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Cancer Cell International
Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | Melanoma | Review

Risk of non-melanoma skin cancer with biological therapy in common inflammatory diseases: a systemic review and meta-analysis

Authors: Ruolin Liu, Qianyi Wan, Rui Zhao, Haitao Xiao, Ying Cen, Xuewen Xu

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown.

Methods

We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model.

Results

The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years.

Conclusions

Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.
Appendix
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Literature
1.
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–38.PubMed
2.
Kamm MA. Rapid changes in epidemiology of inflammatory bowel disease. Lancet. 2017;390(10114):2741–2.PubMed
3.
Parisi R, Iskandar IYK, Kontopantelis E, Augustin M, Griffiths CEM, Ashcroft DM. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study. Bmj. 2020;369:m1590.PubMedPubMedCentral
4.
5.
Singh S, Nagpal SJ, Murad MH, Yadav S, Kane SV, Pardi DS, Talwalkar JA, Loftus EV Jr. Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12(2):210–8.PubMed
6.
Ishiyama K, Suwa A, Goto M, Hirakata M, Inoue K, Hara M, Inada S. Malignant melanoma in a patient with rheumatoid arthritis. Clin Exp Rheumatol. 1998;16(4):507.PubMed
7.
8.
Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390-399.e391.PubMed
9.
Amari W, Zeringue AL, McDonald JR, Caplan L, Eisen SA, Ranganathan P. Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis. Rheumatology. 2011;50(8):1431–9.PubMed
10.
Wang X, Liu Q, Wu L, Nie Z, Mei Z. Risk of non-melanoma skin cancer in patients with psoriasis: an updated evidence from systematic review with meta-analysis. J Cancer. 2020;11(5):1047–55.PubMedPubMedCentral
11.
Chatzikyriakidou A, Georgiou I, Voulgari PV, Drosos AA. The role of tumor necrosis factor (TNF)-alpha and TNF receptor polymorphisms in susceptibility to ankylosing spondylitis. Clin Exp Rheumatol. 2009;27(4):645–8.PubMed
12.
Narazaki M, Tanaka T, Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol. 2017;13(6):535–51.PubMed
13.
14.
Ruiz de Morales JMG, Puig L, Daudén E, Cañete JD, Pablos JL, Martín AO, Juanatey CG, Adán A, Montalbán X, Borruel N, et al. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: an updated review of the evidence focusing in controversies. Autoimmun Rev. 2020;19(1):102429.PubMed
15.
Naldi L. Biologic treatment for psoriasis and cancer: an increased risk for most cancers could not be ruled out. Br J Dermatol. 2018;178(1):19.PubMed
16.
Esse S, Mason KJ, Green AC, Warren RB. Melanoma risk in patients treated with biologic therapy for common inflammatory diseases: a systematic review and meta-analysis. JAMA Dermatol. 2020;156(7):787–94.PubMed
17.
van Lumig PP, Menting SP, van den Reek JM, Spuls PI, van Riel PL, van de Kerkhof PC, Fransen J, Kievit W, de Jong EM. An increased risk of non-melanoma skin cancer during TNF-inhibitor treatment in psoriasis patients compared to rheumatoid arthritis patients probably relates to disease-related factors. J Eur Acad Dermatol Venereol. 2015;29(4):752–60.PubMed
18.
Peleva E, Exton LS, Kelley K, Kleyn CE, Mason KJ, Smith CH. Risk of cancer in patients with psoriasis on biological therapies: a systematic review. Br J Dermatol. 2018;178(1):103–13.PubMed
19.
Muller M, D’Amico F, Bonovas S, Danese S, Peyrin-Biroulet L. TNF inhibitors and risk of malignancy in patients with inflammatory bowel diseases: a systematic review. J Crohns Colitis. 2021;15(5):840–59.PubMed
20.
Singh A, Fatima K, Srivastava A, Khwaja S, Priya D, Singh A, Mahajan G, Alam S, Saxena AK, Mondhe DM, et al. Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer. Chem Biol Drug Des. 2016;88(5):625–34.PubMed
21.
Xie W, Yang X, Huang H, Gao D, Ji L, Zhang Z. Risk of malignancy with non-TNFi biologic or tofacitinib therapy in rheumatoid arthritis: a meta-analysis of observational studies. Semin Arthr Rheum. 2020;50(5):930–7.
22.
Wang JL, Yin WJ, Zhou LY, Zhou G, Liu K, Hu C, Zuo XC, Wang YF. Risk of non-melanoma skin cancer for rheumatoid arthritis patients receiving TNF antagonist: a systematic review and meta-analysis. Clin Rheumatol. 2020;39(3):769–78.PubMed
