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Frontiers in Pharmacology 2022: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative...
: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. : Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). : A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. : Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1-13 weeks or 3 months administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.
PubMed: 36339579
DOI: 10.3389/fphar.2022.1036593 -
The Cochrane Database of Systematic... Apr 2016Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis.
OBJECTIVES
The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens.
SEARCH METHODS
A computer-assisted literature search for relevant studies (inception to July 9, 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies.
SELECTION CRITERIA
Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion.
DATA COLLECTION AND ANALYSIS
The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis.
MAIN RESULTS
Fifty-three studies (8548 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-one per cent of 5-ASA patients failed to enter clinical remission compared to 83% of placebo patients (RR 0.86, 95% CI 0.82 to 0.89). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-five per cent of once daily patients failed to enter clinical remission compared to 48% of conventionally dosed patients (RR 0.94, 95% CI 0.83 to 1.07). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent of patients in the 5-ASA group failed to enter remission compared to 52% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02). A pooled analysis of 3 studies (n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63).
AUTHORS' CONCLUSIONS
5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Induction Chemotherapy; Mesalamine; Randomized Controlled Trials as Topic; Sulfasalazine; Treatment Failure
PubMed: 27101467
DOI: 10.1002/14651858.CD000543.pub4 -
The Cochrane Database of Systematic... Oct 2015The therapeutic role of 6-mercaptopurine (6-MP) and azathioprine (AZA) remains controversial due to their perceived relatively slow-acting effect and adverse effects. An... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic role of 6-mercaptopurine (6-MP) and azathioprine (AZA) remains controversial due to their perceived relatively slow-acting effect and adverse effects. An updated meta-analysis was performed to evaluate the efficacy of these agents for the maintenance of remission in quiescent Crohn's disease.
OBJECTIVES
To assess the efficacy of AZA and 6-MP for maintenance of remission in quiescent Crohn's disease.
SEARCH METHODS
We searched MEDLINE, EMBASE, and the Cochrane Library from inception to June 30, 2015.
SELECTION CRITERIA
Randomized controlled trials of oral azathioprine or 6-mercaptopurine compared to placebo or active therapy involving adult patients (> 18 years) with quiescent Crohn's disease were considered for inclusion. Patients with surgically-induced remission were excluded.
DATA COLLECTION AND ANALYSIS
At least two authors independently extracted data and assessed study quality using the Cochrane risk of bias tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (CI). The primary outcomes was maintenance of remission. Secondary outcomes included steroid sparing, adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria.
MAIN RESULTS
Eleven studies (881 participants) were included. Comparisons included AZA versus placebo (7 studies, 532 participants), AZA or 6-MP versus mesalazine or sulfasalazine (2 studies, 166 participants), AZA versus budesonide (1 study, 77 participants), AZA and infliximab versus infliximab (1 study, 36 patients), 6-MP versus methotrexate (1 study, 31 patients), and early AZA versus conventional management (1 study, 147 participants). Two studies were rated as low risk of bias. Three studies were rated as high risk of bias for being non-blinded. Six studies were rated as unclear risk of bias. A pooled analysis of six studies (489 participants) showed that AZA (1.0 to 2.5 mg/kg/day) was significantly superior to placebo for maintenance of remission over a 6 to 18 month period. Seventy-three per cent of patients in the AZA group maintained remission compared to 62% of placebo patients (RR 1.19, 95% CI 1.05 to 1.34). The number needed to treat for an additional beneficial outcome was nine. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (327 events) and unclear risk of bias. A pooled analysis of two studies (166 participants) showed no statistically significant difference in the proportion of patients who maintained remission between AZA (1.0 to 2.5 mg/kg/day) or 6-MP (1.0 mg/day) and mesalazine (3 g/day) sulphasalazine (0.5 g/15 kg) therapy. Sixty-nine per cent of patients in the AZA/6-MP group maintained remission compared to 67% of mesalazine/sulphasalazine patients (RR 1.09, 95% CI 0.88 to 1.34). