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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 -
American Journal of Ophthalmology Jun 2018To review and summarize evidence in the medical literature regarding the use of pars plana vitrectomy in the management of uveitis.
PURPOSE
To review and summarize evidence in the medical literature regarding the use of pars plana vitrectomy in the management of uveitis.
DESIGN
Systematic literature review.
METHODS
A systematic literature search was conducted for relevant articles on pars plana vitrectomy for the management of uveitis. Results from the studies were compiled and analyzed.
RESULTS
Thirty-four articles, published from 2005 through 2014, were included in the final data analysis. Thirty-two manuscripts were from retrospective case series and 2 manuscripts were from randomized pilot studies. The median Scottish Intercollegiate Guidelines Network level of evidence grade was 3 and the median Oxford Center for Evidence-based Medicine level of evidence grade was 4. Fewer than 50% of the articles in the current study applied Standardization of Uveitis Nomenclature (SUN) criteria in regard to reporting the anatomic location of uveitis, fewer than 25% of studies applied SUN criteria in regard to the reporting of anterior chamber cells before and after PPV, fewer than 10% of studies applied SUN criteria to the grading of anterior chamber flare before and after PPV, and fewer than 10% of studies applied standardized criteria to the grading of vitreous haze after PPV. Overall, 627 patients and 708 total eyes undergoing PPV for uveitis were included. The average reported age of all patients was 43.4 years. The median duration of uveitis prior to PPV reported in the studies was 36.1 months (range 4-198 months). The median follow-up after PPV reported in the studies was 18.9 months (range 2-114 months). Vision was reported for 519 eyes and was improved in 356 eyes (69%), unchanged in 95 eyes (18%), and worse in 68 eyes (13%) following PPV. Preoperatively, 157 of 300 (52%) eyes in these studies had documented cystoid macular edema compared to 112 of 300 (37%) postoperatively. Median use of oral corticosteroids improved from 48% preoperatively to 12% postoperatively among the reporting studies. Median use of other immunosuppressive medications decreased from 56% preoperatively to 36% postoperatively among the reporting studies.
CONCLUSIONS
Although nearly all studies continue to report favorable outcomes of PPV in the management of uveitis, the quality of data remains limited by a lack of application of standardized reporting outcomes, limitations in study design, and a paucity of prospective data.
Topics: Drug Utilization; Glucocorticoids; Humans; Immunosuppressive Agents; Uveitis; Vitrectomy
PubMed: 29601822
DOI: 10.1016/j.ajo.2018.03.031 -
Seminars in Arthritis and Rheumatism Dec 2020Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management.
Efficacy and safety of immunomodulatory drugs in patients with non-infectious intermediate and posterior uveitis, panuveitis and macular edema: A systematic literature review.
BACKGROUND
Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management.
OBJECTIVES
To evaluate the published evidence regarding the use of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME).
METHODS
We performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale.
RESULTS
Nineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis.
CONCLUSION
Several IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes.
Topics: Adult; Humans; Macular Edema; Panuveitis; Pharmaceutical Preparations; Treatment Outcome; Uveitis; Uveitis, Posterior
PubMed: 33065425
DOI: 10.1016/j.semarthrit.2020.08.010 -
Journal of Digestive Diseases Feb 2021Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent oral aphthous ulcers, intestinal lesions, genital ulcers, uveitis, and skin lesions.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent oral aphthous ulcers, intestinal lesions, genital ulcers, uveitis, and skin lesions. Evidence regarding mucosal healing for the prognosis of intestinal BD is scarce. The aim of this systematic review and meta-analysis was to determine the association between mucosal healing and long-term outcomes of patients with intestinal BD.
METHODS
Relevant studies were identified in a comprehensive search of PubMed, Cochrane Library, and EMBASE databases. Studies reporting long-term outcomes of mucosal healing in patients with intestinal BD were included. Pooled risk ratio (RR) and 95% confidence interval (CI) for disease recurrence and surgery were calculated using the Mantel-Haenszel random-effects models. Heterogeneity among the eligible studies was evaluated using the Q test and I statistics.
