Jüvenil İdiopatik Artritli Hastalarda Leflunomid Tedavisinin Değerlendirilmesi: Tek Merkez Deneyimi

Year 2023, Volume: 17 Issue: 3, 214 - 218, 29.05.2023

Elif Arslanoğlu Aydın , Semanur Özdel , Ilknur Bagrul , Nesibe Gokce Kocamaz , Esra Bağlan , Serife Tuncez , Mehmet Bulbul

https://doi.org/10.12956/tchd.1212198

Abstract

Amaç: Juvenil idiyopatik artrit (JİA), çocukluk çağının en sık görülen kronik romatizmal hastalığıdır. Metotreksat (MTX), leflunomid (LFN) gibi hastalık modifiye edici antiromatizmal ilaçlar (DMARD) JİA'da birinci basamak tedavilerdir. MTX en sık reçete edilen ilaçtır ve çalışmalar ağırlıklı olarak MTX etkinliğini ve güvenliğini ele almaktadır. Ancak LFN ile ilgili veriler sınırlıdır. Bu çalışmada, JİA hastalarında LFN tedavisi ile ilgili kliniğimizin deneyimlerini sunmayı amaçladık.
Gereç ve Yöntem: Bu retrospektif çalışmaya hastanemiz çocuk romatoloji polikliniğinde düzenli olarak takip edilen ve LFN tedavisi verilmiş JİA hastaları dahil edildi. Hasta demografik bilgileri, klinik ve laboratuvar özellikleri ile ilgili veriler tıbbi dosyalardan elde edildi.
Bulgular: Çalışmaya ortanca (çeyrekler arası aralık) hastalık başlangıç yaşı 7,3 (3,1-12,0) yıl olan 18 hasta (15 kadın ve 3 erkek) dahil edildi. 8 hastada oligoartiküler JİA, 7 hastada poliartiküler JİA, 2 hastada sistemik JİA ve 1 hastada entezitle ilişkili artrit (ERA) vardı. Tüm hastalara başlangıç tedavisi olarak MTX verildi (ERA tanısı konan bir hasta sulfasalazin ile tedavi edildi hariç). Gastrointestinal sistem (GİS) intoleransı nedeniyle başlangıçta MTX alan tüm hastalarda MTX kesildi ve LFN tedavisi başlandı. Daha önce MTX alırken GİS intoleransı gelişen hastalık aktivitesi düşük olan yedi hastadan altısına LFN tedavisi verildi. Bu hastalarda LFN ile tam remisyon sağlandı. MTX ile remisyonda izlenen dört hastada hastalık aktivasyonu görüldü. Daha önce MTX intoleransı olan bu hastalara LFN tedavisi verildi. Dört hastanın üçünde LFN ile remisyon sağlandı. MTX ile remisyon sağlanamayan orta ve yüksek hastalık aktivitesine sahip altı hastaya biyolojik tedavi başlandı. Yeterli yanıt alınamayan bu hastalarda MTX kesilerek LFN tedavisi başlandı. LFN ve biyolojik ajan kombinasyonu ile sadece bir hastada inaktif hastalık elde edildi. ERA tanılı bir hastada sulfasalazin tedavisine yetersiz yanıt alması üzerine LFN tedavisine geçildi ve LFN ile tam remisyon elde edildi.
Sonuçlar: LFN tedavisi, diğer DMARD'larla düşük hastalık aktivitesi ve/veya remisyonu olan ve ilaç kesildikten sonra nüks olan hastalarda faydalı olabilir.

