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Evaluation of pediatric rheumatologists’ approach to rituximab use: a questionnaire study

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Abstract

Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration.

Conclusions: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests.

What is Known:

• During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring.

What is New:

• There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment.

• This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

AAV:

Antineutrophil cytoplasmic antibody–associated vasculitis

CBC:

Complete blood count

CYC:

Cyclophosphamide

DMARDs:

Disease-modifying anti-rheumatic drugs

EULAR:

European Alliance of Associations for Rheumatology

Ig:

Immunoglobulin

IVIG:

Intravenous immunoglobulin

MMF:

Mycophenolate mofetil

RTX:

Rituximab

SLE:

Systemic lupus erythematosus

TNF:

Tumor necrosis factor

References

  1. Emer JJ, Claire W (2009) Rituximab: a review of dermatological applications. J Clin Aesthetic Dermatol 2(5):29

    Google Scholar 

  2. Hellerstedt B, Ahmed A (2003) Delayed-type hypersensitivity reaction or serum sickness after rituximab treatment. Ann Oncol 14(12):1792

    Article  CAS  PubMed  Google Scholar 

  3. Kado R, Sanders G, McCune WJ (2017) Diagnostic and therapeutic considerations in patients with hypogammaglobulinemia after rituximab therapy. Curr Opin Rheumatol 29(3):228–233

    Article  CAS  PubMed  Google Scholar 

  4. Mitchell C, Crayne CB, Cron RQ (2019) Patterns of B cell repletion following rituximab therapy in a pediatric rheumatology cohort. ACR Open Rheumatol 1(8):527–532

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brunner HI, Nicolino R (2021) Therapeutics: biologics and small molecules. In: Ross E, Petty RML, Lindsley CB, Wedderburn LR, Mellins ED, Fuhlbrigge RC (eds) Textbook of pediatric rheumatology, 8th edn. Elsevier, Philadelphia, pp 175–194

  6. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ (2005) The biology of CD20 and its potential as a target for mAb therapy. B Cell trophic Factors B Cell Antagonism Autoimmune Dis 8:140–174

    Article  CAS  Google Scholar 

  7. Pateinakis P, Pyrpasopoulou A (2014) CD20+ B cell depletion in systemic autoimmune diseases: common mechanism of inhibition or disease-specific effect on humoral immunity? BioMed research international 2014

  8. Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT (2021) Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis 80(1):14–25

    Article  PubMed  Google Scholar 

  9. Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA (2021) 2021 American college of rheumatology/vasculitis foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 73(8):1366–1383

    Article  CAS  PubMed  Google Scholar 

  10. Leandro MJ (2022) Rituximab: Principles of use and adverse effects in rheumatoid arthritis [updated Aug 29, 2022]. Available from: https://www.uptodate.com/contents/rituximab-principles-of-use-and-adverse-effects-in-rheumatoid-arthritis. Accessed 20 Jun 2024

  11. Mitka M (2013) FDA: Increased HBV reactivation risk with ofatumumab or rituximab. JAMA 310(16):1664

    Article  CAS  PubMed  Google Scholar 

  12. Smolen JS, Keystone EC, Emery P, Breedveld FC, Betteridge N, Burmester GR, Dougados M, Ferraccioli G, Jaeger U, Klareskog L, Kvien TK, Martin-Mola E, Pavelka K (2007) Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 66(2):143–150

    Article  CAS  PubMed  Google Scholar 

  13. Cambridge G, Leandro MJ, Teodorescu M, Manson J, Rahman A, Isenberg DA, Edwards JC (2006) B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum 54(11):3612–3622

    Article  CAS  PubMed  Google Scholar 

  14. Jansen MHA, Rondaan C, Legger GE, Minden K, Uziel Y, Toplak N, Maritsi D, van den Berg L, Berbers GAM, Bruijning P, Egert Y, Normand C, Bijl M, Foster HE, Koné-Paut I, Wouters C, Ravelli A, Elkayam O, Wulffraat NM, Heijstek MW (2023) EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: update 2021. Ann Rheum Dis 82(1):35–47

    Article  CAS  PubMed  Google Scholar 

  15. Winthrop KL (2024) Immunizations in autoimmune inflammatory rheumatic disease in adults [updated Mar 08, 2024]. Available from: https://www.uptodate.com/contents/immunizations-in-autoimmune-inflammatory-rheumatic-disease-in-adults. Accessed 20 Jun 2024

  16. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, Laidlaw TM, Legere HJ, Nallamshetty SN, Palis RI, Rao JJ, Berlin ST, Campos SM, Matulonis UA (2008) Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 122(3):574–580

