nach oben

Erschienen in:

17.09.2021 | Original Article

The effectiveness of tocilizumab in treating refractory adult-onset Still’s disease with dichotomous phenotypes: IL-18 is a potential predictor of therapeutic response

verfasst von: Kuo-Tung Tang, Chia-Wei Hsieh, Hsin-Hua Chen, Yi-Ming Chen, Shih-Hsin Chang, Po-Hao Huang, Joung-Liang Lan, Der-Yuan Chen

Erschienen in: Clinical Rheumatology | Ausgabe 2/2022

Einloggen, um Zugang zu erhalten

Abstract

Objective

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration.

Methods

This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method.

Results

Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28 < 2.6) at weeks 12, 24, 36, and 48, respectively, among articular subtype patients. The systemic activity scores and inflammatory parameters were significantly decreased after 12-week TCZ therapy, and TCZ could significantly reduce corticosteroid dose in AOSD patients. Multivariate analysis reveals that baseline IL-18 level is a significant predictor of poor therapeutic response at week 24 (odds ratio 7.86, p < 0.05).

Conclusion

AOSD patients refractory to high-dose corticosteroids and methotrexate may respond well to TCZ treatment with a steroid-sparing effect and an acceptable safety. A high baseline IL-18 level may be a predictor of poor therapeutic response.

Key Points

• Tocilizumab may be effective and well-tolerated in refractory AOSD patients regardless of disease subtypes.

• High plasma levels of IL-18 may predict poor response to tocilizumab in AOSD patients.

Ohta A, Yamaguchi M, Kaneoka H, Nagayoshi T, Hiida M (1987) Adult Still’s disease: review of 228 cases from the literature. J Rheumatol 14(6):1139–1146PubMed

Kadavath S, Efthimiou P (2015) Adult-onset Still’s disease-pathogenesis, clinical manifestations, and new treatment options. Ann Med 47(1):6–14. https://doi.org/10.3109/07853890.2014.971052CrossRefPubMed

Lenert A, Yao Q (2016) Macrophage activation syndrome complicating adult onset Still’s disease: a single center case series and comparison with literature. Semin Arthritis Rheum 45(6):711–716. https://doi.org/10.1016/j.semarthrit.2015.11.002CrossRefPubMed

Yoo DH (2017) Treatment of adult-onset Still’s disease: up to date. Expert Rev Clin Immunol 13(9):849–866. https://doi.org/10.1080/1744666X.2017.1332994CrossRefPubMed

Castaneda S, Blanco R, Gonzalez-Gay MA (2016) Adult-onset Still’s disease: advances in the treatment. Best Pract Res Clin Rheumatol 30(2):222–238. https://doi.org/10.1016/j.berh.2016.08.003CrossRefPubMed

Kalyoncu U, Solmaz D, Emmungil H et al (2016) Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still’s disease: data from a large multicenter cohort. J Autoimmun 69:59–63. https://doi.org/10.1016/j.jaut.2016.02.010CrossRefPubMed

Choi JH, Suh CH, Lee YM et al (2003) Serum cytokine profiles in patients with adult onset Still’s disease. J Rheumatol 30(11):2422–2427PubMed

Kawaguchi Y, Terajima H, Harigai M, Hara M, Kamatani N (2001) Interleukin-18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still’s disease. Arthritis Rheum 44(7):1716–1717. https://doi.org/10.1002/1529-0131(200107)44:7%3c1716::AID-ART298%3e3.0.CO;2-ICrossRefPubMed

Chen DY, Chen YM, Lan JL, Lin CC, Chen HH, Hsieh CW (2010) Potential role of Th17 cells in the pathogenesis of adult-onset Still’s disease. Rheumatology (Oxford) 49(12):2305–2312. https://doi.org/10.1093/rheumatology/keq284CrossRef

10.

Hsieh CW, Chen YM, Lin CC et al (2017) Elevated expression of the NLRP3 inflammasome and its correlation with disease activity in adult-onset Still disease. J Rheumatol 44(8):1142–1150. https://doi.org/10.3899/jrheum.161354CrossRefPubMed

11.