Keywords

Hastalık modifiye edici antiromatizmal ilaç, jüvenil idiyopatik artrit, Leflunomid

Evaluation Of Leflunomide Treatment In Patients With Juvenile Idiopathic Arthritis: A Single Center Experience

Abstract

Aim: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. Disease-modifying antirheumatic drugs (DMARD) such as methotrexate (MTX), leflunomide (LFN) are first-line treatment in JIA. MTX is the most commonly prescribed drug. Studies predominantly demonstrate the efficacy and safety of it, but the data on LFN are limited. This study aimed to present our experience with LFN treatment in JIA patients.
Materials and Methods: This retrospective study included JIA patients who were followed-up regularly and had received LFN. Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts.
Results: The study included 18 patients (15 female and 3 male) with a median (interquartile range) age at onset of disease 7.3 (3.1-12.0) years. Among them, 8 had oligoarticular JIA, seven had polyarticular JIA, two had systemic JIA and one had enthesitis-related arthritis (ERA). All patients received MTX as initial therapy (except one patient diagnosed with ERA was treated with sulfasalazine). MTX was discontinued and LFN treatment was started in all patients who initially received MTX due to gastrointestinal system (GIS) intolerance. Six of 7 patients with low disease activity, who had GIS intolerance while taking MTX before, were given LFN treatment because the disease activity was low. These patients achieved a complete remission with LFN. Four patients followed in remission with MTX had disease activation. These patients, who had previously experienced MTX intolerance, were given LFN treatment. Remission was achieved with LFN in 3 of 4 patients. Biological therapy was started in 6 patients with moderate or high disease activity who could not achieve remission with only MTX. These patients who did not have an adequate response were swicthed to LFN. Inactive disease was obtained in only 1 patient with the combination of LFN and biological agent. The patient with ERA was switched to LFN treatment due to inadequate response to sulfasalazine treatment. This patient achieved a complete remission with LFN.
Conclusions: LFN therapy may be beneficial in patients with low disease activity and/ or remission with other DMARDs and relapse after drug discontinuation.

Keywords

Disease-modifying antirheumatic drug, Juvenile idiopathic arthritis, Leflunomide

References

• Zaripova LN, Midgley A, Christmas SE, Beresford MW, Baildam EM, Oldershaw RA. Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol Online J 2021;19:135.
• Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390-2.
• Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken) 2019;71:717-34.
• Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, et al. Leflunomide for the treatment of rheumatoid arthritis: A systematic review and metaanalysis. J Rheumatol 2003;30:1182-90.
• McErlane F, Beresford MW, Baildam EM, Chieng SE, Davidson JE, Foster HE, et al. Validity of a three-variable juvenile arthritis disease activity score in children with new-onset juvenile idiopathic arthritis. Ann Rheum Dis 2013;72:1983-8.
• Akkoc Y, Karatepe AG, Akar S, Kirazli Y, Akkoc N. A Turkish version of the bath ankylosing spondylitis disease activity index: reliability and validity. Rheumatol Int 2005;25:280-4.
• Chickermane PR, Khubchandani RP. Evaluation of the benefits of sequential addition of leflunomide in patients with polyarticular course juvenile idiopathic arthritis failing standard dose methotrexate. Clin Exp Rheumatol 2015;33:287-92. 
• Silverman E, Mouy R, Spiegel L, Jung LK, Saurenmann RK, Lahdenne P, et al. Leflunomide in Juvenile Rheumatoid Arthritis (JRA) Investigator Group. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med 2005;352:1655-66.
• Foeldvari I, Wierk A. Effectiveness of leflunomide in patients with juvenile idiopathic arthritis in clinical practice. J Rheumatol 2010;37:1763-7.
• Alcântara AC, Leite CA, Leite AC, Sidrim JJ, Silva FS Jr, Rocha FA. A longterm prospective real-life experience with leflunomide in juvenile idiopathic arthritis. J Rheumatol 2014;41:338-44.
• Aktay Ayaz N, Karadağ ŞG, Çakmak F, Çakan M, Tanatar A, Sönmez HE. Leflunomide treatment in juvenile idiopathic arthritis. Rheumatol Int 2019;39:1615-9.
• Rozman B. Clinical experience with leflunomide in rheumatoid arthritis. Leflunomide Investigators’ Group. J Rheumatol Suppl 1998;53:27-32.