Skip to main content

Advertisement

SpringerLink
Log in

Rituximab or cyclosporin in refractory immune thrombocytopenia secondary to connective tissue diseases: a real-world observational retrospective study

  • Brief Report
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Immune thrombocytopenia (ITP) is a common complication of connective tissue diseases (CTD). However, refractory and recurrent cases are frequent, who often need intensive immunotherapy. In the real world to compare the efficacy and safety of two common options, rituximab (RTX) and cyclosporine (CsA), in patients with refractory CTD-ITP, we conducted this retrospective study. Inpatients diagnosed with CTD-ITP who experienced treatment failure with initial prednisone or other immunosuppressants and who subsequently received either RTX or CsA between 2013 and 2018 were identified. All the patients were followed up for at least 6 months. Remission was defined as sustained platelet count ≥ 50 × 10^9/L, where ≥ 100 × 10^9/L was considered complete remission and 50–100 × 10^9/L was considered partial remission. Propensity score weighting analysis was performed to balance the confounders as indication. A total of 83 patients with CTD-ITP were identified, of whom 43 had systemic lupus erythematosus, 24 had undifferentiated CTD, and 16 had primary Sjogren syndrome. The RTX group (n = 53) had a much higher remission rate than the CsA group (n = 30) after 3 months and throughout the following 3 months (3 m, 86.8% vs 63.6%, p = 0.025; 6 m, 81.8% vs 53.5%, p = 0.011). Binary logistic regression analysis confirmed that treatment with RTX predicted better outcome (OR 4.09, 1.42 ~ 11.79), while age > 50 (OR 0.31, 0.11 ~ 0.93) was a risk factor. Furthermore, we reinforced the conclusions by propensity score weighting analysis (RTX OR 4.89, 1.64 ~ 14.58; age > 50 OR 0.31, 0.12 ~ 0.83). In our real-world retrospective study, for patients with refractory CTD-ITP, RTX was superior to CsA in terms of the durable remission rate.

Key Points:

• Refractory cases are common in patients with immune thrombocytopenia secondary to connective tissue diseases (CTD-ITP), requiring intensive immunotherapy.

• Randomized controlled trials comparing rituximab and a traditional immunosuppressive agents (IS), such as cyclosporin, are lacking in these patients.

• Our real-word retrospective study indicated that rituximab was superior to cyclosporin in patients with refractory CTD-ITP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Liu Y, Chen S, Sun Y, Lin Q, Liao X, Zhang J, Luo J, Qian H, Duan L, Shi G (2016) Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: a retrospective study. Medicine 95(50):e5565. https://doi.org/10.1097/MD.0000000000005565

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Ozkan MC, Sahin F, Saydam G (2015) Immune thrombocytopenic purpura: new biological therapy of an old disease. Curr Med Chem 22(16):1956–1962

    Article  CAS  Google Scholar 

  3. Zhang W, Wang F, Wang H, Hua B, Feng X, Sun L (2018) Severe thrombocytopenia in connective tissue diseases: a single-center review of 131 cases. Clin Rheumatol 37(12):3337–3344. https://doi.org/10.1007/s10067-018-4312-y

    Article  PubMed  Google Scholar 

  4. Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115(2):168–186. https://doi.org/10.1182/blood-2009-06-225565

    Article  PubMed  CAS  Google Scholar 

  5. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA, American Society of H (2011) The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117(16):4190–4207. https://doi.org/10.1182/blood-2010-08-302984

    Article  PubMed  CAS  Google Scholar 

  6. Serris A, Amoura Z, Canoui-Poitrine F, Terrier B, Hachulla E, Costedoat-Chalumeau N, Papo T, Lambotte O, Saadoun D, Hie M, Blanche P, Lioger B, Gottenberg JE, Godeau B, Michel M (2018) Efficacy and safety of rituximab for systemic lupus erythematosus-associated immune cytopenias: a multicenter retrospective cohort study of 71 adults. Am J Hematol 93(3):424–429. https://doi.org/10.1002/ajh.24999

    Article  PubMed  CAS  Google Scholar 

  7. Kapoor R, Kumar R, Mahapatra M, Pati HP, Pramanik SK (2017) Low dose rituximab in chronic ITP: still an option in resource limited settings. Indian Journal of Hematology & Blood Transfusion 33(4):568–573. https://doi.org/10.1007/s12288-016-0764-x

    Article  Google Scholar 

  8. Hindilerden F, Yonal-Hindilerden I, Yenerel MN, Nalcaci M, Diz-Kucukkaya R (2017) Rituximab therapy in adults with refractory symptomatic immune thrombocytopenia: long-term follow-up of 15 cases. Turkish Journal of Haematology 34(1):72–80. https://doi.org/10.4274/tjh.2016.0086

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Jiang B, Li T, Guo L, Shen H, Ye S, Chen S (2015) Efficacy and safety of rituximab in systemic lupus Erythematosus and Sjogren syndrome patients with refractory thrombocytopenia: a retrospective study of 21 cases. Journal of Clinical Rheumatology 21(5):244–250. https://doi.org/10.1097/RHU.0000000000000273

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen H, Zheng W, Su J, Xu D, Wang Q, Leng X, Zhang W, Li M, Tang F, Zhang X, Zeng X, Zhao Y, Zhang F (2011) Low-dose rituximab therapy for refractory thrombocytopenia in patients with systemic lupus erythematosus--a prospective pilot study. Rheumatology 50(9):1640–1644. https://doi.org/10.1093/rheumatology/ker176

