Sistemik olmayan juvenil idiyopatik artrit tedavisinde biyolojik monoterapi ile biyolojik ve hastalık modifiye edici anti-romatizmal ilaç kombinasyonunun karşılaştırılması

Öz

Amaç Jüvenil idiyopatik artrit (JİA) tedavisinde konvansiyonel hastalık modifiye edici anti-romatizmal ilaçlar (cDMARD'lar) ile mono veya kombinasyon tedavisi olarak biyolojiklerin etkinliğini karşılaştırmak. Gereç ve Yöntem Ocak 2020- 2023 arasında kadar izlenen monoterapi olarak biyolojik ilaçlarla veya cDMARD kombinasyonuyla tedavi edilen hastaların tıbbi kayıtları retrospektif olarak incelendi. Demografik özellikler, klinik skorlar ve tedavi verileri değerlendirildi. Sonuçlar Tek başına veya JIA için bir cDMARD ile kombinasyon halinde etanersept, adalimumab veya tosilizumab alan 205 vaka dahil edildi. Grubun kadın erkek oranı hemen hemen eşitti. Oligoartiküler JİA'nın en yaygın alt tipiydi. Grubun büyük çoğunluğu (n=128, %62,4) biyolojik ilaçları monoterapi olarak alırken, geri kalan üçte birlik kısım (n=77, %37,6) biyolojik ve bir cDMARD kombinasyonu kullanmıştı. Grubun yaklaşık yarısı (%57,1) etanersept ile tedavi edilmişti ve jüvenil psoriatik artrit dışında tüm JİA alt tipleri arasında en sık kullanılan etanersept monoterapisiydi. Jüvenil psoriatik artritli çocukların çoğuna adalimumab kombinasyon tedavisi verildi. Hastalığın başlangıcında üveitli 8 hastanın hepsinde tek başına veya metotreksat ile kombinasyon halinde adalimumab tercih edildi. Takip sırasında üveit gelişenlerde adalimumab kombine (n=9) ve tosilizumab monoterapisi (n=4) en yaygın biyolojik ilaçlardı. Tartışma Etanersept, adalimumab ve tosilizumab JİA tedavisinde etkili ve güvenli biyolojik ilaçlardır. Maliyet etkin özellikleri göz önüne alındığında, biyolojik ilaçların zamanında kombine veya monoterapi olarak seçilmesi, JİA'nın erken ve geç sekellerini önlemede etkilidir.

Anahtar Kelimeler

• Juvenil idiyopatik artrit
• biyolojik ilaç
• hastalık modifiye edici anti-romatizmal ilaçlar

Comparison of biologic monotherapy versus biologic and disease-modifying anti-rheumatic drug combination in the treatment of non-systemic juvenile idiopathic arthritis

Öz

Purpose To explore the efficacy of biologics as mono- or combination therapy with conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of juvenile idiopathic arthritis (JIA). Material and Methods Medical records of patients with JIA followed-up from January 2020 to 2023 who were treated either with biologic drugs as monotherapy or with combination of cDMARD were reviewed retrospectively. Data of demographic features, clinical scores and treatments were assessed. Results Two hundred five cases received etanercept, adalimumab, or tocilizumab alone or in combination with a cDMARD for JIA were included. The male to female ratio of the cohort was almost equal. Oligoarticular was the most common subtype of JIA. Majority (n=128, 62.4%) of the group received biologic drugs as monotherapy, while the remaining third (n=77, 37.6%) used a combination of biologic and a cDMARD. Nearly half of the group (57.1%) were treated with etanercept and etanercept monotherapy was the most commonly used one among all JIA subtypes except juvenile psoriatic arthritis. Adalimumab combination therapy was prescribed in most of the children with juvenile psoriatic arthritis. Adalimumab, alone or in combination with methotrexate, was preferred for all 8 patients with uveitis at the onset of the disease. Adalimumab combined (n=9) and tocilizumab monotherapy (n=4) were the most common biologics in those who developed uveitis during follow-up. Conclusion Etanercept, adalimumab, or tocilizumab are effective and safe biologics in treatment of JIA. Considering their cost-effective properties, choosing biologic drugs timely as combined or monotherapy is effective in preventing early and late sequelae of JIA.

