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Clinical Gastroenterology and... Aug 2023Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]).
METHODS
We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model.
RESULTS
Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I = 0%; P = .12), PB (OR, 1.10; I = 0%; P = .17), or CM (OR, 1.03; I = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I = 19%; P = .17), PB (OR, 1.05; I = 0%; P = .20), or CM (OR, 1.07; I = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I = 0%; P = .62) or CM (OR, 1.03; I = 0%; P = .81).
CONCLUSIONS
Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.
Topics: Pregnancy; Female; Male; Humans; Infant, Newborn; Methotrexate; Premature Birth; Semen; Inflammatory Bowel Diseases; Abortion, Spontaneous; Fertility
PubMed: 35870769
DOI: 10.1016/j.cgh.2022.07.008 -
Expert Opinion on Drug Metabolism &... Apr 2024High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to...
INTRODUCTION
High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment.
AREAS COVERED
A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified.
EXPERT OPINION
This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.
Topics: Humans; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Interactions; Hematologic Neoplasms; Methotrexate; Polymorphism, Genetic; Precision Medicine; Risk Factors
PubMed: 38501267
DOI: 10.1080/17425255.2024.2332366 -
Journal of Clinical Rheumatology :... Jan 2024Sarcopenia is underrecognized in patients with rheumatoid arthritis (RA). Risk factors of sarcopenia and its impact on outcomes in RA patients are relatively unknown. We... (Meta-Analysis)
Meta-Analysis
Sarcopenia is underrecognized in patients with rheumatoid arthritis (RA). Risk factors of sarcopenia and its impact on outcomes in RA patients are relatively unknown. We conducted a systematic review to identify factors and outcomes associated with sarcopenia in RA. We conducted this review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. We searched PubMed, Embase, CINAHL, and Web of Science databases by combining the following search concepts: (1) RA and (2) sarcopenia. Articles were included if they included RA patients, assessed for sarcopenia using a consensus working group definition, and assessed for clinical outcomes. Meta-analysis was performed using studies that shared the same sarcopenia definition and consistency in reporting patient or disease variables. Our search identified 3602 articles. After removal of duplicates, title and abstract screen, and full-text review, 16 articles were included for final analysis. All studies had observational study designs. The pooled prevalence of sarcopenia ranged from 24% to 30%, depending on the criteria for sarcopenia used. Factors associated with sarcopenia included higher 28-joint Disease Activity Scale scores (+0.39; 95% confidence interval, +0.02 to +0.77) and baseline methotrexate use (odds ratio, 0.70; 95% confidence interval, 0.51-0.97). Baseline glucocorticoid use had a positive correlation with sarcopenia in multiple studies. Several studies found lower bone mineral density and higher incidence of falls and fractures in patients with sarcopenia. Sarcopenia is prevalent in RA, and it may be associated with higher RA disease activity, lower bone mineral density, and increased falls and fractures. Therefore, early screening of sarcopenia in RA patients is important to incorporate into clinical rheumatology practice.
Topics: Humans; Sarcopenia; Arthritis, Rheumatoid; Risk Factors; Methotrexate; Observational Studies as Topic
PubMed: 37092889
DOI: 10.1097/RHU.0000000000001980 -
Advances in Rheumatology (London,... Jul 2023Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi... (Meta-Analysis)
Meta-Analysis
Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.
BACKGROUND
Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents.
METHODS
We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response.
RESULTS
The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab.
CONCLUSION
We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.
Topics: Humans; Abatacept; Rituximab; Methotrexate; Tumor Necrosis Factor Inhibitors; Antirheumatic Agents; Network Meta-Analysis; Arthritis, Rheumatoid
PubMed: 37415193
DOI: 10.1186/s42358-023-00298-z -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
RMD Open Jan 2024An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients.
OBJECTIVES
To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA.
METHODS
A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response.
RESULTS
The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the 'without MTX' subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70.
CONCLUSIONS
Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.