23.
Sathish Kumar B, Kumar A, Singh J, Hasanain M, Singh A, Fatima K, Yadav DK, Shukla V, Luqman S, Khan F, et al. Synthesis of 2-alkoxy and 2-benzyloxy analogues of estradiol as anti-breast cancer agents through microtubule stabilization. Eur J Med Chem. 2014;86:740–51.PubMed
24.
Srivastava A, Fatima K, Fatima E, Singh A, Singh A, Shukla A, Luqman S, Shanker K, Chanda D, Khan F, et al. Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity. Eur J Pharm Sci. 2020;154:105513.PubMed
25.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. Jama. 2000;283(15):2008–12.PubMed
26.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.PubMedPubMedCentral
27.
Hamid AA, Kaushal T, Ashraf R, Singh A, Chand Gupta A, Prakash O, Sarkar J, Chanda D, Bawankule DU, Khan F, et al. (22β,25R)-3β-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway. Steroids. 2017;119:43–52.PubMed
28.
Khwaja S, Fatima K, Hasanain M, Behera C, Kour A, Singh A, Luqman S, Sarkar J, Chanda D, Shanker K, et al. Antiproliferative efficacy of curcumin mimics through microtubule destabilization. Eur J Med Chem. 2018;151:51–61.PubMed
29.
Sathish Kumar B, Singh A, Kumar A, Singh J, Hasanain M, Singh A, Masood N, Yadav DK, Konwar R, Mitra K, et al. Synthesis of neolignans as microtubule stabilisers. Bioorg Med Chem. 2014;22(4):1342–54.PubMed
30.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.PubMed
31.
Hamid AA, Hasanain M, Singh A, Bhukya B, Omprakash J, Vasudev PG, Sarkar J, Chanda D, Khan F, Aiyelaagbe OO, et al. Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin. Steroids. 2014;87:108–18.PubMed
32.
Jain S, Singh A, Khare P, Chanda D, Mishra D, Shanker K, Karak T. Toxicity assessment of Bacopa monnieri L. grown in biochar amended extremely acidic coal mine spoils. Ecol Eng. 2017;108:211–9.
33.
Singh A, Fatima K, Singh A, Behl A, Mintoo MJ, Hasanain M, Ashraf R, Luqman S, Shanker K, Mondhe DM, et al. Anticancer activity and toxicity profiles of 2-benzylidene indanone lead molecule. Eur J Pharm Sci. 2015;76:57–67.PubMed
34.
Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56(9):2886–95.PubMed
35.
Solomon DH, Kremer JM, Fisher M, Curtis JR, Furer V, Harrold LR, Hochberg MC, Reed G, Tsao P, Greenberg JD. Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs. Semin Arthr Rheum. 2014;43(4):489–97.
36.
Dreyer L, Mellemkjaer L, Andersen AR, Bennett P, Poulsen UE, Juulsgaard Ellingsen T, Hansen TH, Jensen DV, Linde L, Lindegaard HM, et al. Incidences of overall and site specific cancers in TNFalpha inhibitor treated patients with rheumatoid arthritis and other arthritides—a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013;72(1):79–82.PubMed
37.
Raaschou P, Simard JF, Asker Hagelberg C, Askling J, ARTIS Study Group. 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.PubMedPubMedCentral
38.
Wadstrom H, Frisell T, Askling J, Anti-Rheumatic Therapy in Sweden (ARTIS) Study Group. Malignant neoplasms in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors, tocilizumab, abatacept, or rituximab in clinical practice: a nationwide cohort study from Sweden. JAMA Intern Med. 2017;177(11):1605–12.PubMedPubMedCentral
39.
Mercer LK, Green AC, Galloway JB, Davies R, Lunt M, Dixon WG, Watson KD, British Society for Rheumatology Biologics Register Control Centre Consortium, Symmons DP, Hyrich KL, et al. The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients with rheumatoid arthritis: longitudinal results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2012;71(6):869–74.PubMed
40.
Ozen G, Pedro S, Schumacher R, Simon TA, Michaud K. Safety of abatacept compared with other biologic and conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: data from an observational study. Arthr Res Ther. 2019;21(1):141.
41.
Long MD, Herfarth HH, Pipkin CA, Porter CQ, Sandler RS, Kappelman MD. Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2010;8(3):268–74.PubMedPubMedCentral
42.
Asgari MM, Ray GT, Geier JL, Quesenberry CP. Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population. J Am Acad Dermatol. 2017;76(4):632–8.PubMed
43.
Kimball AB, Schenfeld J, Accortt NA, Anthony MS, Rothman KJ, Pariser D. Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States. Br J Dermatol. 2015;173(5):1183–90.PubMed
44.
