Biologic Agents in Behçet’s Disease: Our Experience and Review of the Literature

Nesibe Karahan Yeşil¹, Hatice Şahin², Hatice Işık³, Zuhal Örnek⁴, Serpil Yazgan⁵, Adem Tok⁶, Yunus Emre Yandı⁷, Metin Işık^8*, İsmail Doğan⁹

¹Department of Rheumatology, Ankara Research and Education Hospital, Ankara, Turkey.
²Department of Internal Medicine, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
³Department of Obstetrics and Gynecology, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
⁴Department of Pediatric Disaease, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
⁵Department of Ophtalmology, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
⁶Department of Urology, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
⁷Division of Biochemistry, Department of Medical Services and Techniques, Health Sciences, Vocational School, Bülent Ecevit University, Zonguldak, Turkey.
⁸Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
⁹Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hitit University, Çorum, Turkey.

DOI: 10.4236/ojra.2015.54016                

Abstract

Behcet’s disease (BD) is a large vessel vasculitis with a wide range of clinical manifestations. Some of these manifestation may be life threatening and rapid suppression of the inflammation with effective immunosuppressive agent is crucial. There are traditional drugs with different response rates and all have efficacy on different manifestations of the disease. The most frightening manifestations of the disease are ocular, neurologic, intestinal and vascular types of involvement. Besides benign and easily treated manifestations there are also refractory cases with complicated involvement. The novel biologic agents have been used for these resistant patients and favorable response rates have been reported. In this review, we have shared our experience with biologic agents in BD and also reviewed the literature for the efficacy and safety for these novel agents for refractory patients.