Feist E, Mitrovic S, Fautrel B (2018) Mechanisms, biomarkers and targets for adult-onset Still’s disease. Nat Rev Rheumatol 14(10):603–618. https://doi.org/10.1038/s41584-018-0081-xCrossRefPubMedPubMedCentral

12.

Inoue N, Shimizu M, Tsunoda S, Kawano M, Matsumura M, Yachie A (2016) Cytokine profile in adult-onset Still’s disease: comparison with systemic juvenile idiopathic arthritis. Clin Immunol 169:8–13. https://doi.org/10.1016/j.clim.2016.05.010CrossRefPubMed

13.

Sfriso P, Bindoli S, Galozzi P (2018) Adult-onset Still’s disease: molecular pathophysiology and therapeutic advances. Drugs 78(12):1187–1195. https://doi.org/10.1007/s40265-018-0956-9CrossRefPubMed

14.

Puechal X, DeBandt M, Berthelot JM et al (2011) Tocilizumab in refractory adult Still’s disease. Arthritis Care Res (Hoboken) 63(1):155–159. https://doi.org/10.1002/acr.20319CrossRef

15.

de Boysson H, Fevrier J, Nicolle A, Auzary C, Geffray L (2013) Tocilizumab in the treatment of the adult-onset Still’s disease: current clinical evidence. Clin Rheumatol 32(1):141–147. https://doi.org/10.1007/s10067-012-2105-2CrossRefPubMed

16.

Ortiz-Sanjuan F, Blanco R, Calvo-Rio V et al (2014) Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still’s disease: multicenter retrospective open-label study of thirty-four patients. Arthritis Rheumatol 66(6):1659–1665. https://doi.org/10.1002/art.38398CrossRefPubMed

17.

Nishina N, Kaneko Y, Kameda H, Takeuchi T (2015) The effect of tocilizumab on preventing relapses in adult-onset Still’s disease: a retrospective, single-center study. Mod Rheumatol 25(3):401–404. https://doi.org/10.3109/14397595.2014.973659CrossRefPubMed

18.

Bannai E, Yamashita H, Kaneko S et al (2016) Successful tocilizumab therapy in seven patients with refractory adult-onset Still’s disease. Mod Rheumatol 26(2):297–301. https://doi.org/10.3109/14397595.2014.899178CrossRefPubMed

19.

Song ST, Kim JJ, Lee S et al (2016) Efficacy of tocilizumab therapy in Korean patients with adult-onset Still’s disease: a multicentre retrospective study of 22 cases. Clin Exp Rheumatol 34(6 Suppl 102):S64–S71PubMed

20.

Li T, Gu L, Wang X et al (2017) A pilot study on tocilizumab for treating refractory adult-onset Still’s disease. Sci Rep 7(1):13477. https://doi.org/10.1038/s41598-017-13639-yCrossRefPubMedPubMedCentral

21.

Wang CY, Guo SH, Wang LP, Shen HL (2019) Refractory adult-onset Still disease treated by tocilizumab combined with methotrexate: a STROBE-compliant article. Medicine (Baltimore) 98(32):e16682. https://doi.org/10.1097/MD.0000000000016682CrossRef

22.

Castaneda S, Martinez-Quintanilla D, Martin-Varillas JL, Garcia-Castaneda N, Atienza-Mateo B, Gonzalez-Gay MA (2019) Tocilizumab for the treatment of adult-onset Still’s disease. Expert Opin Biol Ther 19(4):273–286. https://doi.org/10.1080/14712598.2019.1590334CrossRefPubMed

23.

Ma Y, Wu M, Zhang X et al (2018) Efficacy and safety of tocilizumab with inhibition of interleukin-6 in adult-onset Still’s disease: a meta-analysis. Mod Rheumatol 28(5):849–857. https://doi.org/10.1080/14397595.2017.1416924CrossRefPubMed

24.

Kaneko Y, Kameda H, Ikeda K et al (2018) Tocilizumab in patients with adult-onset Still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial. Ann Rheum Dis 77(12):1720–1729. https://doi.org/10.1136/annrheumdis-2018-213920CrossRefPubMed

25.