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (113 events) and high or unclear risk of bias. One small study found AZA (2.0 to 2.5 mg/kg/day) to be superior to budesonide (6 to 9 mg/day) for maintenance of remission at one year. Seventy-six per cent (29/38) of AZA patients maintained remission compared to 46% (18/39) of budesonide patients (RR 1.65, 95% CI 1.13 to 2.42). GRADE indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (47 events) and high risk of bias. One small study found no difference in maintenance of remission rates at one year between combination therapy with AZA (2.5 mg/kg) and infliximab (5 mg/kg every 8 weeks) compared to infliximab monotherapy. Eighty-one per cent (13/16) of patients in the combination therapy group maintained remission compared to 80% (16/20) of patients in the infliximab group (RR 1.02, 95% CI 0.74 to 1.40). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (29 events) and unclear risk of bias. One small study found no difference in maintenance of remission rates at one year between 6-MP (1 mg/day) and methotrexate (10 mg/week). Fifty per cent (8/16) of 6-MP patients maintained remission at one year compared to 53% (8/15) of methotrexate patients (RR 0.94, 95% CI 0.47 to 1.85). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (16 events) and high risk of bias. One study (147 participants) failed to show any significant benefit for early azathioprine treatment over a conventional management strategy. In the early azathioprine treatment group 67% (11-85%) of the trimesters were spent in remission compared to 56% (29-73%) in the conventional management group. AZA when compared to placebo had significantly increased risk of adverse events (RR 1.29, 95% CI 1.02 to 1.64), withdrawal due to adverse events (3.12, 95% CI 1.59 to 6.09) and serious adverse events (RR 2.45, 95% CI 1.22 to 4.90). AZA/6-MP also demonstrated a significantly higher risk of serious adverse events when compared to mesalazine or sulphasalazine (RR 9.37, 95% CI 1.84 to 47.7). AZA/6-MP did not differ significantly from other active therapies with respect to adverse event data. Common adverse events included pancreatitis, leukopenia, nausea, allergic reaction and infection.
AUTHORS' CONCLUSIONS
Low quality evidence suggests that AZA is more effective than placebo for maintenance of remission in Crohn's disease. Although AZA may be effective for maintenance of remission its use is limited by adverse effects. Low quality evidence suggests that AZA may be superior to budesonide for maintenance of remission but because of small study size and high risk of bias, this result should be interpreted with caution. No conclusions can be drawn from the other active comparator studies because of low and very low quality evidence. Adequately powered trials are needed to determine the comparative efficacy and safety of AZA and 6-MP compared to other active maintenance therapies. Further research is needed to assess the efficacy and safety of the use of AZA with infliximab and other biologics and to determine the optimal management strategy for patients quiescent Crohn's disease.
Topics: Azathioprine; Crohn Disease; Humans; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Prodrugs; Randomized Controlled Trials as Topic
PubMed: 26517527
DOI: 10.1002/14651858.CD000067.pub3 -
Alimentary Pharmacology & Therapeutics May 2017The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research.
AIM
To investigate this association through an updated meta-analysis of observational studies.
METHODS
PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates were calculated using random-effect models. Detailed subgroup analyses were performed. The GRADE approach was used to assess the quality of evidence.
RESULTS
Thirty-one independent observational studies including 2137 cases of colorectal neoplasia (of which 76% were cancers) were incorporated. Between-study heterogeneity was moderate, while strong suspicion of small-study effects was raised. The overall analysis revealed a protective association between 5-aminosalicylates' use and colorectal neoplasia (RR = 0.57, 95% CI: 0.45-0.71). When the analysis was stratified according to study design and setting, the association was significant in cohort (RR = 0.65, 95% CI: 0.43-0.99; n = 10) and case-control studies (RR = 0.53, 95% CI: 0.40-0.70; n = 21), population-based (RR = 0.70, 95% CI: 0.52-0.94; n = 12) and hospital-based studies (RR = 0.46, 95% CI: 0.34-0.61; n = 19). Exposure to 5-aminosalicylates was protective against cancer (RR = 0.58, 95% CI: 0.45-0.74) and dysplasia (RR = 0.54, 95% CI: 0.35-0.84). The reduction in colorectal neoplasia risk was strong in ulcerative colitis (RR = 0.50, 95% CI: 0.38-0.64), but nonsignificant in Crohn's disease (RR = 0.76, 95% CI: 0.43-1.33). Mesalazine (mesalamine) use was protective (RR = 0.70, 95% CI: 0.51-0.94) with evidence of a dose-effect. The effect of sulfasalazine was marginally nonsignificant (RR = 0.72, 95% CI: 0.51-1.01).