    Article  PubMed  CAS  Google Scholar 

  11. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS (2012) Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686. https://doi.org/10.1002/art.34473

    Article  PubMed  PubMed Central  Google Scholar 

  12. Garcia D, Erkan D (2018) Diagnosis and management of the antiphospholipid syndrome. N Engl J Med 379(13):1290. https://doi.org/10.1056/NEJMc1808253

    Article  PubMed  Google Scholar 

  13. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X, International Sjogren’s Syndrome Criteria Working G (2017) 2016 American College of Rheumatology/European League against rheumatism classification criteria for primary Sjogren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis & rheumatology 69(1):35–45. https://doi.org/10.1002/art.39859

    Article  Google Scholar 

  14. Mosca M, Tani C, Vagnani S, Carli L, Bombardieri S (2014) The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun 48-49:50–52. https://doi.org/10.1016/j.jaut.2014.01.019

    Article  PubMed  Google Scholar 

  15. Zhao L, Xu D, Qiao L, Zhang X (2016) Bone marrow megakaryocytes may predict therapeutic response of severe thrombocytopenia in patients with systemic lupus erythematosus. J Rheumatol 43(6):1038–1044. https://doi.org/10.3899/jrheum.150829

    Article  PubMed  Google Scholar 

  16. Mardjuadi A, Soedirman M, Utoyo B, Rasker JJ (2009) Prompt remission of severe SLE with only three doses of rituximab infusion and low dose steroid: the first case report from Indonesia. Clin Rheumatol 28(Suppl 1):S27–S30. https://doi.org/10.1007/s10067-008-1069-8

    Article  PubMed  Google Scholar 

  17. Zaja F, Vianelli N, Volpetti S, Battista ML, Defina M, Palmieri S, Bocchia M, Medeot M, De Luca S, Ferrara F, Isola M, Baccarani M, Fanin R (2010) Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol 85(4):329–334. https://doi.org/10.1111/j.1600-0609.2010.01486.x

    Article  PubMed  CAS  Google Scholar 

  18. Li Y, Wang YY, Fei HR, Wang L, Yuan CL (2015) Efficacy of low-dose rituximab in combination with recombinant human thrombopoietin in treating ITP. Eur Rev Med Pharmacol Sci 19(9):1583–1588

    PubMed  CAS  Google Scholar 

  19. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, Cervera R, Doria A, Gordon C, Govoni M, Houssiau F, Jayne D, Kouloumas M, Kuhn A, Larsen JL, Lerstrom K, Moroni G, Mosca M, Schneider M, Smolen JS, Svenungsson E, Tesar V, Tincani A, Troldborg A, van Vollenhoven R, Wenzel J, Bertsias G, Boumpas DT (2019) 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 78:736–745. https://doi.org/10.1136/annrheumdis-2019-215089

    Article  PubMed  CAS  Google Scholar 

  20. Palandri F, Catani L, Auteri G, Bartoletti D, Fatica S, Fusco A, Bacchi Reggiani ML, Cavo M, Vianelli N (2019) Understanding how older age drives decision-making and outcome in immune thrombocytopenia. A single centre study on 465 adult patients. Br J Haematol 184(3):424–430. https://doi.org/10.1111/bjh.15668

    Article  PubMed  CAS  Google Scholar 

  21. Marangon M, Vianelli N, Palandri F, Mazzucconi MG, Santoro C, Barcellini W, Fattizzo B, Volpetti S, Lucchini E, Polverelli N, Carpenedo M, Isola M, Fanin R, Zaja F (2017) Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response. Eur J Haematol 98(4):371–377. https://doi.org/10.1111/ejh.12839

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

Fangfang Sun has received funding from Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University (2016PWGZR03) and Health and Family Planning Commission of Shanghai Minhang District (2018MW54). Shuang Ye has received funding from Shanghai Shenkang Promoting Project (16CR1013A).

Author information

Author notes

  1. Fangfang Sun and Jie Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Jiang Yue Road 2000, Shanghai, 201112, China

    Fangfang Sun, Jie Chen, Wanlong Wu, Shikai Geng, WenWen Xu, Shuhui Sun, Zhiwei Chen, Liyang Gu, Xiaodong Wang, Ting Li & Shuang Ye

Authors
  1. Fangfang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wanlong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shikai Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. WenWen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuhui Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhiwei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liyang Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaodong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ting Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shuang Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors took part in revising the article and approved the final version to be published. S.Y., T.L., and X.W. contributed to the conception and design. W.W., S.G., W.X., and S.S. were responsible for collecting the data. F.S., J.C., Z.C., and L.G. performed the analysis and drafted the article. F.S. and J.C. contributed equally to this article.

Corresponding author

Correspondence to Shuang Ye.

Ethics declarations

Disclosures

None.

Ethics approval and consent to participate

The protocol of this study complied with the recommendations of the Declaration of Helsinki and was approved by the ethics committees of Ren Ji Hospital. An informed consent for off-label use of rituximab was obtained from all patients.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, F., Chen, J., Wu, W. et al. Rituximab or cyclosporin in refractory immune thrombocytopenia secondary to connective tissue diseases: a real-world observational retrospective study. Clin Rheumatol 39, 3099–3104 (2020). https://doi.org/10.1007/s10067-020-05152-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05152-x

Keywords

Search

Navigation