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

ABSTRACT: 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.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 1 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 the pooled incidence rates as well as risk differences between the various treatments.Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow-up evaluation after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8 per 1000 p-y), immune-modulator therapy (36.2 per 1000 p-y), or no immunosuppression (37.5 per 1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5 per 1000 p-y) (P > .1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease showed 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 per 1000 p-y for immune-modulatory agents and 43.7 per 1000 p-y for anti-TNF agents) vs more than 6 years after the index cancer (32.9 per 1000 p-y for immune-modulatory agents, P = .86; and 21.0 per 1000 p-y for anti-TNF agents, P = .43).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.

SUBMITTER: Shelton E

PROVIDER: S-EPMC4925196 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Shelton Edward E Laharie David D Scott Frank I FI Mamtani Ronac R Lewis James D JD Colombel Jean-Frederic JF Ananthakrishnan Ashwin N AN

Gastroenterology 20160401 1

<h4>Background & aims</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27039969

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Project description:ObjectivesThe treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates.MethodsElectronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes.ResultsTwenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I2 = 90%) as compared to a single dose (69.3, 52.4-82.3, I2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I2 = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I2 = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I2 = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy.ConclusionSeroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

Project description:BackgroundAlthough surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical therapy in preventing recurrence of endometriosis following surgery.Objective and rationaleWe performed a review of prospective observational studies and randomised controlled trials (RCTs) to evaluate the risk of endometriosis recurrence in patients undergoing post-operative hormonal suppression, compared to placebo/expectant management.Search methodsThe following databases were searched from inception to March 2020 for RCTs and prospective observational cohort studies: MEDLINE, Embase, Cochrane CENTRAL and Web of Science. We included English language full-text articles of pre-menopausal women undergoing conservative surgery (conserving at least one ovary) and initiating hormonal suppression within 6 weeks post-operatively with either combined hormonal contraceptives (CHC), progestins, androgens, levonorgesterel-releasing intra-uterine system (LNG-IUS) or GnRH agonist or antagonist. We excluded from the final analysis studies with <12 months of follow-up, interventions of diagnostic laparoscopy, experimental/non-hormonal treatments or combined hormonal therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies.OutcomesWe included 17 studies (13 RCTs and 4 cohort studies), with 2137 patients (1189 receiving post-operative suppression and 948 controls), which evaluated various agents: CHC (6 studies, n = 869), progestin (3 studies, n = 183), LNG-IUS (2 studies, n = 94) and GnRH agonist (9 studies, n = 1237). The primary outcome was post-operative endometriosis recurrence, determined by imaging or recurrence of symptoms, at least 12 months post-operatively. The secondary outcome was change in endometriosis-related pain. Mean follow up of included studies ranged from 12 to 36 months, and outcomes were assessed at a median of 18 months. There was a significantly decreased risk of endometriosis recurrence in patients receiving post-operative hormonal suppression compared to expectant management/placebo (relative risk (RR) 0.41, 95% CI: 0.26 to 0.65), 14 studies, 1766 patients, I2 = 68%, random effects model). Subgroup analysis on patients treated with CHC and LNG-IUS as well as sensitivity analyses limited to RCTs and high-quality studies showed a consistent decreased risk of endometriosis recurrence. Additionally, the patients receiving post-operative hormonal suppression had significantly lower pain scores compared to controls (SMD -0.49, 95% CI: -0.91 to -0.07, 7 studies, 652 patients, I2 = 68%).Wider implicationsHormonal suppression should be considered for patients not seeking pregnancy immediately after endometriosis surgery in order to reduce disease recurrence and pain. Various hormonal agents have been shown to be effective, and the exact treatment choice should be individualised according to each woman's needs.

Project description:BACKGROUND & AIMS:Management of immune-mediated inflammatory diseases often requires lifelong immunosuppression. Increasing numbers of older patients have inflammatory diseases and are particularly vulnerable to risks of immune suppressive therapies-particularly infections and malignancies. METHODS:We systematically searched PubMed/Medline and Embase to identify eligible studies that examined the safety of biologic therapies in older patients with immune-mediated inflammatory diseases (inflammatory bowel disease, rheumatoid arthritis, psoriasis). Included studies provided information on patients who began receiving therapy with a biologic agent when they were older than 60 years and a control population (either younger users of biologics or older patients who did not use biologics). Information of on overall pooled rates of infections, malignancy, and mortality were extracted. A DerSimonian and Laird random effects model was used to calculate pooled odds ratios (ORs) and 95% CIs. RESULTS:Our meta-analysis included 14 unique studies that comprised 4719 older users of biologics, 13,305 younger users of biologics, and 3961 older patients who did not use biologics. The pooled prevalence of infections in older and younger users of biologics was 13% and 6% respectively, yielding a pooled random effects odds ratio of 2.28 (95% CI, 1.57-3.31). Older age was associated with a significant increase in risk of malignancy (OR, 3.07; 95% CI, 1.98-4.62) compared to younger age. Older users of biologics had a 3-fold increase in risk of infection compared to patients who did not use biologics (OR, 3.60; 95% CI, 1.62-8.01), but there were no significant differences in odds of malignancy (0.54, 95% CI, 0.28-1.05) or death (OR, 1.52; 95% CI, 0.44-5.28) compared to older patients who did not use biologics. CONCLUSION:In a systematic review and meta-analysis of studies on the safety of biologic therapies in older patients with inflammatory diseases, we found that older users of biologic agents have an increased risk of infections compared with younger users or older patients who do not use biologics. Large, prospective cohort studies are needed to examine safety of biologic therapy in older patients with immune-mediated diseases.

Dataset Information

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

Publications

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

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