RESULTS
Of the 4785 studies initially identified, 8 were finally included. The pooled RR for the association between mucosal healing and disease recurrence was 0.41 (95% CI 0.30-0.57, P < 0.001). For the association between mucosal healing and the risk of surgery, the pooled RR was 0.33 (95% CI 0.17-0.63, P < 0.001). Confounding factors were adjusted in one study, whereas other studies only reported a crude association between mucosal healing and long-term outcomes without adjustment.
CONCLUSIONS
Mucosal healing is associated with a decreased risk of recurrence and surgery in intestinal BD. However, more studies are required given a small number of currently eligible studies and insufficient adjustment for confounding factors.
Topics: Behcet Syndrome; Humans; Intestinal Diseases; Intestines; Prognosis; Stomatitis, Aphthous
PubMed: 33314672
DOI: 10.1111/1751-2980.12965 -
The British Journal of Ophthalmology Aug 2020Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD...
BACKGROUND
Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD manifestations.
OBJECTIVE
To review the evidence base for biologics in the treatment of ocular BD.
METHODS
Systematic literature search was made using exploded key words-Behçet's, ocular, biologics in MEDLINE, Cochrane library, Database of Abstracts Reviews and Effects, Clinical Trials.gov, Science Direct and Google Scholar. There was no limitation on region, language or date (Search updated 16th October 2018). Literature retrieval was restricted to randomised controlled trials (RCTs) of biologics.
RESULTS
Of 237 papers retrieved, eight met the inclusion criteria. RCTs on interferon alpha 2a (INF-α 2a), adalimumab, secukinumab, gevokizumab, rituximab and daclizumab were retrieved (two for adalimumab and gevokizumab). The outcome measures were not met for secukinumab, daclizumab and gevokizumab. Rituximab and INF-α 2a showed promising preliminary results but sufficiently powered RCTs are needed to provide adequate evidence of efficacy. The RCTs on adalimumab did not evaluate efficacy for BD uveitis specifically, hence are of limited value for this review.
CONCLUSION
Some biologics show promise in treating BD uveitis, but more RCTs are needed for firm conclusions about efficacy. A phase IV study or, registry of adalimumab could provide data on its efficacy in BD uveitis compared to other forms.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Behcet Syndrome; Biological Factors; Biological Therapy; Daclizumab; Humans; Interferon-alpha; Rituximab; Uveitis
PubMed: 31676596
DOI: 10.1136/bjophthalmol-2019-314154 -
Autoimmunity Reviews Aug 2018Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the... (Review)
Review
INTRODUCTION
Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the HLA B51 antigen. In rare and severe early onset cases, dominant Mendelian transmission has been linked to mutations in the TNFAIP3 gene encoding A20. Herein, we propose a systematic review of the literature about the haploinsufficiency A20 (HA20) published cases.
SYSTEMATIC REVIEW
Our review of the 45 cases of HA20 from literature highlights the similarities and the differences between this genetic auto-inflammatory disease and classical BD. HA20 looks like BD if we consider recurrent oral (87%) and genital (67%) ulcers, arthralgia or arthritis (42%), skin involvement (53%) such as erythema nodosum or abdominal symptoms (60%) such as abdominal pain, digestive ulcers or diarrhea. However, HA20 differs from classical BD because its geographical distribution is ubiquitous, sex ratio is inversed (one man for two women), first symptoms occur in early childhood (median age = 5.5 years; interquartile range: 1-10) instead of adulthood, recurrent fever is common (62%) unlike classical BD, HLA B51 antigen is uncommon and abdominal symptoms are over-represented compared to classical BD. In addition, response to colchicine in HA20 is inconstant (24%) unlike classical BD.
DISCUSSION/CONCLUSION
High fever flares and digestive involvement starting in early childhood seem to be hallmarks of HA20 clinical features. Response to colchicine is unpredictable and biotherapies like anti-TNFα and anti IL1 appear to be treatments of choice, like for other auto-inflammatory diseases. Prospective description of larger cohort of HA20 cases is needed to understand better when this disease must be looked for and how to treat these patients.
