Effectiveness of Methotrexate Versus Cyclosporine in the Management of Moderate to Severe Atopic Dermatitis- Meta-Analysis of Randomised Controlled Trials

Authors

  • Sakina Sadiq Malik Department of Dermatology, Pak Emirates Military Hospital/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan
  • Ayesha Anwar Department of Dermatology, Pak Emirates Military Hospital/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan
  • Aisha Akhtar Department of Dermatology, Pak Emirates Military Hospital/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan
  • Farrah Yousaf Department of Dermatology, Pak Emirates Military Hospital/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan
  • Uzma Bashir Department of Dermatology, Pak Emirates Military Hospital/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan
  • Saadia Malik Department of Dermatology, Pak Emirates Military Hospital/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan

DOI:

https://doi.org/10.51253/pafmj.v74i2.12080

Keywords:

Atopic dermatitis, Ciclosporin, Cyclosporine, Meta-analysis, Methotrexate

Abstract

Objective: To compare the effectiveness of Methotrexate (MTX) versus Cyclosporine (CyA) in the patients of moderate to severe atopic dermatitis (AD)

Study Design: Systematic review and Meta-analysis.

Methodology: After formulating our research team and PICO question rationally, a search strategy and literature search were carried out as per Cochrane guidelines. Full-text articles were retrieved after title and abstract screening per our inclusion criteria. The whole search process was documented in the form of a PRISMA flow chart. Team members made and filed data extraction sheets, and qualitative data synthesis was performed. Afterwards, a meta-analysis was carried out, involving a total of 03 randomized controlled trials. Revman was used to process the continuous and dichotomous data collected for our outcomes. RoB 2 was used to assess the risk of bias in the included studies. Grade pro-GDT was used to summarize the findings in the table.

Results: Pooled results from 3 RCTs showed that CyA in a 2.5mg/kg dose is better than MTX @0.4 mg/kg/week at 12 weeks in AD. At follow-up, MTX maintains better disease control, i.e., until 24 weeks post-treatment. MTX has a better safety profile than CyA.

Conclusion: MTX and CyA are both effective drugs for moderate to severe AD, but they have their pros and cons.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Akhavan A, Rudikoff D. The treatment of atopic dermatitis with systemic immunosuppressive agents. Clin Dermatol 2003; 21(3): 225–40. https://doi.org/10.1016/S0738-081X(02)00362-0

Man SLP, Bouzillé G, Beneton N, Safa G, Dupuy A, Droitcourt C, et al. Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis: comparison between methotrexate and cyclosporine. J Eur Acad Dermatol Venereol 2018; 32(8): 1327-1335. https://doi.org/10.1111/jdv.14880

Celakovská J, Bukač J. The severity of atopic dermatitis evaluated with the SCORAD index and the occurrence of bronchial asthma and rhinitis, and the duration of atopic dermatitis. Allergy Rhinol 2016; 7(1): 8-13. https://doi.org/10.2500/ar.2016.7.0144

Vakharia PP, Chopra R, Silverberg JI. Systematic Review of Diagnostic Criteria Used in Atopic Dermatitis Randomized Controlled Trials. Am J Clin Dermatol 2018; 19(1): 15-22. https://doi.org/10.1007/s40257-017-0299-4

Akan A, Dibek-Mısırlıoğlu E, Civelek E, Vezir E, Kocabaş CN. Diagnosis of atopic dermatitis in children: comparison of the Hanifin-Rajka and the United Kingdom Working Party criteria. Allergol Immunopathol 2020;48(2): 175–181. https://doi.org/10.1016/j.aller.2019.07.008

Chopra R, Silverberg JI. Assessing the severity of atopic dermatitis in clinical trials and practice. Clin Dermatol 2018; 36(5): 606-615. https://doi.org/10.1016/j.clindermatol.2018.05.012

Fishbein AB, Silverberg JI, Wilson EJ, Ong PY. Update on Atopic Dermatitis: Diagnosis, Severity Assessment, and Treatment Selection. J Allergy Clin Immunol Pract 2020; 8(1): 91-101. https://doi.org/10.1016/j.jaip.2019.06.044

Chu AWL, Wong MM, Rayner DG, Guyatt GH, Díaz Martinez JP, Ceccacci R, et al. Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials. J Allergy Clin Immunol 2023; 152(6): 1470-1492. https://doi.org/10.1016/j.jaci.2023.08.029

Chu DK, Schneider L, Asiniwasis RN, Boguniewicz M, De Benedetto A, Ellison K, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations. Ann Allergy Asthma Immunol 2024; 132(3): 274-312. https://doi.org/10.1016/j.anai.2023.11.009