    Article  CAS  PubMed  Google Scholar 

  17. van Vollenhoven RF, Emery P, Bingham CO 3rd, Keystone EC, Fleischmann R, Furst DE, Macey K, Sweetser M, Kelman A, Rao R (2010) Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol 37(3):558–567

    Article  PubMed  Google Scholar 

  18. Rao A, Kelly M, Musselman M, Ramadas J, Wilson D, Grossman W, Shenoy S (2008) Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias. Pediatr Blood Cancer 50(4):822–825

    Article  PubMed  Google Scholar 

  19. Teichmann LL, Woenckhaus M, Vogel C, Salzberger B, Schölmerich J, Fleck M (2008) Fatal Pneumocystis pneumonia following rituximab administration for rheumatoid arthritis. Rheumatology (Oxford) 47(8):1256–1257

    Article  CAS  PubMed  Google Scholar 

  20. Wingfield T, Jani M, Krutikov M, Mayer J, Uriel A, Marks J, Ustianowski AP (2011) Cryptococcal meningitis in an HIV-negative patient with rheumatoid arthritis treated with rituximab. Rheumatology (Oxford) 50(9):1725–1727

    Article  CAS  PubMed  Google Scholar 

  21. Vallet H, Houitte R, Azria A, Mariette X (2011) Cytomegalovirus colitis and hypo-IgG after rituximab therapy for rheumatoid arthritis. J Rheumatol 38(5):965–966

    Article  PubMed  Google Scholar 

  22. Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furman RR, Vose JM, Zelenetz AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Littell NR, Talley RL, Sartor O, Green D, Major EO, Bennett CL (2009) Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood 113(20):4834–4840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rutherford AI, Patarata E, Subesinghe S, Hyrich KL, Galloway JB (2018) Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: results from the British society for rheumatology biologics register for rheumatoid arthritis. Rheumatology (Oxford) 57(6):997–1001

    Article  PubMed  Google Scholar 

  24. Bergantini L, d’Alessandro M, Cameli P, Vietri L, Vagaggini C, Perrone A, Sestini P, Frediani B, Bargagli E (2020) Effects of rituximab therapy on B cell differentiation and depletion. Clin Rheumatol 39(5):1415–1421

    Article  CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Emine Nur Sunar Yayla, Deniz Gezgin Yıldırım, Pelin Esmeray Şenol, Çisem Yıldız & Sevcan A. Bakkaloğlu

  2. Clinic of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Turkey

    Emine Nur Sunar Yayla, Esra Bağlan & Semanur Özdel

  3. Clinic of Pediatric Rheumatology, İzmir Tepecik Training and Research Hospital, Izmir, Turkey

    Hatice Adıgüzel Dündar

  4. Department of Pediatric Rheumatology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey

    Amra Adrovic

  5. Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara, Turkey

    Elifsu Gözde Akbörü

  6. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, İstanbul University, Istanbul, Turkey

    Nuray Aktay Ayaz, Fatma Gül Demirkan, Vefa Guliyeva & Şerife Gül Karadağ

  7. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Emil Aliyev & Seher Şener

  8. Clinic of Pediatric Rheumatology, Tekirdağ Dr İsmail Fehmi Cumalıoğlu City Hospital, Tekirdag, Turkey

    Pınar Özge Avar Aydın

  9. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Fatma Aydın

  10. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Özge Baba, Mukaddes Kalyoncu & Hakan Kısaoğlu

  11. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey

    Balahan Bora Makay, Rana İşgüder, Zehra Kızıldağ & Erbil Ünsal

  12. Clinic of Pediatric Rheumatology, Samsun Training and Research Hospital, Samsun, Turkey

    Burcu Bozkaya Yücel

  13. Clinic of Pediatric Rheumatology, Zeynep Kamil Women and Children’s Diseases Training and Research Hospital, Istanbul, Turkey

    Mustafa Çakan

  14. Clinic of Pediatric Rheumatology, Ankara City Hospital, Ankara, Turkey

    Elif Çelikel, Zahide Ekici Tekin, Vildan Güngörer & Merve Cansu Polat

  15. Clinic of Pediatric Rheumatology, Acıbadem Healthcare Group, Istanbul, Turkey

    Ferhat Demir

  16. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Eskişehir Osmangazi University, Eskisehir, Turkey

    Selcan Demir

  17. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Çukurova University, Adana, Turkey