Topics: Behcet Syndrome; Genes, Dominant; Genetic Predisposition to Disease; Haploinsufficiency; Humans; Tumor Necrosis Factor alpha-Induced Protein 3
PubMed: 29890348
DOI: 10.1016/j.autrev.2018.02.012 -
Medicina Clinica Sep 2020To generate recommendations on the use of immunomodulators in patients with non-infectious, non-neoplastic intermediate uveitis (IU), posterior uveitis (PU) and...
OBJECTIVE
To generate recommendations on the use of immunomodulators in patients with non-infectious, non-neoplastic intermediate uveitis (IU), posterior uveitis (PU) and panuveitis (PanU) based on best evidence and experience.
METHODS
A multidisciplinary panel of 5 experts was established, who defined the scope, users, and sections of the document. A systematic literature review (SLR) was performed to assess the efficacy and safety of immunomodulatory drugs in patients with non-infectious, non-neoplastic, non-anterior uveitis. The results of the SLR were presented and discussed during an expert meeting in which 34 recommendations were generated. The level of agreement with the recommendations was also tested in 25 additional experts following a Delphi process. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of the experts voted ≥7. The level of evidence and grade or recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence.
RESULTS
The SLR included 33 articles. The 34 recommendations were accepted after 2 Delphi rounds (3 of them were modified after the first round). They include specific recommendations on patients with non-infectious, non-neoplastic, PU and PanU, as well as different treatment guidelines.
CONCLUSIONS
In patients with non-infectious, non-neoplastic, non-anterior uveitis these recommendations might help treatment decision making, due to the lack of robust evidence or other globally accepted algorithms.
Topics: Evidence-Based Medicine; Humans; Immunosuppressive Agents; Panuveitis; Uveitis; Uveitis, Anterior
PubMed: 32199631
DOI: 10.1016/j.medcli.2019.10.023 -
The Cochrane Database of Systematic... Sep 2014Behçet's disease is a chronic inflammatory vasculitis that can affect multiple systems. Mucocutaneous involvement is common, as is the involvement of many other systems... (Review)
Review
BACKGROUND
Behçet's disease is a chronic inflammatory vasculitis that can affect multiple systems. Mucocutaneous involvement is common, as is the involvement of many other systems such as the central nervous system and skin. Behç̧et's disease can cause significant morbidity, such as loss of sight, and can be life threatening. The frequency of oral ulceration in Behçet's disease is thought to be 97% to 100%. The presence of mouth ulcers can cause difficulties in eating, drinking, and speaking leading to a reduction in quality of life. There is no cure for Behçet's disease and therefore treatment of the oral ulcers that are associated with Behçet's disease is palliative.
OBJECTIVES
To determine the clinical effectiveness and safety of interventions on the pain, episode duration, and episode frequency of oral ulcers and on quality of life for patients with recurrent aphthous stomatitis (RAS)-type ulceration associated with Behçet's disease.
SEARCH METHODS
We undertook electronic searches of the Cochrane Oral Health Group Trials Register (to 4 October 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE via Ovid (1946 to 4 October 2013); EMBASE via Ovid (1980 to 4 October 2013); CINAHL via EBSCO (1980 to 4 October 2013); and AMED via Ovid (1985 to 4 October 2013). We searched the US National Institutes of Health trials register (http://clinicaltrials.gov) and the World Health Organization (WHO) Clinical Trials Registry Platform for ongoing trials. There were no restrictions on language or date of publication in the searches of the electronic databases. We contacted authors when necessary to obtain additional information.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that looked at pre-specified oral outcome measures to assess the efficacy of interventions for mouth ulcers in Behçet's disease. The oral outcome measures included pain, episode duration, episode frequency, safety, and quality of life. Trials were not restricted by outcomes alone.
