Erişkin Still Hastalığında İnterlökin-1 İnhibitörü Tedavisinin Etkinlik ve Yan Etkilerinin Değerlendirilmesi

Yıl 2024, Cilt: 50 Sayı: 3, 391 - 396, 12.01.2025

Tuğba Ocak , Burcu Yağız , Belkis Nihan Coskun , Yavuz Pehlivan , Hüseyin Ediz Dalkılıç

https://doi.org/10.32708/uutfd.1559614

Öz

Erişkin Still hastalığı (ESH) multigenik otoinflamatuar bir hastalıktır. İnterlökin (IL)-1 inhibitörleri tedaviye dirençli ESH’de kullanılabilir. Çalışmamızda ESH’de IL-1 inhibitörlerinin etkinlik ve yan etkileri ile ilgili gerçek yaşam deneyimimizi sunmayı amaçladık. Hastanemiz romatoloji kliniğinde Ocak 2016-Mart 2024 tarihleri arasında ESH tanısı ile takip edilen 24 hastanın dosyası retrospektif olarak incelendi. Anakinra alan 22 hasta ve kanakinumab alan 5 hasta mevcuttu. Kanakinumab alan hastalardan 3 tanesi daha önce anakinra tedavisi almıştı. Çalışmaya dahil edilen hastaların ortalama tanı yaşı 29,7 (16,5-75,3) yıldı. Hastaların 16’sı kadındı. Anakinra alan hastaların ortanca takip süresi 13,5 (0,8-92,5) ay saptandı. Hastaların anakinra başlangıç, 3. ay ve son vizitleri arasında ateş, boğaz ağrısı, döküntü, artrit, artralji, modifiye Pouchot skoru, ferritin, sedimentasyon ve C-reaktif protein parametrelerinde istatistiksel açıdan anlamlı fark mevcuttu (p<0,001, p<0,001, p<0,001, p<0,001, p=0,001, p<0,001, p<0,001, p<0,001 ve p<0,001, sırasıyla). Kanakinumab alan hastaların ortalama takip süresi 70,2±46,7 aydı. Kanakinumab başlangıcı, 3.ay ve son poliklinik vizitindeki döküntü, modifiye Pouchot skoru ve sedimentasyon değerleri arasında istatistiksel açıdan anlamlı fark saptandı (p=0,015, p=0,015 ve p=0,029, sırasıyla). Anakinra tedavisi ile 1 hastada alerjik cilt döküntüsü, 1 hastada tekrarlayan idrar yolu enfeksiyonu, 1 hastada lökopeni ve nötropeni saptandı. Kanakinumab tedavisi ile yan etki görülmedi. IL-1 inhibitörleri geleneksel tedaviye yanıt vermeyen ESH hastalarında ilk basamak biyolojik ajan olarak düşünülebilir.

Anahtar Kelimeler

Anakinra, Erişkin Still Hastalığı, Kanakinumab.

Evaluation of the Efficacy and Side Effects of Interleukin-1 Inhibitor Therapy in Adult Still's Disease

Öz

Adult Still's disease (ASD) is a multigenic autoinflammatory disease. Interleukin (IL)-1 inhibitors can be used in treatment-resistant ASD. We aimed to present our experience with the efficacy and side effects of IL-1 inhibitors in ASD. The records of 24 patients who were treated in the rheumatology clinic of our hospital between January 2016 and March 2024 with a diagnosis of ASD were retrospectively analyzed. There were 22 patients who received anakinra and 5 patients who received kanakinumab. Three of the patients receiving kanakinumab had previously been treated with anakinra. The mean age at diagnosis was 29.7 (16.5-75.3) years. Sixteen of the patients were female. The median follow-up time of patients who received anakinra was 13.5 (0.8-92.5) months. There were statistically significant differences in fever, sore throat, rash, arthritis, arthralgia, modified Pouchot score, ferritin, erythrocyte sedimentation rate (ESR) and C-reactive protein between baseline anakinra, month 3 and the last visit (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.001, p<0.001, p<0.001, p<0.001 and p<0.001, respectively). The mean follow-up time of patients receiving canakinumab was 70.2±46.7 months. There was a statistically significant difference between the rash, modified Pouchot score and ESR at baseline, month 3 and the last outpatient visit (p=0.015, p=0.015 and p=0.029, respectively). Allergic skin rash in 1 patient, recurrent urinary tract infections in 1 patient, leukopenia and neutropenia in 1 patient were observed with anakinra. No side effects were observed with kanakinumab. IL-1 inhibitors can be considered as first-line biologic treatment in patients with ASD who do not respond to conventional treatment.