CONCLUSIONS
Our findings support a potential chemopreventive role of 5-aminosalicylates in IBD. Further, high-quality prospective research is warranted.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colorectal Neoplasms; Crohn Disease; Humans; Mesalamine; Risk
PubMed: 28261835
DOI: 10.1111/apt.14023 -
American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
BMC Complementary and Alternative... Jul 2016Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis... (Meta-Analysis)
Meta-Analysis Review
Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis.
BACKGROUND
Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis (RA), but its clinical efficacy and safety remain largely undefined in comparison with conventional synthetic disease modifying anti-rheumatic drugs (DMARDs).
METHODS
PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang Databases. Endpoints were ACR 20, 50, and 70, and the number of withdrawals due to adverse events. Initially, traditional pairwise meta-analysis was performed by using a random-effects model. Then, we performed network meta-analysis to compare different therapies by using frequentist approach.
RESULTS
A total of 22 trials (5255 participants) were identified. By direct comparison, TwHF was superior to sulphasalazine according to ACR 20, 50 and 70. TwHF was superior to placebo according to ACR 20 and 50. By indirect comparisons, TwHF was superior to methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline and placebo according to ACR 20. Ranking by the Surface under the Cumulative Ranking curve (SUCRA) values showed that TwHF had the greatest probability for being the best treatment option according to ACR 20 (92.0 %) and ACR 50 (81.3 %), and the highest probability to be in the second (57.8 %) ranking position after leflunomide (69.6 %) according to ACR 70. By both direct and indirect comparisons, TwHF caused no more significant withdrawals than the placebo. The SUCRA values showed that TwHF had the highest probability to rank sixth (26.7 %) after the placebo (45.6 %) in causing withdrawals.
CONCLUSIONS
Our data suggest that TwHF is effective and safe in the treatment of RA and has better clinical efficacy in terms of ACR 20 and 50 than existing conventional synthetic DMARDs. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Plant Extracts; Tripterygium
PubMed: 27411429
DOI: 10.1186/s12906-016-1194-x -
Journal of Clinical Gastroenterology Mar 2017To evaluate the role of folic acid supplementation in colorectal cancer (CRC) chemoprevention in patients with inflammatory bowel disease (IBD). (Meta-Analysis)
Meta-Analysis Review
GOALS
To evaluate the role of folic acid supplementation in colorectal cancer (CRC) chemoprevention in patients with inflammatory bowel disease (IBD).
BACKGROUND
CRC is a serious complication of IBD. Folic acid supplementation has been shown to be chemopreventative in sporadic CRC. Patients with IBD are at risk of folate deficiency though intestinal malabsorption and also competitive inhibition by concurrent sulfasalazine use. To date, there have been several studies reporting on folic acid supplementation in patients with IBD and CRC.
STUDY
We searched electronic databases for studies reporting folic acid use and CRC incidence in patients with IBD. We produced a pooled hazard ratio with 95% confidence intervals using a random-effects model. Preplanned subgroup analyses were performed to explore for any potential sources of heterogeneity.
RESULTS
Ten studies reporting on 4517 patients were included. We found an overall protective effect for folic acid supplementation on the development of CRC, pooled hazard ratio=0.58 (95% confidence interval, 0.37-0.80). There was low to moderate heterogeneity among studies, I=29.7%. Subgroup analyses suggested that folic acid use was protective in hospital-based studies, studies from North America and those that were performed before folate fortification of foods in 1998.
