Romatoid artrit yönetiminde subkutan yüksek doz metotreksat tedavisinin etkisi

Year 2021, Volume: 46 Issue: 3, 1150 - 1159, 30.09.2021

Müge Aydın Tufan , Emine Ersözlü Bozkırlı , Hamide Kart Ahmet Yücel

https://doi.org/10.17826/cumj.914892

Abstract

Amaç: Metotreksat (MTX), romatoid artrit (RA) için hala ana tedavi seçeneğidir. Tek başına veya diğer ilaçlarla kombinasyon halinde uygulandığında ilaç uygulama yolları ve dozajı konusunda fikir birliği yoktur. Bu çalışma, RA yönetiminde erken dönemde yüksek doz subkutan (SC) MTX içeren bir kombinasyon tedavisinin etkinliğini belirlemeyi amaçlamaktadır.
Gereç ve Yöntem: Yeni tanı almış kırk beş RA’lı hasta rastgele iki gruba ayrıldı. İlk 4 haftada, haftada 12,5 mg SC MTX alan hastalar "düşük doz grubu" olarak tanımlandı. İlk 4 haftada, haftada 25 mg SC MTX alan hastalar "yüksek doz grubu" olarak tanımlandı. Daha sonra her iki gruptaki hastalar haftada 12.5 mg oral MTX ile devam etti. Hastalara ait başlangıç, 3. ay ve 6. ay klinik ve laboratuvar bulguları, hastalık aktivite skorları ve yanıt oranları kaydedildi.
Bulgular: İki grup arasında 3. ay bulguları açısından anlamlı bir fark yoktu. 6. Ay değerleri açısından istatistiksel olarak anlamlı değişiklikler saptandı. Değerler düşük ve yüksek doz gruplarında şu şekildeydi: ortalama DAS28-CRP (3.5'e karşı 2.7; p = 0.01), VAS ağrı skoru (3.3'e karşı 1.6; p = 0.02) ve TJC28 (3'e karşı 1.5; p = 0.04), sırasıyla.
Sonuç: Bu çalışma, erken dönemde yüksek doz SC MTX uygulamasının, hastalık aktivitesini etkili bir şekilde kontrol ettiğini ve RA hastalarında yaşam kalitesini arttırdığını göstermiştir.

Keywords

İlaç uygulama yolları,, metotreksat, romatoid artrit,

Supporting Institution

YOK

Project Number

KA04/102

Effect of subcutaneous high-dose methotrexate treatment on the management of rheumatoid arthritis

Abstract

Purpose: Methotrexate (MTX) is still the main treatment option for rheumatoid arthritis (RA). There is no consensus on drug administration routes and dosage when administered alone or in combination with other drugs. This study aims to identify the effects of early administration of a combination therapy containing high dose subcutaneous (SC) MTX on RA management.
Materials and Methods: Forty-five patients with RA who newly diagnosed were divided into two groups randomly. The patients who took 12.5 mg SC MTX per week in the first 4 weeks defined as a "low dose group". The patients who took 25 mg SC MTX per week in the first 4 weeks defined as a "high dose group". Then, patients of both groups continued with 12.5 mg oral MTX per week. Clinical and laboratory findings, disease activity scores and response rates of the patients were recorded at the beginning, 3rd months and 6th months.
Results: There was no significant difference between the two groups at 3rd month’s values. There were statistically significant improvements at 6th month’s values. Values were as follows in low and high dose groups: mean DAS28-CRP (3.5 vs 2.7), VAS pain score (3.3 vs 1.6), and TJC28 (3 vs 1.5), respectively.
Conclusion: Early administration of high-dose SC MTX effectively controls disease activity and increases the quality of life in RA patients.

Keywords

Drug administration routes, methotrexate, rheumatoid arthritis,

Project Number

KA04/102

References

• References 1.Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009;68:1100-4.
• 2.Bianchi G, Caporali R, Todoerti M, Mattana P. Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration. Adv Ther. 2016;33:369-78.
• 3.Hazlewood GS, Barnabe C, Tomlinson G, Marshall D, Devoe D, Bombardier C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ. 2016;353:i1777.
• 4.Malaviya AN. Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story. Int J Rheum Dis. 2016;19:844-51.
• 5.Smolen JS, van Vollenhoven RF, Florentinus S, Chen S, Suboticki JL, Kavanaugh A. Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate. Ann Rheum Dis. 2018;77:1566-72.
• 6.Wasserman AM. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2011;84:1245-52.
• 7.Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79:685-99.
• 8.Schiff MH, Sadowski P. Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid arthritis. Rheumatol Int. 2017;37:213-8.
• 9.Sharma P, Scott DG. Optimizing Methotrexate Treatment in Rheumatoid Arthritis: The Case for Subcutaneous Methotrexate Prior to Biologics. Drugs. 2015;75:1953-6.
• 10.Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-24.
• 11.Choi S, Lee KH. Clinical management of seronegative and seropositive rheumatoid arthritis: A comparative study. PLoS One. 2018;13:e0195550.
• 12.Bijlsma JW, Weinblatt ME. Optimal use of methotrexate: the advantages of tight control. Ann Rheum Dis. 2007;66:1409-10.
• 13.Aletaha D, Smolen JS. Does Triple Conventional Synthetic Disease-Modifying Antirheumatic Drug Therapy Improve upon Methotrexate as the Initial Treatment of Choice for a Rheumatoid Arthritis Patient? Rheum Dis Clin North Am. 2019;45:315-24.
• 14.Moreland LW, O'Dell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012;64:2824-35.
• 15.Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet. 1999; 353:1568-73.
• 16.Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015;74:27-34.
• 17.Braun J, Kastner P, Flaxenberg P, Wahrisch J, Hanke P, Demary W, et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum. 2008;58:73-81.
• 18.Hazlewood GS, Thorne JC, Pope JE, Lin D, Tin D, Boire G, et al. The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis. Ann Rheum Dis. 2016;75:1003-8.
• 19.Altawil R, Saevarsdottir S, Wedren S, Alfredsson L, Klareskog L, Lampa J. Remaining Pain in Early Rheumatoid Arthritis Patients Treated With Methotrexate. Arthritis Care Res (Hoboken). 2016;68:1061-8.
• 20.Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018;158:502-16.