scholarly journals Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events

2020 ◽  
Vol 35 (12) ◽  
pp. 2331-2338
Author(s):  
Vera E. R. Asscher ◽  
◽  
Quirine van der Vliet ◽  
Karen van der Aalst ◽  
Anniek van der Aalst ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Adverse Events ◽  
Older Patients ◽  
Tumor Necrosis ◽  
Patient Age ◽  
Younger Patients ◽  
Patient Âgé ◽  
Serious Infections ◽  
Severe Adverse Events ◽  
Necrosis Factor

Abstract Purpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. Methods Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. Results In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185–12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098–9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248–66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. Conclusion Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

scholarly journals Safety of Anti-Tumor Necrosis Factor Therapies in Arthritis Patients

2014 ◽  
Vol 17 (3) ◽  
pp. 324 ◽  
Author(s):  
Radu M Nanau ◽  
Manuela G Neuman
Keyword(s):  
Tumor Necrosis Factor ◽  
Liver Injury ◽  
Adverse Events ◽  
Tumor Necrosis ◽  
Certolizumab Pegol ◽  
Therapeutic Area ◽  
Drug Induced ◽  
Rheumatic Arthritis ◽  
Drug Induced Liver Injury ◽  
Necrosis Factor

Purpose. Inflammatory and rheumatic arthritis remain leading causes of disability worldwide. The arthritis therapeutic area commands the largest market for the prescription of biological and non-steroidal anti-inflammatory drugs (NSAID). Yet biotechnology and pharmaceutical companies conducting research and providing therapeutics in this area frequently face challenges in patient safety.  The purpose of our study was to assess safety of anti-tumor necrosis factor therapies in arthritis patients.  Methods: The present study systematically reviews adverse events of biologicals alone or in the presence of NSAIDs and other immunosuppressant therapeutics such as disease-modifying antirheumatic drugs (DMARD). We assessed the rheumatology literature that included clinical trials with anti-tumor necrosis factor (TNF) biologicals and case reports published between 2010 and 2014.  Results: Currently approved anti-TNF biologicals in arthritis include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab, and the fusion protein etanercept. The most frequently-reported adverse event was infection. We grouped the adverse reactions as immune-mediated, hypersensitivity syndrome reactions including cutaneous and hepatic manifestation, neurological, hematological, and malignancy.  Discussion: Most adverse events are due to the failure of host immunological control, which involves susceptibility to the drug itself, or de novo infection or reactivation of a latent bacterial or viral infection, often with a different expression of disease. Drug-induced liver injury associated with anti-TNF biologicals must be kept in mind when evaluating patients with increased liver enzymes.  Conclusion: Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving a personalized medicine approach to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert of anti-TNF agents as potential causes of drug-induced liver injury and monitor the therapies. Personalizing therapeutic pharmacovigilance promises to optimize benefits while minimizing side effects.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Safety, Tolerability, and Clinical Outcomes after Intraarticular Injection of a Recombinant Adeno-associated Vector Containing a Tumor Necrosis Factor Antagonist Gene: Results of a Phase 1/2 Study

2009 ◽  
Vol 37 (4) ◽  
pp. 692-703 ◽  
Author(s):  
PHILIP J. MEASE ◽  
NATHAN WEI ◽  
EDWARD J. FUDMAN ◽  
ALAN J. KIVITZ ◽  
JOY SCHECHTMAN ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Tumor Necrosis ◽  
Phase 1 ◽  
Open Label ◽  
Disseminated Histoplasmosis ◽  
Patient Reported ◽  
Dose Dependent ◽  
Necrosis Factor

Objective.To assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene.Methods.In this phase 1/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 × 1011, 1 × 1012, or 1 × 1013DNase-resistant particles/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12–30 weeks later, depending on when the target joint met predetermined criteria for reinjection.Results.127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14).Conclusion.IA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients.

A Safety Assessment of Tumor Necrosis Factor Antagonists During Pregnancy: A Review of the Food and Drug Administration Database

2009 ◽  
Vol 36 (3) ◽  
pp. 635-641 ◽  
Author(s):  
JOHN D. CARTER ◽  
ANIL LADHANI ◽  
LOUIS R. RICCA ◽  
JOANNE VALERIANO ◽  
FRANK B. VASEY
Keyword(s):  
Congenital Anomaly ◽  
Tumor Necrosis Factor ◽  
Adverse Events ◽  
Drug Administration ◽  
Congenital Anomalies ◽  
Tumor Necrosis ◽  
Food And Drug Administration ◽  
Tnf Antagonists ◽  
Historical Controls ◽  
Necrosis Factor

Objective.To present any congenital anomalies with respect to tumor necrosis factor (TNF) antagonists reported to the US Food and Drug Administration (FDA) to determine if there are common findings.Methods.A review of the FDA database of reported adverse events with etanercept, infliximab, and adalimumab from 1999 through December of 2005 was performed. Key words for congenital anomalies were employed as search tools. Duplicate reports were eliminated. Any concomitant medicines were recorded.Results.Our review of > 120,000 adverse events revealed a total of 61 congenital anomalies in 41 children born to mothers taking a TNF antagonist. Of these mothers, 22 took etanercept and 19 took infliximab. There were no reports in women taking adalimumab. The most common reported congenital anomaly was some form of heart defect. Twenty-four of the 41 (59%) children had one or more congenital anomalies that are part of vertebral abnormalities, anal atresia, cardiac defect, tracheoesophageal, renal, and limp abnormalities (VACTERL) association. There were 34 specific types of congenital anomalies in total, and 19 (56%) of those are part of the VACTERL spectrum. Nine of these 19 (47%) types of VACTERL anomalies were observed statistically significantly more than historical controls (p < 0.01); in 4 of these 9 the p value was ≤ 0.0001. Thirteen (32%) of the children had more than one congenital anomaly; 7 of these 13 children had 2 defects that are part of the VACTERL spectrum. However, only 1 child was diagnosed with VACTERL. In 24/41 cases (59%) the mother was taking no other concomitant medications.Conclusion.A seemingly high number of congenital anomalies that are part of the VACTERL spectrum have been reported. These congenital anomalies are occurring at a rate higher than historical controls. This commonality raises concerns of a possible causative effect of the TNF antagonists.

Sign in / Sign up

Export Citation Format

Share Document