Skip to main content
SpringerLink
Log in

Etanercept therapy in Behçet’s disease

The tight control strategy in refractory disease

Etanercepttherapie bei M. Behçet

Engmaschige Kontrolle bei therapierefraktärer Erkrankung

  • Originalien
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Abstract

Study objective

The goal of the present study was to investigate patient outcome when using the TNF receptor fusion protein etanercept in addition to conventional immunosuppressive drugs in ameliorating disease intensity and reducing relapses in refractory Behçet’s disease (BD).

Patients and methods

A single center, prospective study was conducted over 1 year. A total of 15 patients with the established diagnosis of BS were enrolled (mean age: 36.5 ± 6.75 years, mean disease duration: 3.86 ± 1.30 years). Clinical features were classified as refractory if the patients failed to achieve the desired response within 6 months of immunosuppressive and oral glucocorticoid therapy or flare of lesions developed while on the maximum tolerable doses of these drugs. The study included 2 patients who were on previous infliximab therapy for refractory disease. Inflammatory biomarkers (ESR and CRP) were investigated.

Results

Baseline clinical features in the study prior to inclusion showed recurrent oro-genital ulcers were observed in 100 % of patients, the pathergy test was positive in 17.6 %, ocular involvement was observed in 86.7 %, and acne lesions were recorded in 73.3 %. The following values were also recorded: mean ESR 22 ± 16.97 mm/h, mean CRP level 6.87 ± 4.44 mg/l, mean visual analog score 5.46 ± 1.55, and mean patient global score 5.13 ± 1.30. At the beginning of the study, all patients were on oral prednisolone (mean dose: 20.16 ± 11.81 mg/day), azathioprine (mean dose: 126.66 ± 25.81 mg/day), and oral colchicine (mean dose: 1.08 ± 0.10 mg/day), then etanercept was added at a regular weekly dose of 50 mg subcutaneously for 1 year. By 8 weeks, 100 % of the patients achieve the primary endpoint, which included clinical resolution of refractory mucocutaneous, joint, and active ocular lesions with normalization of the acute phase symptoms.

Conclusion

Patients with refractory BD who received a 12-month treatment with etanercept in addition to conventional immunosuppressive therapy achieved a good therapeutic response with successful reduction of oral prednisolone to a mean dose of 6.66 ± 2.24 mg/day. No serious infections or drug-related adverse events reported.

Zusammenfassung

Ziel der Studie

Ziel der Studie war es, den Erkrankungsverlauf zu untersuchen, wenn das TNF-Rezeptor-Fusionsprotein Etanercept zusätzlich zu herkömmlichen Immunsuppressiva zur Verminderung der Krankheitsintensität und von Rezidiven bei therapierefraktärem M. Behçet eingesetzt wurde.

Patienten und Methoden

Für ein Jahr wurde eine prospektive Einzelzentrumstudie durchgeführt. Insgesamt 15 Patienten mit gesicherter Diagnose eines M. Behçet wurden in die Studie aufgenommen (Durchschnittsalter: 36,5 ± 6,75 Jahre, mittlere Krankheitsdauer: 3,86 ± 1,30 Jahre). Nach den klinischen Symptomen wurde der Fall als therapierefraktär gewertet, wenn innerhalb von 6 Monaten Behandlung mit Immunsuppressiva und oralen Glukokortikoiden keine Therapieantwort oder ein Wiederauftreten von Läsionen während der Gabe der maximal tolerierbaren Dosen dieser Pharmaka eintrat. An der Studie nahmen auch 2 Patienten teil, die wegen therapierefraktärer Erkrankung zuvor mit Infliximab behandelt worden waren. Es wurden Biomarker für entzündliche Prozesse (BSG und CRP) bestimmt.

Ergebnisse

Vor Aufnahme in die Studie wurden bei 100 % der Patienten rezidivierende orogenitale Ulzera festgestellt, der Pathergietest war in 17,6 % der Fälle positiv, eine Augenbeteiligung bestand bei 86,7 % und Akneläsionen bei 73,3 %. Folgende Durchschnittswerte wurden ebenfalls dokumentiert: BSG: 22 ± 16,97 mm/h, CRP-Wert: 6,87 ± 4,44 mg/l, Wert auf der visuellen Analogskala: 5,46 ± 1,55 und Patient Global Score: 5,13 ± 1,30. Zu Beginn der Studie standen alle Patienten unter Gabe von Prednisolon oral (Durchschnittsdosis: 20,16 ± 11,81 mg/Tag), Azathioprin (Durchschnittsdosis: 126,66 ± 25,81 mg/Tag) und Colchicin oral (Durchschnittsdosis: 1,08 ± 0,10 mg/Tag), dann wurde zusätzlich Etanercept in einer regelmäßigen wöchentlichen Dosis von 50 mg subkutan für ein Jahr gegeben. Nach 8 Wochen erreichten 100 % der Patienten den primären Endpunkt, zu dem die klinische Heilung therapierefraktärer mukokutaner, Gelenk- und aktiver Augenläsionen mit Normalisierung der Symptome der Akutphase gehörte.

Schlussfolgerung

Patienten mit therapierefraktärem M. Behçet, die eine 12-monatige Behandlung mit Etanercept zusätzlich zur herkömmlichen Immunsuppressivatherapie erhielten, erzielten eine gute Therapieantwort mit erfolgreicher Senkung der Gabe von Prednisolon oral auf eine Durchschnittsdosis von 6,66 ± 2,24 mg/Tag. Es wurden weder schwere Infektionen noch medikamentenbedingte unerwünschte Ereignisse dokumentiert.