Franchini S, Dagna L, Salvo F, Aiello P, Baldissera E, Sabbadini MG (2010) Efficacy of traditional and biologic agents in different clinical phenotypes of adult-onset Still’s disease. Arthritis Rheum 62(8):2530–2535. https://doi.org/10.1002/art.27532CrossRefPubMed

26.

Maria AT, Le Quellec A, Jorgensen C, Touitou I, Riviere S, Guilpain P (2014) Adult onset Still’s disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions. Autoimmun Rev 13(11):1149–1159. https://doi.org/10.1016/j.autrev.2014.08.032CrossRefPubMed

27.

Vercruysse F, Barnetche T, Lazaro E et al (2019) Adult-onset Still’s disease biological treatment strategy may depend on the phenotypic dichotomy. Arthritis Res Ther 21(1):53. https://doi.org/10.1186/s13075-019-1838-6CrossRefPubMedPubMedCentral

28.

Yamaguchi M, Ohta A, Tsunematsu T et al (1992) Preliminary criteria for classification of adult Still’s disease. J Rheumatol 19(3):424–430PubMed

29.

Rau M, Schiller M, Krienke S, Heyder P, Lorenz H, Blank N (2010) Clinical manifestations but not cytokine profiles differentiate adult-onset Still’s disease and sepsis. J Rheumatol 37(11):2369–2376. https://doi.org/10.3899/jrheum.100247CrossRefPubMed

30.

Prevoo ML, van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48. https://doi.org/10.1002/art.1780380107CrossRefPubMed

31.

Smolen JS, Aletaha D, Bijlsma JW et al (2010) Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 69(4):631–637. https://doi.org/10.1136/ard.2009.123919CrossRefPubMed

32.

CTEP cancer therapy evaluation program (2017) Common Terminology Criteria for Adverse Events (CTCAE) versions 5.0. National Cancer Institute. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50. Accessed 17 August 2021

33.

Cipriani P, Ruscitti P, Carubbi F et al (2014) Tocilizumab for the treatment of adult-onset Still’s disease: results from a case series. Clin Rheumatol 33(1):49–55. https://doi.org/10.1007/s10067-013-2381-5CrossRefPubMed

34.

Yoshida Y, Sakamoto M, Yokota K, Sato K, Mimura T (2011) Tocilizumab improved both clinical and laboratory manifestations except for interleukin-18 in a case of multiple drug-resistant adult-onset Still’s disease. Intern Med 50(16):1757–1760. https://doi.org/10.2169/internalmedicine.50.4771CrossRefPubMed

35.

Kir S, Ozgen M, Zontul S (2021) Adult-onset Still’s disease and treatment results with tocilizumab. Int J Clin Pract 75(3):e13936. https://doi.org/10.1111/ijcp.13936CrossRefPubMed

36.

Mercan R, Bitik B, Tufan A et al (2016) The association between neutrophil/lymphocyte ratio and disease activity in rheumatoid arthritis and ankylosing spondylitis. J Clin Lab Anal 30(5):597–601. https://doi.org/10.1002/jcla.21908CrossRefPubMed

37.

Seo JY, Suh CH, Jung JY, Kim AR, Yang JW, Kim HA (2017) The neutrophil-to-lymphocyte ratio could be a good diagnostic marker and predictor of relapse in patients with adult-onset Still’s disease: a STROBE-compliant retrospective observational analysis. Medicine (Baltimore) 96(29):e7546. https://doi.org/10.1097/MD.0000000000007546CrossRef

38.

Zhou S, Qiao J, Bai J, Wu Y, Fang H (2018) Biological therapy of traditional therapy-resistant adult-onset Still’s disease: an evidence-based review. Ther Clin Risk Manag 14:167–171. https://doi.org/10.2147/TCRM.S155488CrossRefPubMedPubMedCentral

39.

Ortiz-Sanjuan F, Blanco R, Riancho-Zarrabeitia L et al (2015) Efficacy of anakinra in refractory adult-onset Still’s disease: multicenter study of 41 patients and literature review. Medicine (Baltimore) 94(39):e1554. https://doi.org/10.1097/MD.0000000000001554CrossRef

40.

