Methotrexate Use for Patients with Psoriasis and Risk of Cutaneous Squamous Cell Carcinoma: A Nested Case-control Study
DOI:
https://doi.org/10.2340/00015555-3725Keywords:
adverse effects, epidemiology, methotrexate, pharmacology, psoriasis, squamous cell carcinomaAbstract
An association between methotrexate use and risk of cutaneous squamous cell carcinoma has been reported in patients with rheumatoid and psoriatic arthritis. A nested case-control study was performed to investigate if methotrexate use among patients with psoriasis was associated with increased risk of cutaneous squamous cell carcinoma. Data were obtained from Swedish registers and included 623 patients with psoriasis and a first cutaneous squamous cell carcinoma from 2010 to 2016. Ten randomly selected patients with psoriasis were matched on age and sex to each case. Among cases, 160 (26%) were ever-users of methotrexate. The corresponding number among the controls was 1,370 (22%), yielding an unadjusted odds ratio (OR) of 1.23 (95% confidence interval (95% CI) 1.02–1.49); p = 0.034. After adjusting for use of other immunosuppressive drugs the association was close to unity (OR 1.09; 95% CI 0.89–1.34); p = 0.39. The slightly increased risk of cutaneous squamous cell carcinoma associated with methotrexate-exposure in patients with psoriasis does not seem to be associated with methotrexate, but rather with disease severity, other anti-psoriatic treatments, and ultraviolet exposure.
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Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F, Bouvard V, et al. A review of human carcinogens - Part A: pharmaceuticals. Lancet Oncol 2009; 10: 13-14.
DOI: https://doi.org/10.1016/S1470-2045(08)70286-9
Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2009; 60: 824-837.
DOI: https://doi.org/10.1016/j.jaad.2008.11.906
Lange E, Blizzard L, Venn A, Francis H, Jones G. Disease-modifying anti-rheumatic drugs and non-melanoma skin cancer in inflammatory arthritis patients: a retrospective cohort study. Rheumatology (Oxford) 2016; 55: 1594-1600.
DOI: https://doi.org/10.1093/rheumatology/kew214
Scott FI, Mamtani R, Brensinger CM, Haynes K, Chiesa-Fuxench ZC, Zhang J, et al. Risk of nonmelanoma skin cancer associated with the use of immunosuppressant and biologic agents in patients with a history of autoimmune disease and nonmelanoma skin cancer. JAMA Dermatol 2016; 152: 164-172.
DOI: https://doi.org/10.1001/jamadermatol.2015.3029
deShazo R, Soltani-Arabshahi R, Krishnasamy S, Langley RG, Kalia S, Stahle M, et al. Non-melanoma skin cancer risk among patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol 2019; 18: 1059-1060.
Boffetta P, Gridley G, Lindelof B. Cancer risk in a population-based cohort of patients hospitalized for psoriasis in Sweden. J Invest Dermatol 2001; 117: 1531-1537.
DOI: https://doi.org/10.1046/j.0022-202x.2001.01520.x
Ji J, Shu X, Sundquist K, Sundquist J, Hemminki K. Cancer risk in hospitalised psoriasis patients: a follow-up study in Sweden. Br J Cancer 2009; 100: 1499-1502.
DOI: https://doi.org/10.1038/sj.bjc.6605027
Trafford AM, Parisi R, Kontopantelis E, Griffiths CEM, Ashcroft DM. Association of psoriasis with the risk of developing or dying of cancer: a systematic review and meta-analysis. JAMA Dermatol 2019; 155: 1390-1403.
DOI: https://doi.org/10.1001/jamadermatol.2019.3056
Vaengebjerg S, Skov L, Egeberg A, Loft ND. Prevalence, incidence, and risk of cancer in patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis. JAMA Dermatol 2020; 156: 421-429.
DOI: https://doi.org/10.1001/jamadermatol.2020.0024
Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, et al. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med 2019; 380: 752-762.
