TY - JOUR
T1 - Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC)
AU - Bus, S. R. M.
AU - Zambreanu, L.
AU - Abbas, A.
AU - Rajabally, Y. A.
AU - Hadden, R. D. M.
AU - de Haan, R. J.
AU - de Borgie, C. A. J. M.
AU - Lunn, M. P.
AU - van Schaik, I. N.
AU - Eftimov, F.
AU - on behalf of the OPTIC study group
AU - Vrancken, A. F. J. E.
AU - van Doorn, P. A.
AU - Hoeijmakers, J. G. J.
AU - Voermans, N.
AU - Wirtz, P. W.
AU - Padberg, M.
AU - de Rijk, M.
AU - Chavada, G.
AU - Miller, J.
AU - Holt, J.
N1 - Funding Information: YAR reports receiving speaker/consultancy honoraria from LFB, CSL Behring, Octapharma and Kedrion, serving on scientific advisory boards for CSL Behring and LFB, education sponsorships from LFB and CSL Behring and research grants from LFB and CSL Behring. RDMH received personal and departmental payments from CSL Behring and Grifols. RJdH reports no competing interests. CAJMdB reports no competing interests. MPL reports serving on scientific advisory boards for CSL, Polyneuron, Novartis and UCB Pharma all outside this work. His institution has received PI investigator fees on his behalf from Novartis and UCB Pharma. INvS reports departmental honoraria for serving on scientific advisory boards for CSL Behring and Kedrion. He chaired a steering committee for CSL Behring. He is a member of the Scientific Board of the Kreuth III meeting. FE reports grants from Prinses Beatrix Spierfonds, Netherlands Organization for Health Research and Development, and a consulting fee from CSL Behring and UCB Pharma that was paid to Institution, outside the submitted work. As PI of INCbase, an international CIDP Registry and Biobank, he has received grants from CSL Behring, Takeda Pharmaceutical Company, Kedrion and Terumo BCT. Funding Information: This manuscript was written on behalf of the OPTIC-study group consisting of the authors of this manuscript and investigators listed in the ?List of investigators?. Janneke Zwiers, Hobert Smink and all home care nurses from Sanquin Plasma Products b.v., for offering logistical support as well as facilitating home care treatments. Members of the DSMB: Thomas Harbo, Joke Dijk, Gabor Linthorst. Data safety and monitoring board (DSMB) member list Thomas Harbo (chair), Neurologist, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Gabor Linthorst (member), Endocrinologist, Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Joke Dijk (member), Clinical epidemiologist/Neurologist, Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. OPTIC-study group : A.F.J.E. Vrancken, University Medical Centre Utrecht (UMCU), Department of Neurology, Utrecht; P.A. van Doorn, Erasmus University Medical Centre (EMC), Department of Neurology, Rotterdam; J.G.J. Hoeijmakers, Maastricht University Medical Centre (MUMC), Department of Neurology, Maastricht; N. Voermans, Department of Neurology, Radboud University Medical Centre (RUMC), Nijmegen; P.W. Wirtz, Haga Hospital, Department of Neurology, The Hague; M. Padberg, Martini Hospital Groningen, Department of Neurology, Groningen; M. de Rijk, Catharina Hospital Eindhoven, Department of Neurology, Eindhoven. G. Chavada, Queen Elizabeth University Hospital, Department of Neurology, Glasgow; J. Miller, Royal Victoria Infirmary, Department of Neurology, Newcastle upon Tyne; J. Holt, The Walton Centre, Department of Neurology, Liverpool. SRMB, LZ, AA, RAY, RDMH, RJdH, CAJMB, MPL, INvS and FE contributed substantially to the conception and design of the study. Funding Information: ZonMW: grant support. Princess Beatrix Spierfonds (Dutch Charity): grant support. Sanquin Plasma Products (Dutch Blood Supply Foundation): logistical support. Funders have no role in study design, data collection and analysis, decision to publish or preparation of (future) manuscript(s). MPL is supported by the UCLH NHS Foundation Trust Biomedical Research Centre, but no funding was received directly for this project. LZ received funding from the GBS/CIDP Foundation International and GAIN UK (Guillain-Barré & Associated Inflammatory Neuropathies). Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone. Methods: An international, randomised, double-blind, placebo-controlled trial, in adults with ‘probable’ or ‘definite’ CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3–5 days) followed by 6 courses of IVIg 1/g/kg (over 1–2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety. Discussion: In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed. Trial registration: ISRCTN registry ISRCTN15893334. Prospectively registered on 12 February 2018.
AB - Background: International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone. Methods: An international, randomised, double-blind, placebo-controlled trial, in adults with ‘probable’ or ‘definite’ CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3–5 days) followed by 6 courses of IVIg 1/g/kg (over 1–2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety. Discussion: In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed. Trial registration: ISRCTN registry ISRCTN15893334. Prospectively registered on 12 February 2018.
KW - CIDP
KW - Chronic inflammatory demyelinating polyradiculoneuropathy
KW - Corticosteroids
KW - IVIg
KW - IVMP
KW - Intravenous immunoglobulins
KW - Methylprednisolone
KW - RCT
KW - Randomised controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85101270160&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13063-021-05083-1
DO - https://doi.org/10.1186/s13063-021-05083-1
M3 - Article
C2 - 33608058
SN - 1745-6215
VL - 22
JO - Trials
JF - Trials
IS - 1
M1 - 155
ER -