Keywords

Behçet’s Disease, Novel Biologic Agents, Refractory Patients

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Arayssi, T. and Hamdan, A. (2004) New Insights into the Pathogenesis and Therapy of Behcet’s Disease. Current Opinion in Pharmacology, 4, 183-188. http://dx.doi.org/10.1016/j.coph.2003.10.009
[2]	Sakane, T., Takeno, M., Suzuki, N. and Inaba, G. (1990) Behcet’s Disease. New England Journal of Medicine, 341, 1284-1291. http://dx.doi.org/10.1056/NEJM199910213411707
[3]	Yurdakul, S., Mat, C., Tuzun, Y., Ozyazgan, Y., Hamuryudan, V., Uysal, O., et al. (2001) A Doubleblind Trial of Colchicine in Behcet’s Syndrome. Arthritis & Rheumatology, 44, 2686-2692. http://dx.doi.org/10.1002/1529-0131(200111)44:11<2686::AID-ART448>3.0.CO;2-H
[4]	Comarmond, C., Wechsler, B., Bodaghi, B., Cacoub, P. and Saadoun, D. (2014) Biotherapies in Behçet’s Disease. Autoimmunity Reviews, 13, 762-769. http://dx.doi.org/10.1016/j.autrev.2014.01.056
[5]	Mesquida, M., Molins, B., Llorenç, V., Hernández, M.V., Espinosa, G., Dick, A.D. and Adán, A. (2014) Current and Future Treatments for Behçet’s Uveitis: Road to Remission. International Ophthalmology, 34, 365-381. http://dx.doi.org/10.1007/s10792-013-9788-5
[6]	Fountain, E.M. and Dhurandhar, A. (2014) Neuro-Behçet’s Disease: An Unusual Cause of Headache. Journal of General Internal Medicine, 29, 956-960. http://dx.doi.org/10.1007/s11606-014-2781-5
[7]	Saip, S., Akman-Demir, G. and Siva, A. (2014) Neuro-Behçet Syndrome. Handbook of Clinical Neurology, 121, 1703- 1723. http://dx.doi.org/10.1016/B978-0-7020-4088-7.00110-3
[8]	Chin, A.B. and Kumar, A.S. (2015) Behcet Colitis. Clinics in Colon and Rectal Surgery, 28, 99-102. http://dx.doi.org/10.1055/s-0035-1547336
[9]	Kotter, I., Zierhut, M., Eckstein, A., Vonthein, R., Ness, T., Gunaydin, I., et al. (2003) Human Recombinant Interferon Alfa-2a for the Treatment of Behcet’s Disease with Sight Threatening Posterior or Panuveitis. British Journal of Ophthalmology, 87, 423-431. http://dx.doi.org/10.1136/bjo.87.4.423
[10]	Deuter, C.M., Zierhut, M., Möhle, A., Vonthein, R., Stöbiger, N. and Kötter, I. (2010) Long-Term Remission after Cessation of Interferon-α Treatment in Patients with Severe Uveitis Due to Behçet’s Disease. Arthritis & Rheumatology, 62, 2796-2805. http://dx.doi.org/10.1002/art.27581
[11]	Kotter, I., Gunaydin, I., Zierhut, M. and Stubiger, N. (2004) The Use of Interferon Alpha in Behcet Disease: Review of the Literature. Seminars in Arthritis and Rheumatism, 33, 320-335. http://dx.doi.org/10.1016/j.semarthrit.2003.09.010
[12]	Takeuchi, M., Kezuka, T., Sugita, S., Keino, H., Namba, K., Kaburaki, T., Maruyama, K., Nakai, K., Hijioka, K., Shibuya, E., Komae, K., Hori, J., Ohguro, N., Sonoda, K.H., Mizuki, N., Okada, A.A., Ishibashi, T., Goto, H. and Mochizuki, M. (2014) Evaluation of the Long-Term Efficacy and Safety of Infliximab Treatment for Uveitis in Behçet’s Disease: A Multicenter Study. Ophthalmology, 121, 1877-1884. http://dx.doi.org/10.1016/j.ophtha.2014.04.042
[13]	Keino, H., Okada, A.A., Watanabe, T. and Taki, W. (2014) Long-Term Efficacy of Infliximab on Background Vascular Leakage in Patients with Behçet’s Disease. Eye, 28, 1100-1106. http://dx.doi.org/10.1038/eye.2014.138
[14]	Kaburaki, T., Namba, K., Sonoda, K.H., Kezuka, T., Keino, H., Fukuhara, T., Kamoi, K., Nakai, K., Mizuki, N. and Ohguro, N., Ocular Behçet Disease Research Group of Japan (2014) Behçet’s Disease Ocular Attack Score 24: Evaluation of Ocular Disease Activity before and after Initiation of Infliximab. Japanese Journal of Ophthalmology, 58, 120- 130. http://dx.doi.org/10.1007/s10384-013-0294-0
