Abstract
Background and Aims:
The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga®) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings.
Methods:
Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks.
Results:
All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64–90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication.
Interpretation:
Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP.
Clinical trial numbers:
EudraCT 2015-005443-14, NCT02638207.
| Original language | English |
|---|---|
| Pages (from-to) | 835-845 |
| Number of pages | 11 |
| Journal | Drug Safety |
| Volume | 46 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sept 2023 |
Bibliographical note
Funding Information:This study was sponsored by Octapharma Pharmazeutika Produktionsges.m.b.H. (Vienna, Austria) who thank investigators, trial personnel and patients for their participation. Medical writing assistance was provided by nspm ltd, Meggen, Switzerland, and funded by Octapharma. The members of ProCID study investigators: Bulgaria S Kastrev and V Rizova, Multiprofile Hospital for Active Treatment Puls AD, Blagoevgrad; I Milanov, University Neurological Hospital St. Naum, Sofia. Canada R Massie, Montreal Neurological Hospital, Montreal. Czech Republic R Taleb and M Bednar, Private Neurology Practice, Hradec Kralove; P Ridzon, Thomayers Hospital, Prague. Germany J Schmidt and J Zschüntzsch, University Medical Center Göttingen. Hungary R Csilla, Jahn Ferenc Del‐pesti Hospital, Budapest; L Vécsei, University of Szeged, Szeged. Poland K Rejdak, Medical University of Lublin; M Koszewicz and S Budrewicz, Wroclaw Medical University, Wroclaw. Romania A Docu-Axelerad, Spitalul Clinic Judetean de Urgenta “Sf. Apostol Andrei”, Constanta; A Dulamea and M Marian, University of Medicine and Pharmacy "Carol Davila" Fundeni Clinical Institute, Bucharest; A. Kadar and L Zecheru-Lapusneanu, Teo Health Brasov, Brasov. Russia V Mikhailov and D Zakharov, Bekhterev National Research Medical Center for Psychiatry and Neurology, St. Petersburg; N Suponeva and M Piradov, Russian Academy of Sciences Research Center of Neurology, Moscow. Ukraine N Smolko and D Smolko, Vinnytsya National Medical University, Vinnytsya.
Funding Information:
This study was sponsored by Octapharma Pharmazeutika Produktionsges.m.b.H. (Vienna, Austria) who thank investigators, trial personnel and patients for their participation. Medical writing assistance was provided by nspm ltd, Meggen, Switzerland, and funded by Octapharma. The members of ProCID study investigators: Bulgaria S Kastrev and V Rizova, Multiprofile Hospital for Active Treatment Puls AD, Blagoevgrad; I Milanov, University Neurological Hospital St. Naum, Sofia. Canada R Massie, Montreal Neurological Hospital, Montreal. Czech Republic R Taleb and M Bednar, Private Neurology Practice, Hradec Kralove; P Ridzon, Thomayers Hospital, Prague. Germany J Schmidt and J Zschüntzsch, University Medical Center Göttingen. Hungary R Csilla, Jahn Ferenc Del‐pesti Hospital, Budapest; L Vécsei, University of Szeged, Szeged. Poland K Rejdak, Medical University of Lublin; M Koszewicz and S Budrewicz, Wroclaw Medical University, Wroclaw. Romania A Docu-Axelerad, Spitalul Clinic Judetean de Urgenta “Sf. Apostol Andrei”, Constanta; A Dulamea and M Marian, University of Medicine and Pharmacy "Carol Davila" Fundeni Clinical Institute, Bucharest; A. Kadar and L Zecheru-Lapusneanu, Teo Health Brasov, Brasov. Russia V Mikhailov and D Zakharov, Bekhterev National Research Medical Center for Psychiatry and Neurology, St. Petersburg; N Suponeva and M Piradov, Russian Academy of Sciences Research Center of Neurology, Moscow. Ukraine N Smolko and D Smolko, Vinnytsya National Medical University, Vinnytsya.
Funding Information:
D.R.C. reports consulting for Amgen Inc., Annexon Biosciences, Boehringer Ingelheim, Grifols S.A., Johnson & Johnson, Neura Bio, Novartis, Octapharma AG, Pfizer Inc., Roche, Seattle Genetics Inc., Valenzabio. D.R.C. is on the Data Safety Monitoring Board for the following: PledPharma, Hansa Medical, and Mitsubishi Tanabe Pharma Corporation. D.R.C. is on the Scientific Advisory Board for Sinomab, Algotherapeutics, Nervosave. D.R.C. received royalties for technology licensing from Worldwide Clinical Trials, Inc., CMIC, MedImmune Ltd., RWS Life Sciences, Levicept, AstraZeneca Pharmaceuticals, LP, Genentech, Inc., Chiesi Farmaceutici S.p.A., Beijing 3E-Regenacy Pharmaceuticals Co., Passage Bio, and Disarm Therapeutics, outside the submitted work. P.A.v.D. reports grants from Sanquin Blood Supply Prinses Beatrix Spierfonds, and Takeda during the conduct of the study; and consulting fees from Annexion, Argenx, Octapharma, and Hansa, all outside the submitted work. All grants and consulting fees are transferred to the Erasmus MC Research fund. H.P.H. reports consulting for CSL Behring, Sanofi Genzyme, and UCB. H.P.H. received payments or honoraria from CSL Behring and Octapharma. I.S.J.M. reports grants from Talecris Talents program, GBS/CIDP Foundation International and FP7 EU program, outside the submitted work. Furthermore, a research foundation at the University of Maastricht received honoraria on behalf of him for participation in steering committees of the Talecris Immune Globulin Intravenous For Chronic Inflammatory Demyelinating Polyneuropathy Study, Commonwealth Serum Laboratories, Behring, Octapharma, LFB, Novartis, Union Chimique Belge, Johnson & Johnson, Argenx, outside the submitted work. And Octapharma during the conduct of the study. H.D.K. is on Steering Committees for Octapharma and Sanofi Genzyme. H.D.K. reports travel support and consulting fees from Octapharma in relation to a study design advisory board. H.D.K. reports consulting for UCB, Terumo, Akcea, Alnylam, CSL Behring, Merz, Pfizer, Roche and Dyne. H.D.K. is on Data Safety Monitoring Boards or Advisory Boards for UCB, Syneos and Octapharma. H.D.K. received a grant from Takeda for investigator-initiated research. D.H. and E.C. are employees of Octapharma PPG, Vienna, Austria.
Publisher Copyright:
© 2023, The Author(s).