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PloS One 2016Three checkpoint inhibitor drugs have been approved by the US Food and Drug Administration for use in specific types of cancers. While the results are promising, severe... (Review)
Review
BACKGROUND
Three checkpoint inhibitor drugs have been approved by the US Food and Drug Administration for use in specific types of cancers. While the results are promising, severe immunotherapy-related adverse events (irAEs) have been reported.
OBJECTIVES
To conduct a systematic review of case reports describing the occurrence of irAEs in patients with cancer following checkpoint blockade therapy, primarily to identify potentially unrecognized or unusual clinical findings and toxicity.
DATA SOURCES
We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane CENTRAL with no restriction through August 2015.
STUDY SELECTION
Studies reporting cases of cancer develop irAEs following treatment with anti CTLA-4 (ipilimumab) or anti PD-1 (nivolumab or pembrolizumab) antibodies were included.
DATA EXTRACTION
We extracted data on patient characteristics, irAEs characteristics, how irAEs were managed, and their outcomes.
DATA SYNTHESIS
191 publications met inclusion criteria, reporting on 251 cases. Most patients had metastatic melanoma (95.6%), and the majority were treated with ipilimumab (93.2%). Autoimmune colitis, hepatitis, endocrinopathies, and cutaneous irAEs were the most frequently reported irAEs in ipilimumab treated patients. A broad spectrum of toxicities were reported for almost every body system. Moreover, well-defined diseases such as sarcoidosis, polyarthritis, polymyalgia rheumatica/arteritis, lupus, celiac disease, dermatomyositis, and Vogt-Koyanagi-like syndrome were reported. The most frequent irAEs reported with anti-PD1 agents were dermatitis for pembrolizumab, and thyroid disease and pneumonitis for nivolumab. Complete resolution of adverse events occurred in most cases. However, persistent irAEs and death were reported, mainly in patients treated with ipilimumab.
LIMITATIONS
Our study is limited by information available in the original reports.
CONCLUSIONS
Evidence from case reports shows that cancer patients develop irAEs following checkpoint blockade therapy, and can occasionally develop clearly defined autoimmune systemic diseases. While discontinuation of therapy and/or treatment can result in resolution of irAEs, long-term sequelae and death have been reported.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cell Cycle Checkpoints; Female; Humans; Male; Middle Aged; Neoplasms
PubMed: 27472273
DOI: 10.1371/journal.pone.0160221 -
PloS One 2016Interstitial lung disease (ILD) is an extramuscular manifestation that results in increased morbidity and mortality from polymyositis (PM) and dermatomyositis (DM). The... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Interstitial lung disease (ILD) is an extramuscular manifestation that results in increased morbidity and mortality from polymyositis (PM) and dermatomyositis (DM). The aim of this study was to systematically evaluate risk factors associated with the development of ILD in PM/DM.
METHODS
Observational studies were identified from searching PubMed, Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between risk factors and ILD in PM/DM using either fixed- or random-effects models, whichever were appropriate. Heterogeneity tests, sensitivity analyses, and publication bias assessments were also performed.
RESULTS
Twenty-three studies were selected for a meta-analysis that included 834 patients and 1245 control subjects. Risk factors that may have increased the risk of developing ILD in PM/DM patients included older age at diagnosis (SMD, 0.35; 95% CI, 0.18-0.52; P < 0.0001), arthritis/arthralgia (OR, 3.17; 95% CI, 1.99-5.04; P < 0.00001), fever (OR, 2.31; 95% CI, 1.42-3.76; P = 0.0007), presence of anti-Jo-1 antibodies (OR, 3.34; 95% CI, 2.16-5.16; P < 0.00001), elevated erythrocyte sedimentation rate (ESR; SMD, 0.48; 95% CI, 0.32-0.64; P < 0.00001), presence of anti-MDA5 antibodies (OR, 18.26; 95% CI, 9.66-34.51; P < 0.00001), and elevated C-reactive protein level (CRP; OR, 3.50; 95% CI, 1.48-8.28; P = 0.004). Meanwhile, malignancy (OR, 0.36; 95% CI, 0.18-0.72; P = 0.004) reduced the risk of developing ILD in PM/DM patients.
CONCLUSION
Our meta-analysis results suggest that the association between PM/DM and ILD may be due to such risk factors as older age at diagnosis, arthritis/arthralgia, fever, presence of anti-Jo-1 antibodies, elevated ESR, presence of anti-MDA5 antibodies, and elevated CRP level, while malignancy was associated with a reduced risk of developing ILD. Thus, these variables may be used to guide screening processes for ILD in patients with PM/DM.
Topics: Demography; Dermatomyositis; Female; Humans; Lung Diseases, Interstitial; Male; Polymyositis; Publication Bias; Risk Factors
PubMed: 27171228
DOI: 10.1371/journal.pone.0155381 -
International Braz J Urol : Official... 2016Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer... (Review)
Review
BACKGROUND
Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility.
MATERIALS AND METHODS
A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases.
RESULTS
A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies.
CONCLUSIONS
Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.
Topics: Alkylating Agents; Behcet Syndrome; Dermatomyositis; Gout; Humans; Infertility, Male; Lupus Erythematosus, Systemic; Male; Rheumatic Diseases; Spondylitis, Ankylosing
PubMed: 27120778
DOI: 10.1590/S1677-5538.IBJU.2014.0595