[15]	Okada, A.A., Goto, H., Ohno, S. and Mochizuki, M., Ocular Behçet’s Disease Research Group of Japan (2012) Multicenter Study of Infliximab for Refractory Uveoretinitis in Behçet Disease. Archives of Ophthalmology, 130, 592-598. http://dx.doi.org/10.1001/archophthalmol.2011.2698
[16]	Perra, D., Alba, M.A., Callejas, J.L., Mesquida, M., Ríos-Fernández, R., Adán, A., Ortego, N., Cervera, R. and Espinosa, G. (2012) Adalimumab for the Treatment of Behcet’s Disease: Experience in 19 Patients. Rheumatology, 51, 1825-1831. http://dx.doi.org/10.1093/rheumatology/kes130
[17]	Arida, A., Fragiadaki, K., Giavri, E. and Sfikakis, P.P. (2011) Anti-TNF Agents for Behçet’s Disease: Analysis of Published Data on 369 Patients. Seminars in Arthritis and Rheumatism, 41, 61-70. http://dx.doi.org/10.1016/j.semarthrit.2010.09.002
[18]	Levy-Clarke, G., Jabs, D.A., Read, R.W., Rosenbaum, J.T., Vitale, A. and Van Gelder, R.N. (2014) Expert Panel Recommendations for the Use of Anti-Tumor Necrosis Factor Biologic Agents in Patients with Ocular Inflammatory Disorders. Ophthalmology, 121, 785-796.e3. http://dx.doi.org/10.1016/j.ophtha.2013.09.048
[19]	Urbaniak, P., Hasler, P. and Kretzschmar, S. (2012) Refractory Neuro-Behçet Treated by Tocilizumab: A Case Report. Clinical and Experimental Rheumatology, 30, S73-S75.
[20]	Haghighi, A.B., Safari, A., Nazarinia, M.A., Habibagahi, Z. and Shenavandeh, S. (2011) Infliximab for Patients with Neuro-Behcet’s Disease: Case Series and Literature Review. Clinical Rheumatology, 30, 1007-1012. http://dx.doi.org/10.1007/s10067-011-1726-1
[21]	Kanemaru, H., Makino, T., Jinnin, M., Yonemitsu, A., Makino, K. and Ihn, H. (2013) Case of Neuro-Behçet’s Disease Successfully Maintained a Remission Using Infliximab for 2 Years. The Journal of Dermatology, 40, 632-634. http://dx.doi.org/10.1111/1346-8138.12203
[22]	Hirohata, S. and Kikuchi, H. (2012) Changes in Biomarkers Focused on Differences in Disease Course or Treatment in Patients with Neuro-Behçet’s Disease. Internal Medicine, 51, 3359-3365. http://dx.doi.org/10.2169/internalmedicine.51.8583
[23]	Shapiro, L.S., Farrell, J. and Haghighi, A.B. (2012) Tocilizumab Treatment for Neuro-Behcet’s Disease, the First Report. Clinical Neurology and Neurosurgery, 114, 297-298. http://dx.doi.org/10.1016/j.clineuro.2011.10.024
[24]	Hatemi, G., Silman, A., Bang, D., Bodaghi, B., Chamberlain, A.M., Gul, A., Houman, M.H., Kötter, I., Olivieri, I., Salvarani, C., Sfikakis, P.P., Siva, A., Stanford, M.R., Stübiger, N., Yurdakul, S. and Yazici, H., EULAR Expert Committee (2008) EULAR Recommendations for the Management of Behçet Disease. Annals of the Rheumatic Diseases, 67, 1656-1662. http://dx.doi.org/10.1136/ard.2007.080432
[25]	Sfikakis, P.P., Markomichelakis, N., Alpsoy, E., Assaad-Khalil, S., Bodaghi, B., Gul, A., Ohno, S., Pipitone, N., Schirmer, M., Stanford, M., Wechsler, B., Zouboulis, C., Kaklamanis, P. and Yazici, H. (2007) Anti-TNF Therapy in the Management of Behcet’s Disease—Review and Basis for Recommendations. Rheumatology, 46, 736-741. http://dx.doi.org/10.1093/rheumatology/kem034
[26]	Travis, S.P., Czajkowski, M., McGovern, D.P., Watson, R.G. and Bell, A.L. (2001) Treatment of Intestinal Behçet’s Syndrome with Chimeric Tumour Necrosis Factor Alpha Antibody. Gut, 49, 725-728. http://dx.doi.org/10.1136/gut.49.5.725
[27]	Hassard, P.V., Binder, S.W., Nelson, V. and Vasiliauskas, E.A. (2001) Anti-Tumor Necrosis Factor Monoclonal Antibody Therapy for Gastrointestinal Behçet’s Disease: A Case Report. Gastroenterology, 120, 995-999. http://dx.doi.org/10.1053/gast.2001.22556
[28]	Naganuma, M., Sakuraba, A., Hisamatsu, T., Ochiai, H., Hasegawa, H., Ogata, H., Iwao, Y. and Hibi, T. (2008) Efficacy of Infliximab for Induction and Maintenance of Remission in Intestinal Behçet’s Disease. Inflammatory Bowel Diseases, 14, 1259-1264. http://dx.doi.org/10.1002/ibd.20457