Anahtar Kelimeler

• Juvenile idiopathic arthritis
• biologic medications
• disease-modifying anti-rheumatic drugs

Kaynakça

1. Petty RE, Southwood TR, Manners P,Baum J, Glass DN, Goldenburg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390-2.
2. Danner S, Sordet C, Terzic J, Donato L, Velten M, Fischbach M, et al. Epidemiology of juvenile idiopathic arthritis in Alsace, France. J Rheumatol 2006;33:1377-81.
3. Horneff G, De Bock F, Foeldvari I, Girschick H J, Michels H, Moebius D, et al. Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis 2009;68:519-25.
4. Zhang T, Huang S, Guo Y, Jin J, Yan W, Wang P, et al. Effectiveness of tumor necrosis factor inhibitors in children with enthesitis-related arthritis: a single-center retrospective analysis. Front Pediatr 2023;11:1122233.
5. Krüger K. Combination therapy using methotrexate with DMARDs or biologics--current status. Z Rheumatol 2011;70:114-22.
6. Klein A. Biologics in the treatment of juvenile idiopathic arthritis : A comparison of mono- and combination therapy with synthetic DMARDs. Z Rheumatol 2019;78:599-609.
7. Alexeeva E, Dvoryakovskaya T, Denisova R, Sleptsova T, Isaeva K, Chomahhidze A, et al. Dynamics of concomitant therapy in children with juvenile idiopathic arthritis treated with etanercept and methotrexate. Pediatr Neonatol 2019;60:549-55.
8. Alexeeva E, Horneff G, Dvoryakovskaya T, Denisova R, Nikishina I, Zholobova E, et al. Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial. Pediatr Rheumatol Online J 2021;19:5.

9. Bulatović Ćalasan M, de Vries LD, Vastert SJ, Heijstek MW, Wulffraat NM. Interpretation of the Juvenile Arthritis Disease Activity Score: responsiveness, clinically important differences and levels of disease activity in prospective cohorts of patients with juvenile idiopathic arthritis. Rheumatology 2013;53:307-12.
10. Wallace CA, Ruperto N, Giannini E. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004;31:2290-4.
11. Levälampi T, Kärki J, Rebane K, Vahasalo P, Malin M, Kroger L, et al. Etanercept for patients with juvenile idiopathic arthritis: drug levels and influence of concomitant methotrexate: observational study. Pediatr Rheumatol Online J 2023;21:27.
12. Verstegen RHJ, Shrader P, Balevic SJ, Beukelman T, Correll C, Dennos A, et al. Dosing Variation at Initiation of Adalimumab and Etanercept and Clinical Outcomes in Juvenile Idiopathic Arthritis: A Childhood Arthritis and Rheumatology Research Alliance Registry Study. Arthritis Care Res (Hoboken) 2023;75:410-22.
13. Horneff G, Schmeling H, Biedermann T, Foeldvari I, Ganser G, Girschinck HJ, et al. The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 2004;63:1638-44.
14. Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, et al. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum 2009;60:2794-804.
15. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med 2000;342:763-9.
16. Klein A, Becker I, Minden K, Foeldvari I, Haas JP, Horneff G. Adalimumab versus adalimumab and methotrexate for the treatment of juvenile idiopathic arthritis: long-term data from the German BIKER registry. Scand J Rheumatol 2019;48:95-104.
17. Ramanan AV, Dick AD, Jones AP, Hughes D, Mckay A, Hallas AR, et al. Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT. Health Technol Assess 2019;23:1-140.
18. Nassar-Sheikh Rashid A, Schonenberg-Meinema D, Bergkamp SC, Bakhlakh S, Vries A, Rispens T, et al. Therapeutic drug monitoring of anti-TNF drugs: an overview of applicability in daily clinical practice in the era of treatment with biologics in juvenile idiopathic arthritis (JIA). Pediatr Rheumatol Online J 2021;19:59.
19. Atiqi S, Hooijberg F, Loeff FC, Rispens T, Wolbink GJ. Immunogenicity of TNF-Inhibitors. Front Immunol 2020;11:312.
20. Machado SH, Xavier RM. Safety of tocilizumab in the treatment of juvenile idiopathic arthritis. Expert Opin Drug Saf 2017;16:493-500.
21. Iannone C, Marelli L, Costi S, Pellico MR, La Franca L, Caporali R, et al. Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis, a Narrative Review. Children (Basel) 2023;10: 434.
22. Frampton JE. Tocilizumab: A Review of Its Use in the Treatment of Juvenile Idiopathic Arthritis. Pediatric Drugs 2013;15:515-31.
23. Thiele F, Klein A, Klotsche J, Windschall D, Dressler F, Kuemmerle Deschner J, et al. Biologics with or without methotrexate in treatment of polyarticular juvenile idiopathic arthritis: effectiveness, safety and drug survival. Rheumatology (Oxford) 2023;62:2230-8.