Anahtar Kelimeler

Anakinra., Adult Still disease, Canakinumab

Kaynakça

• 1.Jamilloux Y, Gerfaud-Valentin M, Henry T, Sève P. Treatment of adult-onset Still's disease: a review. Ther Clin Risk Manag 2014;11:33-43. doi: 10.2147/TCRM.S64951
• 2.Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P. Adult-onset Still's disease. Autoimmun Rev 2014;13:708-22. doi: 10.1016/j.autrev.2014.01.058
• 3.Fujii T, Nojima T, Yasuoka H, et al. Cytokine and immunogenetic profiles in Japanese patients with adult Still's disease. Association with chronic articular disease. Rheumatology 2001;40:1398-404. doi: 10.1093/rheumatology/40.12.1398
• 4.Giampietro C, Fautrel B. Anti-Interleukin-1 Agents in Adult Onset Still's Disease. Int J Inflam 2012;2012:317820. doi: 10.1155/2012/317820
• 5.Tomaras S, Goetzke CC, Kallinich T, Feist E. Adult-Onset Still's Disease: Clinical Aspects and Therapeutic Approach. J Clin Med 2021;10:733. doi: 10.3390/jcm10040733
• 6.Franchini S, Dagna L, Salvo F. Efficacy of traditional and biologic agents in different clinical phenotypes of adult-onset Still's disease. Arthritis Rheum 2010;62:2530-5. doi: 10.1002/art.27532
• 7.Mimura, T, Kondo Y, Ohta A, et al. Evidence-based clinical practice guideline for adult Still's disease. Mod Rheumatol 2018;28:736-757. doi:10.1080/14397595.2018.1465633
• 8.Colafrancesco S, Manara M, Bortoluzzi A, et al. Correction to: Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and consensus-based statements by apanel of Italian experts. Arthritis Res Ther 2020;22:6. doi: 10.1186/s13075-019-2094-5
• 9.Junge G, Mason J, Feist E. Adult onset Still's disease-The evidence that anti-interleukin-1 treatment is effective and well-tolerated (a comprehensive literature review). Semin Arthritis Rheum 2017;47:295-302. doi: 10.1016/j.semarthrit.2017.06.006
• 10.Santarlasci V, Cosmi L, Maggi L, Liotta F, Annunziato F. IL-1and T Helper Immune Responses. Front Immunol 2013;15:4:182. doi: 10.3389/fimmu.2013.00182
• 11.Fautrel B. Adult-onset Still disease. Best Pract Res Clin Rheumatol 2008;22:773-92. doi: 10.1016/j.berh.2008.08.006
• 12.Ruscitti P, Cipriani P, Ciccia F, et al. Prognostic factors ofmacrophage activation syndrome, at the time of diagnosis, in adult patients affected by autoimmune disease: Analysis of 41cases collected in 2 rheumatologic centers. Autoimmun Rev 2017;16:16-21. doi: 10.1016/j.autrev.2016.09.016
• 13.Yamaguchi M, Ohta A, Tsunematsu T. Preliminary criteria for classification of adult Still's disease. J Rheumatol1992;19:424-30.
• 14.Rau M, Schiller M, Krienke S, et al. Clinical manifestations but not cytokine profiles differentiate adult-onset Still's disease and sepsis. J Rheumatol 2010;37:2369-76. doi: 10.3899/jrheum.100247
• 15.A Dinarello C. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011;117:3720-32. doi: 10.1182/blood-2010-07-273417
• 16.Colafrancesco S, Priori R, Alessandri C, et al. IL-18 Serum Level in Adult Onset Still's Disease: A Marker of DiseaseActivity. Int J Inflam 2012;2012:156890. doi: 10.1155/2012/156890.
• 17.Priori R, Colafrancesco S, Alessandr C, et al. Interleukin 18: a biomarker for differential diagnosis between adult-onset Still's disease and sepsis. J Rheumatol 2014;41:1118-23. doi: 10.3899/jrheum.130575