[29]	Iwata, S., Saito, K., Yamaoka, K., Tsujimura, S., Nawata, M., Suzuki, K. and Tanaka, Y. (2009) Effects of Anti-TNF- Alpha Antibody Infliximab in Refractory Entero-Behcet’s Disease. Rheumatology, 48, 1012-1013. http://dx.doi.org/10.1093/rheumatology/kep126
[30]	Kinoshita, H., Kunisaki, R., Yamamoto, H., Matsuda, R., Sasaki, T., Kimura, H., Tanaka, K., Naganuma, M. and Maeda, S. (2013) Efficacy of Infliximab in Patients with Intestinal Behçet’s Disease Refractory to Conventional Medication. Internal Medicine, 52, 1855-1862. http://dx.doi.org/10.2169/internalmedicine.52.0589
[31]	Lee, J.H., Cheon, J.H., Jeon, S.W., Ye, B.D., Yang, S.K., Kim, Y.H., Lee, K.M., Im, J.P., Kim, J.S., Lee, C.K., Kim, H.J., Kim, E.Y., Kim, K.O., Jang, B.I. and Kim, W.H. (2013) Efficacy of Infliximab in Intestinal Behçet’s Disease: A Korean Multicenter Retrospective Study. Inflammatory Bowel Diseases, 19, 1833-1838.
[32]	De Cassan, C., De Vroey, B., Dussault, C., Hachulla, E., Buche, S. and Colombel, J.F. (2011) Successful Treatment with Adalimumab in a Familial Case of Gastrointestinal Behcet’s Disease. Journal of Crohn’s and Colitis, 5, 364-368. http://dx.doi.org/10.1016/j.crohns.2011.03.006
[33]	Ariyachaipanich, A., Berkelhammer, C. and Nicola, H. (2009) Intestinal Behçet’s Disease: Maintenance of Remission with Adalimumab Monotherapy. Inflammatory Bowel Diseases, 15, 1769-1771. http://dx.doi.org/10.1002/ibd.20869
[34]	van Laar, J.A., Missotten, T., van Daele, P.L., Jamnitski, A., Baarsma, G.S. and van Hagen, P.M. (2007) Adalimumab: A New Modality for Behçet’s Disease? Annals of the Rheumatic Diseases, 66, 565-566. http://dx.doi.org/10.1136/ard.2006.064279
[35]	Shimizu, Y., Takeda, T., Matsumoto, R., Yoshida, K., Nakajima, J., Atarashi, T., Yanagisawa, H., Kikuchi, K. and Kikuchi, H. (2012) Clinical Efficacy of Adalimumab for a Postoperative Marginal Ulcer in Gastrointestinal Behçet Disease. Nihon Shokakibyo Gakkai Zasshi, 109, 774-780.
[36]	Sylwestrzak, G., Liu, J., Stephenson, J.J., Ruggieri, A.P. and De Vries, A. (2014) Considering Patient Preferences When Selecting Anti-Tumor Necrosis Factor Therapeutic Options. Am Health Drug Benefits, 7, 71-81.
[37]	Tanida, S., Inoue, N., Kobayashi, K., Naganuma, M., Hirai, F., Iizuka, B., Watanabe, K., Mitsuyama, K., Inoue, T., Ishigatsubo, Y., Suzuki, Y., Nagahori, M., Motoya, S., Nakamura, S., Arora, V., Robinson, A.M., Thakkar, R.B. and Hibi, T. (2015) Adalimumab for the Treatment of Japanese Patients with Intestinal Behçet’s Disease. Clinical Gastroenterology and Hepatology, 13, 940-948.e3. http://dx.doi.org/10.1016/j.cgh.2014.08.042
[38]	Schäfer, V.S. and Zwerina, J. (2012) Biologic Treatment of Large-Vessel Vasculitides. Current Opinion in Rheumatology, 24, 31-37. http://dx.doi.org/10.1097/BOR.0b013e32834dc392
[39]	Adler, S., Baumgartner, I. and Villiger, P.M. (2012) Behçet’s Disease: Successful Treatment with Infliximab in 7 Patients with Severe Vascular Manifestations. A Retrospective Analysis. Arthritis Care & Research, 64, 607-611. http://dx.doi.org/10.1002/acr.21557
[40]	Lee, S.W., Lee, S.Y., Kim, K.N., Jung, J.K. and Chung, W.T. (2010) Adalimumab Treatment for Life Threatening Pulmonary Artery Aneurysm in Behçet Disease: A Case Report. Clinical Rheumatology, 29, 91-93. http://dx.doi.org/10.1007/s10067-009-1272-2
[41]	Donghi, D. and Mainetti, C. (2010) Infliximab for the Treatment of Refractory Adamantiades-Behçet Disease with Articular, Intestinal, Cerebral and Ocular Involvement. Dermatology, 220, 282-286. http://dx.doi.org/10.1159/000277928