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Persistence of seroconversion at 6 months following primary immunisation in patients with immune-mediated inflammatory diseases
  1. Luuk Wieske1,2,
  2. Eileen W Stalman1,
  3. P J Koos van Dam1,
  4. Laura Y Kummer1,3,
  5. Maurice Steenhuis3,
  6. Zoe L E van Kempen4,
  7. Joep Killestein4,
  8. Adriaan G Volkers5,
  9. Sander W Tas6,
  10. Laura Boekel7,
  11. Gertjan Wolbink3,7,
  12. Anneke Van der Kooi1,
  13. Joost Raaphorst1,
  14. Mark Löwenberg5,
  15. Bart Takkenberg5,
  16. Geert R A M D’Haens5,
  17. Phyllis I Spuls8,
  18. Marcel W Bekkenk9,
  19. Annelie H Musters9,
  20. Nicoline F Post9,
  21. Angela L Bosma9,
  22. Marc L Hilhorst10,
  23. Yosta Vegting10,
  24. Frederique J Bemelman10,
  25. Alexandre Voskuyl11,
  26. Bo Broens11,
  27. Agner Parra Sanchez5,11,
  28. Cécile A C M van Els12,13,
  29. Jelle De Wit14,15,
  30. Abraham Rutgers16,
  31. Karina de Leeuw16,
  32. Barbara Horváth17,
  33. Jan J G M Verschuuren18,
  34. Annabel M Ruiter18,
  35. Lotte van Ouwerkerk19,
  36. Diane van der Woude19,
  37. Cornelia F Allaart19,
  38. Y K Onno Teng20,
  39. Pieter van Paassen21,
  40. Matthias H Busch22,23,
  41. Papay B P Jallah23,
  42. Esther Brusse24,
  43. Pieter A van Doorn24,
  44. Adája Elisabeth Baars24,
  45. Dirkjan Hijnen25,
  46. Corine R G Schreurs25,
  47. W Ludo Van der Pol26,
  48. H Stephan Goedee26,
  49. Sofie Keijzer3,
  50. Jim Keijser3,
  51. Olvi Cristianawati3,
  52. Anja ten Brinke3,
  53. Niels J M Verstegen3,
  54. Koos A H Zwinderman27,
  55. S Marieke van Ham3,28,
  56. Taco W Kuijpers3,29,
  57. Theo Rispens3,
  58. Filip Eftimov30
  59. On behalf of the T2B! immunity against SARS-CoV-2 study group
  1. 1 Department of Neurology and Neurophysiology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  2. 2 Department of Clinical Neurophysiology, St Antonius Hospital, Nieuwegein, The Netherlands
  3. 3 Immunopathology, Sanquin Research an Landsteiner Laboratory, Amsterdam, The Netherlands
  4. 4 Department of Neurology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  5. 5 Department of Gastroenterology and Hepatology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  6. 6 Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  7. 7 Department of Rheumatology, Rheumatology and immunology Center, location Reade, Amsterdam, The Netherlands
  8. 8 Department of Dermatology, Public Health and Epidemiology; Immunity and Infections, location Academic Medical Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  9. 9 Department of Dermatology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  10. 10 Department of Internal Medicine, Section of Nephrology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  11. 11 Department of Rheumatology and Clinical Immunology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  12. 12 Centre for Infectious Disease Control, National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands
  13. 13 Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  14. 14 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
  15. 15 Center for Infectious Diseases, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
  16. 16 Rheumatology and Clinical Immunology, University Medical Center, Groningen, The Netherlands
  17. 17 Dermatology, University Medical Center Groningen, Groningen, The Netherlands
  18. 18 Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
  19. 19 Rheumatology, Leids Universitair Medisch Centrum, Leiden, The Netherlands
  20. 20 Nephrology, Leiden University Medical Centre, Leiden, The Netherlands
  21. 21 Department of Internal Medicine/Devision of Clinical & Experimental Immunology, Maastricht University Medical Centre, Maastricht, The Netherlands
  22. 22 Department of Rheumatology, Maastricht UMC+, Maastricht, The Netherlands
  23. 23 Department of Nephrology and Clinical Immunology, Maastricht Universitair Medisch Centrum+, Maastricht, The Netherlands
  24. 24 Department of Neurology, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands
  25. 25 Department of Dermatology, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands
  26. 26 Department of Neurology and Neurosurgery, Universitair Medisch Centrum, Utrecht, The Netherlands
  27. 27 Clinical Research Unit, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  28. 28 Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
  29. 29 Department of Pediatric Immunology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  30. 30 Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Eileen W Stalman, Department of Neurology and Neurophysiology, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands; e.w.stalman{at}

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Patients with immune-mediated inflammatory diseases (IMIDs) may have impaired initial humoral responses after SARS-CoV-2 vaccination depending on the type of immunosuppression (ISP) used.1 It is largely unknown how antibody titres develop over time and whether it is needed to adjust timing of booster campaigns for patients with IMID.