Topics: Adult; Humans; United States; Methotrexate; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Antibodies, Monoclonal; Network Meta-Analysis; Bayes Theorem; Tumor Necrosis Factor Inhibitors; Biological Products
PubMed: 38296801
DOI: 10.1136/rmdopen-2023-003423 -
BJOG : An International Journal of... Jan 2024Tubal ectopic pregnancy (TEP) is a common gynaecological emergency. Several medical and surgical treatment options exist, but it is not clear which is the safest and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tubal ectopic pregnancy (TEP) is a common gynaecological emergency. Several medical and surgical treatment options exist, but it is not clear which is the safest and most effective treatment.
OBJECTIVES
To compare the effectiveness of expectant, medical and surgical treatment options for TEP using a systematic review and network meta-analysis.
SEARCH STRATEGY
MEDLINE, EMBASE, and CENTRAL from inception till September 2022.
SELECTION CRITERIA
Randomised trials that evaluated any treatment option for woman with a TEP.
DATA COLLECTION AND ANALYSIS
We performed pairwise and network meta-analyses using a random effect model. We assessed the studies' risk of bias, heterogeneity and network inconsistency. We reported primarily on TEP resolution and treatment failure using relative risk (RR) and 95% confidence-intervals (CI).
MAIN RESULTS
We included 31 randomised trials evaluating ten treatments (n = 2938 women). Direct meta-analysis showed no significant benefit for using methotrexate compared to expectant management for TEP resolution. Network meta-analysis showed similar effect-size for most conservative treatment options compared to expectant management for TEP resolution (glucose intra-sac instillation vs. expectant RR 0.84, 95% CI 0.63-1.12; methotrexate intra-sac instillation vs. expectant RR 0.91, 95% CI 0.75-1.10; multi-dose methotrexate vs. expectant RR 1.00, 95% CI 0.88-1.15; prostaglandin intra-sac instillation vs. expectant RR 0.75, 95% CI 0.53-1.07; salpingotomy vs. expectant RR 0.99, 95% CI 0.84-1.16; single dose methotrexate vs. expectant RR 0.97, 95% CI 0.85-1.10; single dose methotrexate + mifepristone vs. expectant RR 1.09, 95% CI 0.89-1.33). All treatment options showed a higher risk of failure compared to salpingectomy.
CONCLUSIONS
There is insufficient evidence to support the use of any medical treatment option for TEP over expectant management.
Topics: Pregnancy; Female; Humans; Methotrexate; Network Meta-Analysis; Mifepristone; Prostaglandins; Pregnancy, Ectopic
PubMed: 37443463
DOI: 10.1111/1471-0528.17594 -
BMC Ophthalmology Nov 2023Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton's tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain.
METHODS
A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies.
RESULTS
The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%).
CONCLUSION
The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects.
TRIAL REGISTRATION
CRD42023400305.
Topics: Humans; Methotrexate; Retinal Neoplasms; Prospective Studies; Vitreous Body; Central Nervous System Neoplasms; Lymphoma
PubMed: 37993841
DOI: 10.1186/s12886-023-03226-3 -
Journal of Clinical Rheumatology :... Oct 2023To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK).
OBJECTIVE
To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK).
METHODS
A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members.
RESULTS
Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible.
CONCLUSION
The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.
Topics: Humans; United States; Takayasu Arteritis; Tumor Necrosis Factor Inhibitors; Rheumatology; Immunosuppressive Agents; Methotrexate
PubMed: 37553869
DOI: 10.1097/RHU.0000000000002004 -
World Journal of Urology Aug 2023The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank... (Meta-Analysis)
Meta-Analysis
Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.
PURPOSE
The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them.
METHODS
We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment.
RESULTS
Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options.
CONCLUSION
No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.
Topics: Humans; Cisplatin; Neoadjuvant Therapy; Methotrexate; Bayes Theorem; Network Meta-Analysis; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Urinary Bladder Neoplasms; Doxorubicin; Vinblastine; Cystectomy
PubMed: 37347252
DOI: 10.1007/s00345-023-04478-w