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

Similar content being viewed by others

References

  1. Gulli S, Arrigo C, Bocchino L et al (2003) Remission of Behcet’s disease with anti-tumor necrosis factor monoclonal antibody therapy: a case report. BMC Musculoskelet Disord 4:19

    Article  PubMed Central  PubMed  Google Scholar 

  2. Sakane T, Takeno M, Suzuki N et al (1999) Behcet’s disease. N Engl J Med 341:1284–1291

    Article  CAS  PubMed  Google Scholar 

  3. Hamzaoui K, Hamzaoui A, Guemira F et al (2002) Cytokine profile in Behcet’s disease patients. Relationship with disease activity. Scand J Rheumatol 31:205–210

    Article  PubMed  Google Scholar 

  4. Mantas C, Direskeneli H, Oz D et al (2000) IL-8 producing cells in patients with Behcet’s disease. Clin Exp Rheumatol 18:249–251

    CAS  PubMed  Google Scholar 

  5. Kaneko S, Suzuki N, Yamashita N et al (1997) Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behcet’s disease (BD) in Japan. Clin Exp Immunol 108:204–212

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Witowski J, Pawlaczyk K, Breborowicz A et al (2000) IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells. J Immunol 165:5814–5821

    Article  CAS  PubMed  Google Scholar 

  7. Turan B, Gallati H, Erdi H et al (1997) Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Behcet’s disease: soluble TNFR-75 as a biologic marker of disease activity. J Rheumatol 24:128–132

    CAS  PubMed  Google Scholar 

  8. Gul A (2001) Behcet’s disease: an update on the pathogenesis. Clin Exp Rheumatol 19(Suppl):S6–S12

    CAS  PubMed  Google Scholar 

  9. Yamashita N, Kaneoka H, Kaneko S et al (1997) Role of gammadelta T lymphocytes in the development of Behçet’s disease. Clin Exp Immunol 107(2):241–247

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Emmi L, Brugnolo F, Salvati G et al (1995) Immunopathological aspects of Behcet’s disease. Clin Exp Rheumatol 13:687–691

    CAS  PubMed  Google Scholar 

  11. Maini R, St Clair EW, Breedveld F et al (1999) Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatic arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet 354:1932–1939

    Article  CAS  PubMed  Google Scholar 

  12. Kaklamani VG, Kaklamanis PG (2001) Treatment of Behcet’s disease: an update. Semin Arthritis Rheum 30:299–312

    Article  CAS  PubMed  Google Scholar 

  13. Sfikakis PP, Theodossiadis PG, Katsiari CG et al (2002) Behcet’s disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis 61(Suppl II):S51–S53

    Google Scholar 

  14. Goossens PH, Verburg RJ, Breedveld FC (2001) Remission of Behcet’s syndrome with tumour necrosis factor a blocking therapy. Ann Rheum Dis 60:637

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Imrie FR, Dick AD (2007) Biologics in the treatment of uveitis. Curr Opin Ophthalmol 18:481–486

    Article  PubMed  Google Scholar 

  16. n A (1990) Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease. Lancet 335:1078–1080

    Google Scholar 

  17. Luqmani RA, Bacon PA, Moots RJ et al (1994) Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 87(11):671–678

    CAS  PubMed  Google Scholar 

  18. Ohno S, Ohguchi M, Hirose S et al (1982) Close association of HLA-Bw51 with Behcet’s disease. Arch Ophthalmol 100:1455–1458

    Article  CAS  PubMed  Google Scholar 

  19. Bawazeer A, Raffa LH, Nizamuddin SH (2010) Clinical experience with adalimumab in the treatment of ocular Behçet disease. Ocul Immunol Inflamm 18(3):226–232

    Article  CAS  PubMed  Google Scholar 

  20. Alokaily F, Alsaleh S, Al-Balawi M et al (2010) Efficacy of infliximab on the acute attack of uveitis. Saudi Med J 31(1):82–85

    PubMed  Google Scholar 

  21. Arida A, Fragiadaki K, Giavri E et al (2011) Anti-TNF agents for Behçet’s disease: analysis of published data on 369 patients. Sem Arthritis Rheum 41:61

    Article  CAS  Google Scholar 

  22. Melikoglu M, Fresko I, Mat C et al (2005) Short-term trial of etanercept in Behçet’s disease: a double blind, placebo controlled study. J Rheumatol 32(1):98–105

    CAS  PubMed  Google Scholar 

  23. Tabbara KF, Al-Hemidan AI (2008) Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet disease. Am J Ophthalmol 146(6):845–850

    Article  CAS  PubMed  Google Scholar 

  24. Al-Rayes H, Al-Swailem R, Al-Balawi M et al (2008) Safety and efficacy of infliximab therapy in active Behcet’s uveitis: an open-label trial. Rheumatol Int 29(1):53–57

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with ethical guidelines

Conflict of interest. R.H.A. Mohammed states that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Author information

Authors and Affiliations

  1. Rheumatology and Rehabilitation, Kasr Aleini school of Medicine, Cairo University Hospitals, Kasr Aleini Str., Garden City, Cairo, Egypt

    R.H.A. Mohammed MD, PhD

  2. Rheumatology Section/Internal Medicine Department, Alhada Armed forces Hospital, Alhada, KSA

    R.H.A. Mohammed MD, PhD

Authors
  1. R.H.A. Mohammed MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R.H.A. Mohammed MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mohammed, R. Etanercept therapy in Behçet’s disease. Z. Rheumatol. 73, 650–656 (2014). https://doi.org/10.1007/s00393-013-1307-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-013-1307-6

Keywords

Schlüsselwörter

Search

Navigation