Background/Introduction: Chronic inflammation might be a risk factor for lymphoma [1]. However, at variance with rheumatoid arthritis (RA), the evidence supporting an association of inflammatory bowel diseases (IBDs) with the development of lymphoma is still scarce. Some authors suggested that pharmacological treatments for IBDs and RA, e.g. anti-tumor necrosis factor (anti-TNF) drugs, could promote the development of lymphoma [2, 3]. However, the association of the use of anti-TNF agents with the development of lymphoma is still undetermined. Aim: We analyzed studies aimed at assessing the association between the use of anti-TNF drugs and lymphoma in IBD patients. Methods: This systematic review was performed according with MOOSE and PRISMA statements. The literature search was conducted by examining MEDLINE, EMBASE, and Google Scholar for all indexed articles published in English language from January 1st, 1999 to June 30th, 2018. We included observational studies conducted on IBD patients and focused on at least one of four anti-TNF drugs (i.e. infliximab, adalimumab, certolizumab pegol and golimumab). From each selected study, source used to collect patient clinical data, design and main methodologic characteristics (e.g. adjustments and matchings, lag period, prevalent patients, observation period, patient disease [Crohn’s disease, ulcerative colitis or IBD], and drug exposure) were extracted. An assessment of the methodologic shortcomings of the selected studies was performed. Results: Among 41 selected full-text articles, 14 studies met the eligibility criteria and were included in the review. Only four studies found a significant association of anti-TNF drugs with lymphoma or groups of cancers including lymphoma. However, the important methodologic issues of all the included studies made their results unreliable, irrespectively of whether their findings supported an association or not. The identified shortcomings included lack of lag period, inclusion of prevalent patients, time-window bias or immortal- time bias. Conclusions: The widespread implementation of computer-based health databases has encouraged the conduction of observational studies. However, no cautions for managing adequately the methodologic underlying such investigations are usually taken, leading to an explosion of the publication of poorly conceived studies and analytic designs that have generated incorrect or unreliable conclusions on the safety of exposure to drugs. The results of the present systematic review are fully in line with this trend. Current evidence from observational studies does not allow excluding or confirming an association of the exposure to anti-TNF treatments with lymphoma in IBD patients. Additional well-designed observational studies are warranted to provide a conclusive answer to this relevant question.
Anti-tumor Necrosis Factor Drugs and Risk of Lymphoma in Patients with Inflammatory Bowel Disease
Blandizzi, C;Tuccori, M;Ferraro, S;Leonardi, L;Convertino, I
2019-01-01
Abstract
Background/Introduction: Chronic inflammation might be a risk factor for lymphoma [1]. However, at variance with rheumatoid arthritis (RA), the evidence supporting an association of inflammatory bowel diseases (IBDs) with the development of lymphoma is still scarce. Some authors suggested that pharmacological treatments for IBDs and RA, e.g. anti-tumor necrosis factor (anti-TNF) drugs, could promote the development of lymphoma [2, 3]. However, the association of the use of anti-TNF agents with the development of lymphoma is still undetermined. Aim: We analyzed studies aimed at assessing the association between the use of anti-TNF drugs and lymphoma in IBD patients. Methods: This systematic review was performed according with MOOSE and PRISMA statements. The literature search was conducted by examining MEDLINE, EMBASE, and Google Scholar for all indexed articles published in English language from January 1st, 1999 to June 30th, 2018. We included observational studies conducted on IBD patients and focused on at least one of four anti-TNF drugs (i.e. infliximab, adalimumab, certolizumab pegol and golimumab). From each selected study, source used to collect patient clinical data, design and main methodologic characteristics (e.g. adjustments and matchings, lag period, prevalent patients, observation period, patient disease [Crohn’s disease, ulcerative colitis or IBD], and drug exposure) were extracted. An assessment of the methodologic shortcomings of the selected studies was performed. Results: Among 41 selected full-text articles, 14 studies met the eligibility criteria and were included in the review. Only four studies found a significant association of anti-TNF drugs with lymphoma or groups of cancers including lymphoma. However, the important methodologic issues of all the included studies made their results unreliable, irrespectively of whether their findings supported an association or not. The identified shortcomings included lack of lag period, inclusion of prevalent patients, time-window bias or immortal- time bias. Conclusions: The widespread implementation of computer-based health databases has encouraged the conduction of observational studies. However, no cautions for managing adequately the methodologic underlying such investigations are usually taken, leading to an explosion of the publication of poorly conceived studies and analytic designs that have generated incorrect or unreliable conclusions on the safety of exposure to drugs. The results of the present systematic review are fully in line with this trend. Current evidence from observational studies does not allow excluding or confirming an association of the exposure to anti-TNF treatments with lymphoma in IBD patients. Additional well-designed observational studies are warranted to provide a conclusive answer to this relevant question.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