Yoo DH (2019) Biologics for the treatment of adult-onset Still’s disease. Expert Opin Biol Ther 19(11):1173–1190. https://doi.org/10.1080/14712598.2019.1652591CrossRefPubMed

41.

Ichida H, Kawaguchi Y, Sugiura T et al (2014) Clinical manifestations of adult-onset Still’s disease presenting with erosive arthritis: association with low levels of ferritin and interleukin-18. Arthritis Care Res (Hoboken) 66(4):642–646. https://doi.org/10.1002/acr.22194CrossRef

42.

Nam SW, Kang SM, Lee JH, Yoo DH (2021) Different features of interleukin-37 and interleukin-18 as disease activity markers of adult-onset Still’s disease. J Clin Med 10(5):910. https://doi.org/10.3390/jcm10050910CrossRefPubMedPubMedCentral

43.

Jung KH, Kim JJ, Lee JS et al (2014) Interleukin-18 as an efficient marker for remission and follow-up in patients with inactive adult-onset Still’s disease. Scand J Rheumatol 43(2):162–169. https://doi.org/10.3109/03009742.2013.824023CrossRefPubMed

44.

Tsuchida Y, Sumitomo S, Shoda H, Kubo K, Fujio K, Yamamoto K (2017) Macrophage activation syndrome associated with tocilizumab treatment in adult-onset Still’s disease. Mod Rheumatol 27(3):556–557. https://doi.org/10.1080/14397595.2016.1221875CrossRefPubMed

45.

Kobayashi M, Takahashi Y, Yamashita H, Kaneko H, Mimori A (2011) Benefit and a possible risk of tocilizumab therapy for adult-onset Still’s disease accompanied by macrophage-activation syndrome. Mod Rheumatol 21(1):92–96. https://doi.org/10.1007/s10165-010-0348-9CrossRefPubMed

46.

Wang R, Li T, Ye S et al (2020) Macrophage activation syndrome associated with adult-onset Still’s disease: a multicenter retrospective analysis. Clin Rheumatol 39(8):2379–2386. https://doi.org/10.1007/s10067-020-04949-0CrossRefPubMed

47.

Yamabe T, Ohmura SI, Uehara K, Naniwa T (2021) Macrophage activation syndrome in patients with adult-onset Still’s disease under tocilizumab treatment: a single-center observational study. Mod Rheumatol:1–8. https://doi.org/10.1080/14397595.2021.1899565

48.

Ruscitti P, Iacono D, Ciccia F et al (2018) Macrophage activation syndrome in patients affected by adult-onset Still disease: analysis of survival rates and predictive factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort. J Rheumatol 45(6):864–872. https://doi.org/10.3899/jrheum.170955CrossRefPubMed

Titel: The effectiveness of tocilizumab in treating refractory adult-onset Still’s disease with dichotomous phenotypes: IL-18 is a potential predictor of therapeutic response
verfasst von: Kuo-Tung Tang
Chia-Wei Hsieh
Hsin-Hua Chen
Yi-Ming Chen
Shih-Hsin Chang
Po-Hao Huang
Joung-Liang Lan
Der-Yuan Chen
Publikationsdatum: 17.09.2021
Verlag: Springer International Publishing
Erschienen in: Clinical Rheumatology / Ausgabe 2/2022
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-021-05921-2

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2022

Differentiation of idiopathic pulmonary hemosiderosis from rheumatologic and autoimmune diseases causing diffuse alveolar hemorrhage: establishing a diagnostic approach

Association of interleukin-6 promoter polymorphism with rheumatoid arthritis: a meta-analysis with trial sequential analysis

Association of quantitative computed tomography ındices with lung function and extent of pulmonary fibrosis in patients with systemic sclerosis

Association between biopsies for anti-neutrophil cytoplasmic antibody-associated vasculitis and prognosis: a retrospective cohort study

Three-dimensional ultrasonographic imaging of Mikulicz’s disease