• 18.Colafrancesco S, Priori R, Valesini G. Presentation and diagnosis of adult-onset Still's disease: the implications ofcurrent and emerging markers in overcoming the diagnostic challenge. Expert Rev Clin Immunol 2015;11:749-61. doi: 10.1586/1744666X.2015.1037287
• 19.Rudinskaya A, H Trock D. Successful treatment of a patient with refractory adult-onset still disease with anakinra. J Clin Rheumatol 2003;9:330-2. doi: 10.1097/01.rhu.0000089966.48691.7f
• 20.Lequerré T, Quartier P, Rosellini D, et al. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis 2008;67:302-8. doi: 10.1136/ard.2007.076034
• 21.Hong D, Yang Z, Han S, et al. Interleukin 1 inhibition withanakinra in adult-onset Still disease: a meta-analysis of its efficacy and safety. Drug Des Devel Ther 2014;25:8:2345-57. doi: 10.2147/DDDT.S73428
• 22.Vitale A, Insalaco A, Sfriso P, et al. A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study. Front Pharmacol 2016;24:7:380. doi: 10.3389/fphar.2016.00380.
• 23.Colafrancesco S, Priori R, Valesini G. Response to Interleukin-1 Inhibitors in 140 Italian Patients with Adult-Onset Still's Disease: A Multicentre Retrospective Observational Study.Front Pharmacol 2017;13:8:369. doi: 10.3389/fphar.2017.00369
• 24.Kontzias A, Efthimiou P. The use of Canakinumab, a novel IL-1β long-acting inhibitor, in refractory adult-onset Still's disease. Semin Arthritis Rheum 2012;42:201-5. doi: 10.1016/j.semarthrit.2012.03.004
• 25.Barsotti S, Neri R, Iacopetti V, et al. Successful treatment ofrefractory adult-onset still disease with canakinumab: a case report. J Clin Rheumatol 2014;20:121. doi: 10.1097/RHU.0000000000000082
• 26.Lo Gullo A, Caruso A, Pipitone N, et al. Canakinumab in a case of adult onset still's disease: efficacy only on systemicmanifestations. Joint Bone Spine 2014;81:376-7. doi: 10.1016/j.jbspin.2013.12.011
• 27.Cavalli G, Farina N, Campochiaro C, Baldissera E, Dagna L.Current treatment options and safety considerations whentreating adult-onset Still's disease. Expert Opin Drug Saf 2020;19:1549-1558. doi: 10.1080/14740338.2020.1839411
• 28.Ravelli A, Grom AA, Behrens EM, Cron RQ. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun 2012;13:289-98. doi: 10.1038/gene.2012.3
• 29.Sönmez HE, Demir S, Bilginer Y, Özen S. Anakinra treatment in macrophage activation syndrome: a single center experience and systemic review of literatüre. Clin Rheumatol 2018;37:3329-3335. doi: 10.1007/s10067-018-4095-1
• 30.J Vastert S, de Jager W, Jan Noordman B, et al. Effectivenessof first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemicjuvenile idiopathic arthritis: results of a prospective cohortstudy. Arthritis Rheumatol 2014;66:1034-43. doi: 10.1002/art.38296
• 31.Vlak MH, Rinkel GJ, Greebe P, et al. Lifetime risks foraneurysmal subarachnoid haemorrhage: multivariable risk stratification. J Neurol Neurosurg Psychiatry 2013; 84:619-23. doi: 10.1136/jnnp-2012-303783.
• 32.Maruyama A, Kokuzawa A, Yamauchi Y, et al. Clinical features of elderly-onset Adult-onset Still’s disease. Mod Rheumatol. 2021 Jul;31(4):862-868. doi: 10.1080/14397595.2020.1829340.