6 inhibitors was acceptable considering the proportions of patients with adverse events (72%, 95% C.I.;0.59-0.84, I2=85.29%, p<0.001), proportions of patients with serious adverse events (18%;95% C.I.; -3.68 to 4.04, I2=0%, p=0.93) and zero treatment related deaths. In subgroup analysis, we found subcutaneous administration to be superior (81%;95% CI:0.74-0.82) than intravenous route (67%; 95% CI:0.67-0.89) in relapse free maintenance.
Conclusion
IL-6 inhibitor therapy showed significant benefits in reducing mean ARR, relapse risk and increasing the number of relapse-free patients with acceptable adverse events profile.
Keywords
Anti-Interleukin-6 inhibitors, Drug Therapy, NMO/NMOSD
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No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- supplementaryfile1IL6.docx
Appendix 1: Search strategy used in the current systematic review and meta-analysis. Appendix 2: Newcastle-Ottawa Scale for assessing quality of non-randomized/observational studies. Appendix 3: Cochrane Collaboration tool for assessing quality of randomized controlled trials.
- supplementaryfigure1.pdf
Supplementary Figure 1: Funnel plot for detection of publication bias in meta-analysis of proportion of patients with relapse free events. Black dots represent imputed studies and brown dot represent added studies for trim and fill. A: Without trim and fill B: After trim and fill
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CURRENT STATUS: Under Review
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Editorial decision: Major revision
On 22 Sep, 2021
Reviews received
Received 18 Sep, 2021
Reviewers agreed
On 10 Sep, 2021
Reviewers invited
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On 09 Jun, 2021
Editor invited
On 07 Jun, 2021
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On 07 Jun, 2021
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Subject Areas
Neurology
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This preprint is under consideration at BMC Neurology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Sanjeev Kharel
Tribhuvan University Institute of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 10 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 22 Sep, 2021
Reviews received
Received 18 Sep, 2021
Reviewers agreed
On 10 Sep, 2021
Reviewers invited
Invitations sent on 09 Jun, 2021
Editor assigned
On 09 Jun, 2021
Editor invited
On 07 Jun, 2021
Submission checks complete
On 07 Jun, 2021
First submitted
On 31 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Interleukin-6 (IL-6) inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various IL-6 inhibitors in the management of NMO/NMOSD.
Methods
PubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients, on trial relapse risk, and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS-before and after treatment. While pooled risk ratio between the intervention group and placebo group was used in Randomized Controlled Trial (RCTs). A forest plot was prepared to indicate the efficacy outcomes.
Results
A total of nine studies with 202 patients were included in our meta-analysis. IL-6 inhibitors found a good proportion (75%,95% CI: 0.62–0.89; p<0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6 95% CI: -2.71 to -1.68; p<0.001) and on trial relapse risk (RR: 0.46; 95% CI: 0.32‐0.66; P< 0.001) but did not show significant difference in change in EDSS score (mean difference=-0.79, 95% CI: -1.89 to -0.31; p=0.16). Also, the toxicity profile of IL-6 inhibitors was acceptable considering the proportions of patients with adverse events (72%, 95% C.I.;0.59-0.84, I2=85.29%, p<0.001), proportions of patients with serious adverse events (18%;95% C.I.; -3.68 to 4.04, I2=0%, p=0.93) and zero treatment related deaths. In subgroup analysis, we found subcutaneous administration to be superior (81%;95% CI:0.74-0.82) than intravenous route (67%; 95% CI:0.67-0.89) in relapse free maintenance.
Conclusion
IL-6 inhibitor therapy showed significant benefits in reducing mean ARR, relapse risk and increasing the number of relapse-free patients with acceptable adverse events profile.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- supplementaryfile1IL6.docx
Appendix 1: Search strategy used in the current systematic review and meta-analysis. Appendix 2: Newcastle-Ottawa Scale for assessing quality of non-randomized/observational studies. Appendix 3: Cochrane Collaboration tool for assessing quality of randomized controlled trials.
- supplementaryfigure1.pdf
Supplementary Figure 1: Funnel plot for detection of publication bias in meta-analysis of proportion of patients with relapse free events. Black dots represent imputed studies and brown dot represent added studies for trim and fill. A: Without trim and fill B: After trim and fill
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