    Rabia Miray Kışla Ekinci

  18. Clinic of Pediatric Rheumatology, Bursa City Hospital, Bursa, Turkey

    Tuba Kurt

  19. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Sümeyra Özdemir Çiçek

  20. Clinic of Pediatric Rheumatology, Göztepe Prof. Dr. Süleyman Yalçın City Hospital, Istanbul, Turkey

    Kübra Öztürk

  21. Clinic of Pediatric Rheumatology, Ankara Training and Research Hospital, Ankara, Turkey

    Müge Sezer

  22. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey

    Hafize Emine Sönmez

  23. Clinic of Pediatric Rheumatology, Eskişehir City Hospital, Eskisehir, Turkey

    Sema Nur Taşkın

  24. Department of Pediatrics, Division of Pediatric Rheumatology, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Serkan Türkuçar

  25. Clinic of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey

    Betül Sözeri

Authors
  1. Emine Nur Sunar Yayla
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  2. Deniz Gezgin Yıldırım
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  3. Hatice Adıgüzel Dündar
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  4. Amra Adrovic
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  5. Elifsu Gözde Akbörü
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  6. Nuray Aktay Ayaz
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  7. Emil Aliyev
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  8. Pınar Özge Avar Aydın
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  9. Fatma Aydın
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  10. Özge Baba
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  11. Esra Bağlan
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  12. Balahan Bora Makay
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  13. Burcu Bozkaya Yücel
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  14. Mustafa Çakan
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  15. Elif Çelikel
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  16. Ferhat Demir
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  17. Selcan Demir
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  18. Fatma Gül Demirkan
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  19. Zahide Ekici Tekin
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  20. Pelin Esmeray Şenol
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  21. Vefa Guliyeva
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  22. Vildan Güngörer
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  23. Rana İşgüder
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  24. Mukaddes Kalyoncu
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  25. Şerife Gül Karadağ
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  26. Hakan Kısaoğlu
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  27. Rabia Miray Kışla Ekinci
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  28. Zehra Kızıldağ
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  29. Tuba Kurt
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  30. Semanur Özdel
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  31. Sümeyra Özdemir Çiçek
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  32. Kübra Öztürk
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  33. Merve Cansu Polat
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  34. Müge Sezer
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  35. Hafize Emine Sönmez
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  36. Betül Sözeri
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  37. Seher Şener
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  38. Sema Nur Taşkın
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  39. Serkan Türkuçar
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  40. Erbil Ünsal
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  41. Çisem Yıldız
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  42. Sevcan A. Bakkaloğlu
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Contributions

ENSY: Conceptualization (supporting), methodology, investigation (lead), and writing—original draft preparation (lead), DGY: Project administration, supervision (supporting), and writing—review and editing (supporting), HAD: Survey partipication and review, AA: Survey partipication and review, EGA: Survey partipication and review, NAA: Survey partipication and review, EA: Survey partipication and review, PÖAA: Survey partipication and review, FA: Survey partipication and review, ÖB: Survey partipication and review, EB: Survey partipication and review, BBM: Survey partipication and review, BBY: Survey partipication and review, MÇ: Survey partipication and review, EÇ: Survey partipication and review, FD: Survey partipication and review, SD: Survey partipication and review, FGD: Survey partipication and review, ZET: Survey partipication and review, PEŞ: Survey partipication and review, VG: Survey partipication and review, VG: Survey partipication and review, Rİ: Survey partipication and review, MK: Survey partipication and review, ŞGK: Survey partipication and review, HK: Survey partipication and review, MKE: Survey partipication and review, ZK: Survey partipication and review, TK: Survey partipication and review, SÖ: Survey partipication and review, SÖÇ: Survey partipication and review, KÖ: Survey partipication and review, MCP: Survey partipication and review, MS: Survey partipication and review, HES: Survey partipication and review, BS: Survey partipication and review, SŞ: Survey partipication and review, SNT: Survey partipication and review, ST: Survey partipication and review, EÜ: Survey partipication and review, ÇY: Survey partipication and review, SAB: Conceptualization (lead), supervision (lead) and writing—review and editing (lead).

Corresponding author

Correspondence to Emine Nur Sunar Yayla.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

The present study was approved by the local ethics committee of the Gazi University Medical Faculty (Decision no: E-77082166–604.01.02–559205 dated 12.01.2023).

Consent to participate

All participants consented to participate in the survey study.

Additional information

Communicated by Tobias Tenenbaum

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Sunar Yayla, E.N., Gezgin Yıldırım, D., Adıgüzel Dündar, H. et al. Evaluation of pediatric rheumatologists’ approach to rituximab use: a questionnaire study. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05654-9

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  • DOI: https://doi.org/10.1007/s00431-024-05654-9

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