DATA COLLECTION AND ANALYSIS
All studies meeting the inclusion criteria underwent data extraction and an assessment of risk of bias, independently by two review authors and using a pre-standardised data extraction form. We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
A total of 15 trials (n = 888 randomised participants) were included, 13 were placebo controlled and three were head to head (two trials had more than two treatment arms). Eleven of the trials were conducted in Turkey, two in Japan, one in Iran and one in the UK. Most trials used the International Study Group criteria for Behçet's disease. Eleven different interventions were assessed. The interventions were grouped into two categories, topical and systemic. Only one study was assessed as being at low risk of bias. It was not possible to carry out a meta-analysis. The quality of the evidence ranged from moderate to very low and there was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration, or episode frequency associated with oral ulcers, or safety of the interventions.
AUTHORS' CONCLUSIONS
Due to the heterogeneity of trials including trial design, choice of intervention, choice and timing of outcome measures, it was not possible to carry out a meta-analysis. Several interventions show promise and future trials should be planned and reported according to the CONSORT guidelines. Whilst the primary aim of many trials for Behç̧et's disease is not necessarily reduction of oral ulceration, reporting of oral ulcers in these studies should be standardised and pre-specified in the methodology. The use of a core outcome set for oral ulcer trials would be beneficial.
Topics: Acyclovir; Adrenal Cortex Hormones; Alanine; Behcet Syndrome; Colchicine; Cyclosporine; Etanercept; Humans; Immunoglobulin G; Interferon-alpha; Oral Ulcer; Quinolones; Randomized Controlled Trials as Topic; Receptors, Tumor Necrosis Factor; Stomatitis, Aphthous; Sucralfate; Thalidomide
PubMed: 25254615
DOI: 10.1002/14651858.CD011018.pub2 -
Seminars in Arthritis and Rheumatism Apr 2016A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the... (Review)
Review
OBJECTIVE
A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA).
METHODS
Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs.
RESULTS
Some variables, including the patients' preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or UTK choice is guided by skin or articular disease severity, enthesitis, and dactylitis, whereas ETN should be preferred if metabolic syndrome or high CV risk complicate PsA.
CONCLUSION
Taking in account of multiple choice driving variables, first-line biologic therapy may be optimized in patients with RA, SpA, and PsA.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Biological Products; Cost-Benefit Analysis; Humans; Precision Medicine; Spondylarthritis
PubMed: 26607440
DOI: 10.1016/j.semarthrit.2015.10.001 -
Ocular Immunology and Inflammation Jan 2024To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU).
METHODS
A systematic review and meta-analysis of observational studies was performed. Pooled results are presented as mean difference or standardized mean difference (std diff) and 95% confidence intervals (CI). Visual acuity (VA), intraocular inflammation grade, central macular thickness, corticosteroid (CS) sparing effect and adverse events were evaluated.
RESULTS
Ten studies were included finally for quantitative and qualitative synthesis. ADA therapy resulted in 0.124 (95%CI: 0.084, 0.165) logMAR improvement in VA. In addition, ADA therapy resulted in decreased grade of intraocular inflammation [std diff, -1.187 (95%CI: -1.508, -0.866)] and macular thickness [std diff, -0.564 (95%CI: -0.843, -0.286)] and caused a decrease in CS dosage [std diff, -1.809 (95%CI: -2.420, -1.198)]. The pooled rate of overall adverse events for ADA in 301 patients was 8.5% (95%CI: 0.039, 0.177).
CONCLUSION
ADA is an efficient therapy that improves VA and controls intraocular inflammation, macular edema and retinal vasculitis. As the disease exposure time increased, improvement in VA was less. The safety and CS-sparing effect of ADA were demonstrated with few adverse effects. The results provided evidence that ADA can be used safely and efficiently as the first-line drug in patients with BU.
Topics: Humans; Adalimumab; Uveitis; Behcet Syndrome; Inflammation; Retinal Vasculitis
PubMed: 36625549
DOI: 10.1080/09273948.2022.2157288