Response letter to comments on “Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta‐analysis”

Abstract Abstract 5120 Background: Bortezomib (VELCADE) is the first proteasome inhibitor to be approved by regulatory agencies for treatment of multiple myeloma and mantle cell lymphoma. Maculopapular rash is a common, adverse event to bortezomib. Because the summary incidence of bortezomib-induced skin rash is not well known, we performed a systematic literature review and meta-analysis to determine the incidence and overall risk. Methods: We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology and The American Society of Hematology annual meetings from 1998 to July 2011, to identify relevant clinical studies. Eligible studies included prospective clinical phase II and phase III trials, with data on the incidence of rash in patients taking 1.3mg/m2, 1.5mg/m2, or 1.6 mg/m2 of bortezomib twice weekly for two weeks followed by one week off, in a 21-day cycle. The incidence of rash and relative risk (RR) were calculated using random-effects or fixed-effects model, depending on the heterogeneity of included studies. Results: A total of 2,469 patients with various hematologic and solid malignancies from 32 clinical trials were included for analysis. Among patients receiving bortezomib, the summary incidences of all-grade and high-grade rash were 18.8 % (95% CI: 14.9% to 23.5%) and 3.6 % (95% CI: 2.3% to 5.7%), respectively. We found no significant increase in rash incidence with higher doses of bortezomib. In addition, bortezomib was associated with an increased risk in both all grade (RR:19.703, 95% CI: 8.734 to 44.446, p<0.001) and high-grade rash (RR: 5.354, 95% CI: 2.158 to 13.285, p<0.001), in comparison with controls. Conclusion: Bortezomib is associated with a significant risk of developing rash. Management of bortezomib-induced rash is critical to prevent a negative effect on quality of life and dose modifications, both of which may affect clinical outcome. Disclosures: Wu: Onyx: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Genentech: Speakers Bureau. Gerecitano:Millenium: Research Funding.

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Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210708 ◽

2017 ◽

Vol 76 (6) ◽

pp. 1101-1136 ◽

Cited By ~ 153

Author(s):

Sofia Ramiro ◽

Alexandre Sepriano ◽

Katerina Chatzidionysiou ◽

Jackie L Nam ◽

Josef S Smolen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Literature Review ◽

Systematic Literature Review ◽

Observational Studies ◽

Meta Analysis ◽

Risk Of Bias ◽

Eligibility Criteria ◽

Increased Risk ◽

Serious Infections ◽

Safety Outcomes

ObjectivesTo assess the safety of synthetic (s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) for the management of rheumatoid arthritis (RA) to inform the European League Against Rheumatism recommendations for the management of RA.MethodsSystematic literature review (SLR) of observational studies comparing any DMARD with another intervention for the management of patients with RA. All safety outcomes were included. A comparator group was required for the study to be included. Risk of bias was assessed with the Hayden's tool.ResultsTwenty-six observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria (15 on serious infections, 4 on malignancies). Substantial heterogeneity precluded meta-analysis. Together with the evidence from the 2013 SLR, based on 15 studies, 7 at low risk of bias, patients on bDMARDs compared with patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1 to 1.8)—without differences across bDMARDs—a higher risk of tuberculosis (aHR 2.7 to 12.5), but no increased risk of infection by herpes zoster. Patients on bDMARDs did not have an increased risk of malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5).ConclusionsThese findings confirm the known safety pattern of bDMARDs, including both tumour necrosis factor-α inhibitor (TNFi) and non-TNFi, for the treatment of RA.

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POS0641 INCIDENCE OF GASTRO-INTESTINAL COMPLICATIONS IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING BIOLOGICAL DMARDS IN OBSERVATIONAL COHORT STUDIES: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3755 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 559.1-559

Author(s):

A. Charlotte ◽

D. Jerome ◽

C. Lukas ◽

C. Rempenault ◽

A. Constantin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Literature Review ◽

Cohort Studies ◽

Systematic Literature Review ◽

Meta Analysis ◽

Tnf Inhibitors ◽

Gi Tract ◽

Biological Dmards ◽

Increased Risk ◽

Observational Cohort

Background:Rheumatoid arthritis (RA) patients are at increased risk of gastro-intestinal (GI) perforations compared with non-RA patients, resulting in increased mortality. Clinical trials, post-marketing studies and registries have reported an increased risk of GI perforations in RA patients treated with tocilizumab.Objectives:The aim of our study was to assess the incidence of GI complications among RA patients receiving bDMARDs in observational cohort studiesMethods:A systematic literature review was carried out through September 2020 on the Pubmed, Embase and international congress databases, selecting observational cohort studies assessing the incidence of GI complications, including perforations and diverticulitis, in RA patients receiving bDMARDS. Keywords were “gastrointestinal perforation”, “gastrointestinal disease”, “diverticulitis”, “biological DMARDs” and “rheumatoid arthritis” with no publication date limit. Studies were selected independently by two readers. Data were extracted by one investigator and independently checked by another. A meta-analysis was performed with Review Manager Software, with random-effects models, whenever methodologically possible and relevant.Results:The literature search revealed 232 articles and abstracts of potential interest, and further examination resulted in 7 studies fulfilling required criteria. Among bDMARDs, Tocilizumab was associated with an increased incidence of GI perforations, with an overall incidence of 2.40 per 1000 person-years (95% confidence interval [95% CI] 1.45-3.35). The overall incidences of GI perforations were 1.01 per 1000 PY [0.75-1.27] for TNF inhibitors, 1.07 per 1000 PY [0.53-1.62] for abatacept and 1.12 per 1000 PY [0.16-2.08] for rituximab (Figure 1). In RA patients treated with tocilizumab, most of the perforations were located in the lower GI tract, with an incidence of 2.24 per 1000 PY [1.24-3.52]. The incidences of upper GI perforations were similar across the different bDMARDs. The incidences of diverticulitis were 4.99 per 1000 PY [4.08-5.99] in RA patients receiving tocilizumab and 1.81 per 1000 PY [1.47-2.19] in those receiving TNF inhibitors.Figure 1.Meta-analysis of the incidences of gastro-intestinal perforations in RA patients receiving bDMARDs in observational cohort studiesConclusion:In our meta-analysis, focused in RA patients receiving bDMARDs in observational cohort studies, tocilizumab was associated with an increased incidence of GI perforations, mainly located in the lower GI tract. An history of diverticulitis and long-term corticosteroid therapy were associated with an increased risk of GI perforations.Acknowledgements:We cannot express enough thanks to PhD Constantin and PhD Morel for their support and encouragement.We would like to address a special word of thanks to PhD Lukas for his accuracy.Special Thanks to Claire Rempenault for her precious advices. You have been a role model for us.Disclosure of Interests:None declared

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