CONCLUSIONS
CRC remains an important complication of IBD. Chemoprevention is an attractive strategy and folic acid as a cheap, safe, and well-tolerated supplement may have a role. Focused prospective studies are required to precisely define any potential effect.
Topics: Colorectal Neoplasms; Dietary Supplements; Folic Acid; Humans; Inflammatory Bowel Diseases; Risk Factors
PubMed: 26905603
DOI: 10.1097/MCG.0000000000000498 -
Rheumatology (Oxford, England) Sep 2021Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify...
OBJECTIVE
Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify studies evaluating the different treatment modalities used in CPAN.
METHODS
This systematic review was conducted according to PRISMA guidelines, registered in PROSPERO: CRD42020222195. PubMed/Medline databases were searched from inception to December of 2020 using the terms: (Polyarteritis nodosa[Title/Abstract]) AND ((therapy[Title/Abstract]) OR (management[Title/Abstract]) OR (treatment[Title/Abstract]))' and 'Cutaneous arteritis [Title/Abstract]'. Articles evaluating pertaining to the management of CPAN in adults were eligible for inclusion.
RESULTS
A total of seven eligible case series with 325 unique patients were included. No study included a control population. In general, systemic corticosteroids were widely used as induction treatment. Immunosuppressive agents combined with corticosteroids were AZA, hydroxychloroquine, sulfasalazine, sulphapyridine, CYC, MTX, mycophenolate, tacrolimus, rituxima and thalidomide. Other agents utilized in the studies were dapsone, colchicine, non-steroid anti-inflammatory drugs, salicylates, warfarin and clopidogrel. In some studies, the presence of ulcerations was associated with an increased risk of relapse.
CONCLUSION
The evidence available regarding the management of patients with CPAN is limited at best. Further studies are needed in order to evaluate the effect of treatment on disease remission, relapses and mortality.
Topics: Drug Therapy, Combination; Humans; Polyarteritis Nodosa
PubMed: 33944902
DOI: 10.1093/rheumatology/keab402 -
The Cochrane Database of Systematic... Aug 2016Methotrexate is considered the preferred disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis, but controversy exists on the... (Meta-Analysis)
Meta-Analysis Review
Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis.
BACKGROUND
Methotrexate is considered the preferred disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis, but controversy exists on the additional benefits and harms of combining methotrexate with other DMARDs.
OBJECTIVES
To compare methotrexate and methotrexate-based DMARD combinations for rheumatoid arthritis in patients naïve to or with an inadequate response (IR) to methotrexate.
METHODS
We systematically identified all randomised controlled trials with methotrexate monotherapy or in combination with any currently used conventional synthetic DMARD , biologic DMARDs, or tofacitinib. Three major outcomes (ACR50 response, radiographic progression and withdrawals due to adverse events) and multiple minor outcomes were evaluated. Treatment effects were summarized using Bayesian random-effects network meta-analyses, separately for methotrexate-naïve and methotrexate-IR trials. Heterogeneity was explored through meta-regression and subgroup analyses. The risk of bias of each trial was assessed using the Cochrane risk of bias tool, and trials at high risk of bias were excluded from the main analysis. The quality of evidence was evaluated using the GRADE approach. A comparison between two treatments was considered statistically significant if its credible interval excluded the null effect, indicating >97.5% probability that one treatment was superior.