Haynes K, Beukelman T, Curtis JR, Newcomb C, Herrinton LJ, Graham DJ, Solomon DH, Griffin MR, Chen L, Liu L, et al. Tumor necrosis factor alpha inhibitor therapy and cancer risk in chronic immune-mediated diseases. Arthr Rheum. 2013;65(1):48–58.
45.
Jaju PD, Ransohoff KJ, Tang JY, Sarin KY. Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors. J Am Acad Dermatol. 2016;74(3):437–51 (quiz 452-434).PubMed
46.
Qureshi AA, Wei-Passanese EX, Li T, Han J. Host risk factors for the development of multiple non-melanoma skin cancers. J Eur Acad Dermatol Venereol. 2013;27(5):565–70.PubMed
47.
Jacobs JWG. Lessons for the use of non-biologic anchor treatments for rheumatoid arthritis in the era of biologic therapies. Rheumatology. 2012;51(suppl_4):iv27–33.PubMed
48.
Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, Worthy G, Landewé R, Smolen JS, Emery P, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010;69(6):976–86.PubMed
49.
Rau R. Efficacy of methotrexate in comparison to biologics in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28(5 Suppl 61):S58-64.PubMed
50.
Parida JR, Misra DP, Wakhlu A, Agarwal V. Is non-biological treatment of rheumatoid arthritis as good as biologics? World J Orthop. 2015;6(2):278–83.PubMedPubMedCentral
51.
Lluch P, Urruticoechea A, Lluch J, Moll MC, Matos M, Benet JM, Ene L, Cañete JD. Development of leprosy in a patient with rheumatoid arthritis during treatment with etanercept: a case report. Semin Arthr Rheum. 2012;42(2):127–30.
52.
Chiu YM, Chen DY. Infection risk in patients undergoing treatment for inflammatory arthritis: non-biologics versus biologics. Expert Rev Clin Immunol. 2020;16(2):207–28.PubMed
53.
Lo B, Zhao M, Vind I, Burisch J. The risk of extraintestinal cancer in inflammatory bowel disease: a systematic review and meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol. 2021;19(6):1117–38.PubMed
54.
Singh A, Mohanty I, Singh J, Rattan S. BDNF augments rat internal anal sphincter smooth muscle tone via RhoA/ROCK signaling and nonadrenergic noncholinergic relaxation via increased NO release. Am J Physiol Gastrointest Liver Physiol. 2020;318(1):G23–33.PubMed
55.
Solitano V, D’Amico F, Correale C, Peyrin-Biroulet L, Danese S. Thiopurines and non-melanoma skin cancer: partners in crime in inflammatory bowel diseases. Br Med Bull. 2020;136(1):107–17.PubMed
56.
Leiter U, Eigentler T, Garbe C. Epidemiology of skin cancer. Adv Exp Med Biol. 2014;810:120–40.PubMed
57.
Waters JP, Pober JS, Bradley JR. Tumour necrosis factor in infectious disease. J Pathol. 2013;230(2):132–47.PubMed
58.
Korhonen R, Moilanen E. Abatacept, a novel CD80/86-CD28 T cell co-stimulation modulator, in the treatment of rheumatoid arthritis. Basic Clin Pharmacol Toxicol. 2009;104(4):276–84.PubMed
59.
Blair HA, Deeks ED. Abatacept: a review in rheumatoid arthritis. Drugs. 2017;77(11):1221–33.PubMed
60.
Tavakolpour S, Alesaeidi S, Darvishi M, GhasemiAdl M, Darabi-Monadi S, Akhlaghdoust M, Elikaei Behjati S, Jafarieh A. A comprehensive review of rituximab therapy in rheumatoid arthritis patients. Clin Rheumatol. 2019;38(11):2977–94.PubMed
61.
Bachelet T, Visentin J, Davis P, Taton B, Guidicelli G, Kaminski H, Merville P, Couzi L. The incidence of post-transplant malignancies in kidney transplant recipients treated with Rituximab. Clin Transpl. 2021;35(2):e14171.
62.
63.
Calip GS, Patel PR, Adimadhyam S, Xing S, Wu Z, Sweiss K, Schumock GT, Lee TA, Chiu BCH. Tumor necrosis factor-alpha inhibitors and risk of non-Hodgkin lymphoma in a cohort of adults with rheumatologic conditions. Int J Cancer. 2018;143(5):1062–71.PubMedPubMedCentral
64.
Nebbia M, Yassin NA, Spinelli A. Colorectal cancer in inflammatory Bowel disease. Clin Colon Rectal Surg. 2020;33(5):305–17.PubMedPubMedCentral
65.
Söderlund S, Brandt L, Lapidus A, Karlén P, Broström O, Löfberg R, Ekbom A, Askling J. Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease. Gastroenterology. 2009;136(5):1561–7 (quiz 1818-1569).PubMed
Metadata
Title
Risk of non-melanoma skin cancer with biological therapy in common inflammatory diseases: a systemic review and meta-analysis
Authors
Ruolin Liu
Qianyi Wan
Rui Zhao
Haitao Xiao
Ying Cen
Xuewen Xu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02325-9

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