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

Scott, Frank I.; Mamtani, Ronac; Brensinger, Colleen M.; Haynes, Kevin; Chiesa-Fuxench, Zelma C.; Zhang, Jie; Chen, Lang; Xie, Fenglong; Yun, Huifeng; Osterman, Mark T.; Beukelman, Timothy; Margolis, David J.; Curtis, Jeffrey R.; Lewis, James D.

doi:10.1001/jamadermatol.2015.3029

Cited by 136 publications

(120 citation statements)

References 47 publications

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“…Eleven articles represented duplicate data 47–52 and we were unable to obtain sufficient information for analysis from 5 studies 53–57 resulting in a final cohort of 16 unique studies 34–43, 46, 58–62 (Table 1). There was an equal number of studies in IBD 35, 39–42, 46, 58 and RA 34, 36, 37, 43, 60–62 , with 1 study combining both populations 59 and 1 study in psoriasis 62 . Ten studies were population-based 34–38, 43, 46, 59, 60, 62 and 12 studies adopted a cohort design 34–38, 40, 41, 43, 46, 59, 60, 62 .…”

Section: Resultsmentioning

confidence: 99%

“…There was an equal number of studies in IBD 35, 39–42, 46, 58 and RA 34, 36, 37, 43, 60–62 , with 1 study combining both populations 59 and 1 study in psoriasis 62 . Ten studies were population-based 34–38, 43, 46, 59, 60, 62 and 12 studies adopted a cohort design 34–38, 40, 41, 43, 46, 59, 60, 62 . Three were from North America 40, 58, 59 , twelve from Europe 34–39, 41–43, 46, 60, 62 , and one from Asia 61 .…”

Section: Resultsmentioning

confidence: 99%

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Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

et al. 2016

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Background & Aims Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy for these patients. Published studies have been small with few events, precluding robust estimates of risk. Methods We searched Medline, EMBASE, and conference proceedings for terms related to immune mediated disease, immune-suppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of patients with inflammatory bowel disease, and of patients with psoriasis) and stratified studies by type of immune-suppressive therapy (monoclonal antibodies to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no immune suppression). A random effects meta-analysis was performed to calculate pooled incidence rates as well as risk differences between the various treatments. Results Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow up after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8/1000 p-y), immune-modulator therapy (36.2/1000 p-y), or no immunosuppression (37.5/1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5/1000 p-y) (P>.1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease revealed similar results, with no increase in risk. We found similar pooled incidence values for new or primary cancers when immunosuppression was initiated within 6 years (33.6/1000 p-y for immune-modulatory agents and 43.7/1000 p-y for anti-TNF agents) vs more 6 years after the index cancer (32.9/1000 p-y for immune-modulatory agents; P=.86 and 21.0/1000 p-y for anti-TNF agents; P=.43) Conclusion In a meta-analysis of 16 studies, we observed similar rates of cancer recurrence among individuals with prior cancer who received no immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination treatments. Prospective studies are needed to ascertain optimal intervals for re-initiation of immune suppressive therapies for individuals with specific cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

et al. 2016

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“…In the present case, the combination therapy of adalimumab and methotrexate for psoriatic arthritis was discontinued when pancytopenia was detected because of the possibility of developing adverse events such as hematological malignancies. Indeed, monotherapy with anti-tumor necrosis factor (TNF)-α antagonists or methotrexate is known to increase the risk for melanomatous and non-melanomatous skin cancers, but its risk for hematological disorders, such as MDS and lymphoproliferative diseases, is not clear [18]. Moreover, a recent metaanalysis on patients who were given immunosuppressive therapy for immuno-mediated diseases after a prior malignancy showed that the incidence rates of new primary cancer (i.e., skin cancer, melanoma, hematological malignancy, breast and solid cancers) were not significantly different among patients who did not receive immunosuppression, those who receive anti-TNF-α antagonists and those who received conventional immunosuppression with thiopurines and methotrexate [19].…”

Section: Discussionmentioning

confidence: 99%

Trisomy 8-Associated Intestinal Behcet’s Disease That Achieved Complete Remission With Mesalazine

et al. 2018

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A 39-year-old man was referred to our hospital because of ileocecal ulcer and pancytopenia. Past medical history included psoriatic arthritis and acne vulgaris. Physical examination findings showed recurrent oral ulcerations and acneiform eruptions on his body. Colonoscopy confirmed the presence of an ulcer at the ileocecal valve. Human leukocyte antigen was positive for B51. Based on the bone marrow findings of hypercellularity accompanied by trilineage dysplastic changes and cytogenetic findings of 47,XY,dup(1)(q21q32), idem+8, a definite diagnosis of intestinal Behcet's disease (BD), incomplete type, associated with myelodysplastic syndrome (MDS) with positivity for trisomy 8 was finally confirmed. Treatment of intestinal BD with mesalazine at 3,000 mg daily induced complete ulcer healing after 4 months. Thereafter, two cycles of azacytidine was administered, followed by bone marrow transplantation. The patient has done well with continuous healing of the ulcer for a year. Differentiating episodic MDS with positivity for trisomy 8 from drug-induced MDS by examination of the bone marrow and the cytogenetic changes is indispensable. Intestinal BD patients who develop pancytopenia would probably need sufficient doses of mesalazine for treatment.

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“…Several earlier retrospective studies employing large healthcare and insurance databases did fuel such concerns, showing statistically significant increased risks of lymphoma, melanoma, and non-melanoma skin cancer. 66,146,147 Conversely, the prospectively collected Crohn’s Therapy, Resource, and Evaluation Assessment Tool (TREAT ™ ) Registry showed no difference in overall malignancy incidence between infliximab treated and general populations. 148 Moreover, Nyboe Anderson and colleagues demonstrated similar findings from a nationwide Danish cohort that included over 56,000 IBD patients who were followed for 489,433 person-years (PY).…”

Section: Biologicsmentioning

confidence: 99%

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease

Cohn

Dave

Loftus

2017

Inflammatory Bowel Diseases

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Ulcerative colitis and Crohn’s disease are chronic inflammatory bowel diseases for which there are no cures. These diseases are immunopathogenic, and medical treatment is centered on the temperance of a dysregulated immune response to allow mucosal healing and prevent the sequelae of fistulation and stenosis. Accordingly, the armamentarium of medications, which has expanded immensely in recent history, is not without significant infectious and neoplastic risks. Many of these untoward effects can be mitigated by screening and avoidance of contraindicated medications. This review seeks to highlight the cautions for use of immunomodulators, anticytokine and α4-integrin antagonists. The potential adverse events are further complicated by substantial heterogeneity in disease phenotype in the IBD population. Large patient registries and databases provide considerable experience and knowledge to calculate the incidence of safety outcomes. To identify rarer outcomes after prolonged therapy, more prospective studies and continued adverse event reporting will aid safe application and minimize potential harms.

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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

Cited by 136 publications

References 47 publications

Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

Trisomy 8-Associated Intestinal Behcet’s Disease That Achieved Complete Remission With Mesalazine

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease

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