MAIN RESULTS
158 trials with over 37,000 patients were included. Methotrexate-naïve: Several treatment combinations with methotrexate were statistically superior to oral methotrexate for ACR50 response: methotrexate + sulfasalazine + hydroxychloroquine ("triple therapy"), methotrexate + several biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated probability of ACR50 response was similar between these treatments (range 56-67%, moderate to high quality evidence), compared with 41% for methotrexate. Methotrexate combined with adalimumab, etanercept, certolizumab, or infliximab was statistically superior to oral methotrexate for inhibiting radiographic progression (moderate to high quality evidence) but the estimated mean change over one year with all treatments was less than the minimal clinically important difference of five units on the Sharp-van der Heijde scale. Methotrexate + azathioprine had statistically more withdrawals due to adverse events than oral methotrexate, and triple therapy had statistically fewer withdrawals due to adverse events than methotrexate + infliximab (rate ratio 0.26, 95% credible interval: 0.06 to 0.91). Methotrexate-inadequate response: In patients with an inadequate response to methotrexate, several treatments were statistically significantly superior to oral methotrexate for ACR50 response: triple therapy (moderate quality evidence), methotrexate + hydroxychloroquine (low quality evidence), methotrexate + leflunomide (moderate quality evidence), methotrexate + intramuscular gold (very low quality evidence), methotrexate + most biologics (moderate to high quality evidence), and methotrexate + tofacitinib (high quality evidence). There was a 61% probability of an ACR50 response with triple therapy, compared to a range of 27% to 64% for the combinations of methotrexate + biologic DMARDs that were statistically significantly superior to oral methotrexate. No treatment was statistically significantly superior to oral methotrexate for inhibiting radiographic progression. Methotrexate + cyclosporine and methotrexate + tocilizumab (8 mg/kg) had a statistically higher rate of withdrawals due to adverse events than oral methotrexate and methotrexate + abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments.
AUTHORS' CONCLUSIONS
We found moderate to high quality evidence that combination therapy with methotrexate + sulfasalazine+ hydroxychloroquine (triple therapy) or methotrexate + most biologic DMARDs or tofacitinib were similarly effective in controlling disease activity and generally well tolerated in methotrexate-naïve patients or after an inadequate response to methotrexate. Methotrexate + some biologic DMARDs were superior to methotrexate in preventing joint damage in methotrexate-naïve patients, but the magnitude of these effects was small over one year.
Topics: Administration, Oral; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Drug Therapy, Combination; Humans; Methotrexate; Randomized Controlled Trials as Topic
PubMed: 27571502
DOI: 10.1002/14651858.CD010227.pub2 -
Oncotarget Jan 2017The chemopreventive effect of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) has been widely studied; however, the results remain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The chemopreventive effect of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) has been widely studied; however, the results remain conflicting. The aim of this study was to systematically review the literature and update evidence concerning effects of 5-ASA on the risk of colorectal cancer (CRC) and dysplasia (Dys) in patients with ulcerative colitis (UC) or Crohn's disease (CD).
RESULTS
5-ASA showed a chemopreventive effect against CRC/Dys in IBD patients (OR = 0.58, 95% CI: 0.45-0.75). However, this effect was significant only in clinical-based studies (OR = 0.51; 95% CI: 0.39-0.65), but not in population-based studies (OR = 0.71; 95% CI: 0.46-1.09). Moreover, this effect was noticeable in patients with UC (OR = 0.46, 95% CI: 0.34-0.61), but not in CD (OR = 0.66, 95% CI: 0.42-1.03), and on the outcome of CRC (OR = 0.54, 95% CI: 0.39-0.74), but not Dys (OR = 0.47; 95% CI: 0.20-1.10). In IBD patients, mesalazine dosage ≥ 1.2 g/day showed greater protective effects against CRC/Dys than dosages < 1.2 g/day. However, Sulphasalazine therapy did not show any noticeable protective function regardless of the dosage administered.
MATERIALS AND METHODS
We performed a systematic review with a meta-analysis of 26 observational studies involving 15,460 subjects to evaluate the risks of developing CRC and Dys in IBD patients receiving 5-ASA treatment. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each evaluation index.
CONCLUSIONS
5-ASA has a chemopreventive effect on CRC (but not Dys) in IBD patients. Moreover, UC patients can benefit more from 5-ASA than CD patients. Mesalazine maintenance dosage ≥ 1.2 g/day is an effective treatment for reducing CRC risk in IBD patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemoprevention; Cohort Studies; Colorectal Neoplasms; Humans; Hyperplasia; Inflammatory Bowel Diseases; Mesalamine; Odds Ratio; Population Surveillance; Publication Bias; Risk Assessment; Risk Factors
PubMed: 27906680
DOI: 10.18632/oncotarget.13715