This is a study on long-term persistence of seroconversion after vaccination in patients with IMID on ISP, patients with IMID not on ISP and healthy controls. This study is part of an ongoing national prospective multicentre cohort study in the Netherlands (Target-to-B! study; trial ID NL8900). Participants were included from 2 February 2021 and 1 October 2021. Participants with seroconversion (ie, >4 AU/mL) after primary immunisation with either BNT162b2 or CX-024414 in whom serum samples were collected 28 days after primary immunisation and before the first additional vaccination were included. Patients with IMID on ‘strongly antibody-impairing immunosuppressants’ (ie, anti-CD20 therapies, sphingosine 1-phosphate receptor (S1PR) modulators and mycophenolate mofetil (MMF)) were offered a first additional vaccination 3 months after primary immunisation; others after 5–6 months. Participants with a SARS-CoV-2 breakthrough infection were excluded; inclusion and exclusion criteria for the overall study are described elsewhere.1 Clinical and serological data collection is described in the supplement. We measured anti-RBD IgG responses using ELISA.2 Serum samples used for this analyses were collected prior to the first additional vaccination. For analysis, patients with IMID with ‘strongly antibody-impairing immunosuppressants’ were separated from other ISPs (analysed as group and apart for the most frequently used other ISPs, ie, anti-TNF, methotrexate and purine antagonists).

A total of 877 patients with IMID with ISP (99 with ‘strongly antibody-impairing immunosuppressants’ and 778 other ISP) were compared with 356 controls (243 patients with IMID without ISP and 113 healthy controls; see online supplemental figure S1). Online supplemental table S1 shows …

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  • Handling editor Josef S Smolen

  • Twitter @koosvandam

  • LW and EWS contributed equally.

  • Contributors All authors met the criteria for authorship set by the International Committee of Medical Journal Editors. TR, MS, SK, JK, AEB and OC did the serological assays; all other authors contributed in data acquisition. LW, EWS, TWK and FE wrote the first draft of the manuscript. LW and EWS did the data analyses. EWS, LW, PJKvD and LYK had full access to and verified the underlying data. All authors helped to revise the manuscript for important intellectual content and had final responsibility for the decision to submit for publication.

  • Funding This study was supported by ZonMw (The Netherlands Organisation for Health Research and Development, grant 10430072010007).

  • Disclaimer The sponsor had no role in the design, analyses or reporting of the study.

  • Competing interests FE and TWK report (governmental) grants from ZonMw to studyimmune response after SARS-Cov-2 vaccination in autoimmune diseases. FE also reports grants from Prinses Beatrix Spierfonds, CSL Behring, Kedrion, Terumo BCT, Grifols, Takeda Pharmaceutical Company, and GBS-CIDP Foundation; consulting fees from UCB Pharma and CSlBehring; and honoraria from Grifols. AJvdK reports grants from CSLBehring and participation on an advisory board for Argen-X. ML reports agrant from Galapagos not related to this study, and honoraria from BristolMyers Squibb, Pfizer, Takeda and Tillotts. PIS is involved in clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of, for example, psoriasis and atopic dermatitis, for which financial compensation is paid to the department or hospital, and is achief investigator of the TREAT NL registry taskforce and SECURE-AD registry. MWB is a secretary for the Dutch Experimental Dermatology Board; head of the pigmentary disorders group within the Dutch Dermatology Board; and reports honoraria from Pfizer, Sanofi, Novartis, and Fondation René Touraine. JK has speaking relationships with MerckSerono, Biogen Idec, TEVA, Sanofi, Genzyme, Roche and Novartis; received financial support to his institution for researchactivities from Merck Serono, Bayer Shcering Pharma, Biogen Idec, GlaxoSmithKline (GSK), Roche, Teva, Sanofi, Genzyme and Novartis. BH reports unpaid positions as a medical adviser for several patient groups, aboard position for ERN-SKIN, and associate editor for The British Journalof Dermatology; reports grants from AbbVIe, Akari Therapeutics, Celgene and Novartis; consulting fees from UCB Pharma, Novartis, and Janssen; and honoraria from AbbVie. JJGMV reports consulting fees from Argenx, Alexion and NMD Pharma, and is a coinventor on patent applicationsbased on MuSK-related research. DJH reportsgrants from AbbVie, AstraZeneca, Janssen, LEO Pharma and UCB; honoraria from AbbVie, Galderma, Janssen, Lilly, Pfizer, Sanofi, and UCB; and a paid position on an advisory board for BIOMAP IMI. PAvD participated on an advisory board for Octapharma. PvP reports grantsfrom Alexion Pharma and GSK, and participation on advisory boards for GSK and Vifor Pharma. GRAMD’H reports consulting fees from AbbVie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, BristolMyers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, ExeliomBiosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, GSK, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity and Protagonist; honoraria from AbbVie, Arena, Galapagos, Gilead, Pfizer, Bristol MyersSquibb and Takeda; and participation on advisory boards for AbbVie, Seres Health, Galapagos, and AstraZeneca. RBT reports honoraria fromSobi and Norgine, and participation on an advisory board for Norgine. SHG is a board member of the Dutch Society of Clinical Neurophysiology (unpaid), reports grants from Prinses Beatrix Spierfonds, and receivedspeaker fees from Shire/Takeda. KAHZ reports paid data safetymonitoring board positions for Torrent and Foresee.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.