DOI: https://doi.org/10.1056/NEJMoa1809798
Solomon DH, Glynn RJ, Karlson EW, Lu F, Corrigan C, Colls J, et al. Adverse effects of low-dose methotrexate: a randomized trial. Ann Intern Med 2020; 172: 369-380.
DOI: https://doi.org/10.7326/M19-3369
Polesie S, Gillstedt M, Paoli J, Osmancevic A. Methotrexate treatment for patients with psoriasis and risk of cutaneous melanoma: a nested case-control study. Br J Dermatol 2020; 183: 684-691.
DOI: https://doi.org/10.1111/bjd.18887
Rothman KJ, Greenland S, Lash TL. Modern epidemiology. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, PA, US, 2008.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-383.
DOI: https://doi.org/10.1016/0021-9681(87)90171-8
Bykerk VP. A Call to Systematically monitor for adverse events in users of low-dose methotrexate therapy. Ann Intern Med 2020; 172: 425-426.
DOI: https://doi.org/10.7326/M20-0435
Raaschou P, Simard JF, Asker Hagelberg C, Askling J. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. BMJ 2016; 352: i262.
DOI: https://doi.org/10.1136/bmj.i262
Archier E, Devaux S, Castela E, Gallini A, Aubin F, Le Maitre M, et al. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol 2012; 26: 22-31.
DOI: https://doi.org/10.1111/j.1468-3083.2012.04520.x
Lim JL, Stern RS. High levels of ultraviolet B exposure increase the risk of non-melanoma skin cancer in psoralen and ultraviolet A-treated patients. J Invest Dermatol 2005; 124: 505-513.
DOI: https://doi.org/10.1111/j.0022-202X.2005.23618.x
Lindelof B, Sigurgeirsson B, Tegner E, Larko O, Johannesson A, Berne B, et al. PUVA and cancer risk: the Swedish follow-up study. Br J Dermatol 1999; 141: 108-112.
DOI: https://doi.org/10.1046/j.1365-2133.1999.02928.x
Stern RS. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Dermatol 2012; 66: 553-562.
DOI: https://doi.org/10.1016/j.jaad.2011.04.004
Osmancevic A, Gillstedt M, Wennberg AM, Larkö O. The risk of skin cancer in psoriasis patients treated with UVB therapy. Acta Derm Venereol 2014; 94: 425-430.
DOI: https://doi.org/10.2340/00015555-1753
Black RJ, Gavin AT. Photocarcinogenic risk of narrowband ultraviolet B (TL-01) phototherapy: early follow-up data. Br J Dermatol 2006; 154: 566-567.
DOI: https://doi.org/10.1111/j.1365-2133.2005.07085.x
Hearn RM, Kerr AC, Rahim KF, Ferguson J, Dawe RS. Incidence of skin cancers in 3867 patients treated with narrow-band ultraviolet B phototherapy. Br J Dermatol 2008; 159: 931-935.
DOI: https://doi.org/10.1111/j.1365-2133.2008.08776.x
Man I, Crombie IK, Dawe RS, Ibbotson SH, Ferguson J. The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data. Br J Dermatol 2005; 152: 755-757.
DOI: https://doi.org/10.1111/j.1365-2133.2005.06537.x
Weischer M, Blum A, Eberhard F, Rocken M, Berneburg M. No evidence for increased skin cancer risk in psoriasis patients treated with broadband or narrowband UVB phototherapy: a first retrospective study. Acta Derm Venereol 2004; 84: 370-374.
DOI: https://doi.org/10.1080/00015550410026948
Guorgis G, Anderson CD, Lyth J, Falk M. Actinic keratosis diagnosis and increased risk of developing skin cancer: a 10-year cohort study of 17,651 patients in Sweden. Acta Derm Venereol 2020; 100: adv00128.
DOI: https://doi.org/10.2340/00015555-3486
George R, Weightman W, Russ GR, Bannister KM, Mathew TH. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol 2002; 43: 269-273.
DOI: https://doi.org/10.1046/j.1440-0960.2002.00613.x
Harwood CA, Leedham-Green M, Leigh IM, Proby CM. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol 2005; 141: 456-464.
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