Eckert L, Amand C, Gadkari A, Rout R, Hudson R, Ardern-Jones M, et al. Treatment patterns in UK adult patients with atopic dermatitis treated with systemic immunosuppressants: data from The Health Improvement Network (THIN). J Dermatolog Treat 2020; 31(8): 815-820. https://doi.org/10.1080/09546634.2019.1639604

Drucker AM, Morra DE, Prieto-Merino D, Ellis AG, Yiu ZZN, Rochwerg B, et al. Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis. JAMA Dermatol 2022; 158(5): 523-532. https://doi.org/10.1001/jamadermatol.2022.0455

Drucker AM, Ellis AG, Bohdanowicz M, Mashayekhi S, Yiu ZZN, Rochwerg B, et al. Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis. JAMA Dermatol 2020; 156(6): 659-667. https://doi.org/10.1001/jamadermatol.2020.0796

El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. Eur J Pediatr 2013; 172(3): 351-356. https://doi.org/ 10.1007/s00431-012-1893-3

Goujon C, Viguier M, Staumont-Sallé D, Bernier C, Guillet G, Lahfa M, et al. Methotrexate Versus Cyclosporine in Adults with Moderate-to-Severe Atopic Dermatitis: A Phase III Randomized Noninferiority Trial. J Allergy Clin Immunol Pract 2018; 6(2): 562-569.e3. https://doi.org/10.1016/j.jaip.2017.07.007

Irvine AD, Jones AP, Beattie P, Baron S, Browne F, Ashoor F; et al. TREAT Trial Investigators. A randomized controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT). Br J Dermatol 2018; 179(6): 1297-1306. https://doi.org/10.1111/bjd.16717

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372:n71. https://doi.org/10.1136/bmj.n71

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. Cochrane Handbook for Systematic Reviews of Interventions; 2019.

Liu J, Liu C, Hua C. Risk bias assessment tool RoB2 (revised version 2019) for randomized controlled trial: An interpretation. Chin J Evid Base Med 2021; 21(6). https://doi.org/10.7507/1672-2531.202011144

Lee JH, Yun SJ, Lee JB, Lee SC. Therapeutic Efficacy and Safety of Methotrexate in Moderate-to-Severe Atopic Dermatitis: A Retrospective Study of Korean Patients at Tertiary Referral Hospital. Ann Dermatol 2020; 32(5): 402-408. https://doi.org/10.5021/ad.2020.32.5.402

Védie AL, Ezzedine K, Amazan E, Boralevi F, Milpied B, Taïeb A, et al. Long-term use of systemic treatments for moderate-to-severe atopic dermatitis in adults: A monocentric retrospective study. Acta Derm Venereol 2016; 96(6): 802–806. https://doi.org/10.2340/00015555-2389

Flohr C, Rosala-Hallas A, Jones AP, Beattie P, Baron S, Browne F, et al. TREAT Trial Investigators. Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial. Br J Dermatol 2023; 189(6): 674-684. https://doi.org/10.1093/bjd/ljad281

Busger Op Vollenbroek FTM, Doggen CJM, Janssens RWA, Bernelot Moens HJ. Dermatological guidelines for monitoring methotrexate treatment reduce drug-survival compared to rheumatological guidelines. PLoS One 2018; 13(3): e0194401. https://doi.org/10.1371/journal.pone.0194401

Warren RB, Weatherhead SC, Smith CH, Exton LS, Mohd Mustapa MF, Kirby B, et al. British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016. Br J Dermatol 2016; 175(1): 23-44. https://doi.org/10.1111/bjd.14816

Griffiths CEM, Katsambas A, Dijkmans BAC, Finlay AY, Ho VC, Johnston A, et al. Update on the use of ciclosporin in immune-mediated dermatoses. Br J Dermatol 2006:155. https://doi.org/10.1111/j.1365-2133.2006.07343.x

Muka T, Glisic M, Milic J, Verhoog S, Bohlius J, Bramer W, et al. A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research. Eur J Epidemiol 2020; 35(1): 49-60. https://doi.org/10.1007/s10654-019-00576-5

Downloads

Published

29-04-2024

How to Cite

1.
Sadiq Malik S, Anwar A, Akhtar A, Yousaf F, Bashir U, Malik S. Effectiveness of Methotrexate Versus Cyclosporine in the Management of Moderate to Severe Atopic Dermatitis- Meta-Analysis of Randomised Controlled Trials. Pak Armed Forces Med J [Internet]. 2024 Apr. 29 [cited 2024 May 21];74(2):574-82. Available from: https://www.pafmj.org/PAFMJ/article/view/12080

Issue

Section

Review Articles

Most read articles by the same author(s)

1 2 > >>