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The Journal of Dermatological Treatment May 2022Psoriasis and inflammatory bowel diseases share common immunological pathomechanisms and therefore similar treatment options. (Review)
Review
BACKGROUND
Psoriasis and inflammatory bowel diseases share common immunological pathomechanisms and therefore similar treatment options.
OBJECTIVE
To assess already existing therapies and their efficacy versus adverse effects and paradoxical reactions in patients presenting with either disease or both.
DATA SOURCES
A systematic search of the PubMed and Science.gov databases was performed for the period 2018-2020. Only articles in English were selected. Search terms included a combination of keywords: and in combination with each of the following: Other potentially relevant articles were identified by manually checking the references of the included literature.
STUDY SELECTION
Recent reviews and meta-analyses, pooled analyses, cohort studies, observational studies, care reports were all included.
CONCLUSIONS
Psoriasis and IBD can be treated concurrently as they share common inflammatory pathways. TNF-α inhibitors and IL-12/23 have been successful in treating both psoriasis and IBD. IL-17 inhibitors are recognized treatments for psoriasis but have the potential to exacerbate IBD. Newer molecules require further clinical trials and real-life studies in order to confirm their efficacy and safety.
Topics: Etanercept; Humans; Inflammatory Bowel Diseases; Infliximab; Psoriasis; Ustekinumab
PubMed: 33074781
DOI: 10.1080/09546634.2020.1836313 -
Current Medical Research and Opinion Nov 2021Pentasa (prolonged-release mesalazine [5-ASA]) has been available for >30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pentasa (prolonged-release mesalazine [5-ASA]) has been available for >30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic literature review and meta-analysis was undertaken to provide an up-to-date evaluation of oral Pentasa efficacy and safety for induction and maintenance of remission.
METHODS
Literature searches were conducted in PubMed, Embase and Cochrane databases, from inception to 02 December 2020. Unpublished studies were also sourced. Meta-analyses using a random-effects model and Bayesian inference compared Pentasa (tablets, granules, capsules) against placebo and other 5-ASAs.
RESULTS
Twelve studies involving 3674 patients treated with Pentasa were identified. Pentasa 2-4 g/day was superior to placebo at inducing (absolute risk difference [ARD] at 8 weeks 0.14, 95% CI 0.07‒0.21; < .001) and maintaining (ARD 6-12 months 0.18, 95% CI 0.04‒0.33; < .05) remission (clinical/endoscopic). Against other 5-ASAs, Pentasa had similar efficacy for induction (ARD <0.001, 95% CI -0.05‒0.05) and maintenance (ARD 0.01, 95% CI -0.07‒0.08) treatment using randomized controlled trial data. Upon inclusion of real-world study data, Pentasa was significantly better at maintaining remission compared both to Eudragit-S mesalazine and sulfasalazine (ARD 0.04, 95% CI 0.02‒0.06; < .001). Pentasa (1-4 g/day) had similar treatment-related adverse event rates to placebo (ARD 0.02, 95% CI -0.03‒0.06) and Eudragit-L/S mesalazines (2.25-3 vs 2.4-3 g/day, respectively; ARD -0.03, 95% CI -0.12‒0.05), but was better tolerated than sulfasalazine (3 g/day) (ARD 0.07, 95% CI 0.003‒0.14; < .05).
CONCLUSION
This study confirms oral Pentasa is efficacious and well-tolerated in treating active UC and maintaining remission. The availability of multiple forms of Pentasa supports physicians' ability to individualize treatment and optimize dosing to improve outcomes.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Colitis, Ulcerative; Humans; Mesalamine
PubMed: 34404286
DOI: 10.1080/03007995.2021.1968813 -
Inflammatory Bowel Diseases Nov 2015In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only... (Meta-Analysis)
Meta-Analysis Review
Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis.
BACKGROUND
In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined.
METHODS
We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies.
RESULTS
Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting.
CONCLUSIONS
Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colorectal Neoplasms; Humans; Inflammatory Bowel Diseases; Mesalamine; Risk Assessment; Sulfasalazine
PubMed: 26296062
DOI: 10.1097/MIB.0000000000000540 -
Journal of Clinical Pharmacy and... Aug 2000To assess the effectiveness, safety and cost implications of leflunomide treatment for rheumatoid arthritis. (Review)
Review
OBJECTIVE
To assess the effectiveness, safety and cost implications of leflunomide treatment for rheumatoid arthritis.
DESIGN
Systematic review.
SETTING
Four trials retrieved from Medline, Embase, the Cochrane Library, Econlit, HMIC (Dhdata), HMIC (Helmis), HMIC (King's Fund Database) and Best Evidence3.
MAIN OUTCOME MEASURES
Efficacy measures (including tender joint counts, swollen joint counts, assessment of functioning, Health Assessment Questionnaire, Modified Health Assessment Questionnaire, pain (visual analogue scale), Erythrocyte Sedimentation Rate, C-reactive Protein), radiological progression and treatment adverse events.
RESULTS
Leflunomide therapy was demonstrated to be significantly superior to placebo in relation to the efficacy outcome measures and it slowed the radiological progression of patients' disease in three studies. Treatment success and duration of sustained response were also significantly superior than on placebo, as were quality of life measures. Leflunomide treatment was comparable to sulphasalazine and methotrexate with respect to efficacy, radiological progression and quality of life measures. The most common adverse effects leading to withdrawal from leflunomide treatment were gastrointestinal symptoms (diarrhoea and nausea), allergic reactions (rash and pruritus), alopecia, dyspepsia, hypertension and elevated transaminase levels. Weight loss and dizziness have also been reported for leflunomide therapy. Leflunomide is more expensive than most DMARDs, costing about pound400 a year more than sulphasalazine.
CONCLUSION
Despite the small number of published articles relating to leflunomide treatment, the evidence suggests that leflunomide is similar in efficacy to both sulphasalazine and methotrexate, although with a differential pattern of side-effects. There is a need for further research to assess the long-term outcomes of leflunomide treatment.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Cost-Benefit Analysis; Disease Progression; Drug Costs; Humans; Isoxazoles; Leflunomide; Pain; Treatment Outcome
PubMed: 10971781
DOI: 10.1046/j.1365-2710.2000.00296.x -
The Cochrane Database of Systematic... Nov 2014Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and affects mainly the spine, but can also affect other joints. Disease progression may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and affects mainly the spine, but can also affect other joints. Disease progression may result in loss of mobility and function. Sulfasalazine is a disease-modifying antirheumatic drug used in the treatment of AS. However, its efficacy remains unclear. This is an update of a Cochrane review first published in 2005.
OBJECTIVES
To evaluate the benefits and harms of sulfasalazine for the treatment of ankylosing spondylitis (AS).
SEARCH METHODS
We searched for relevant randomized and quasi-randomized trials in any language, using the following sources: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 11); MEDLINE (2003 to 28 November 2013); EMBASE (2003 to 27 November 2013); CINAHL (2003 to 28 November 2013); Ovid MEDLINE data, World Health Organization International Clinical Trials Registry Platform (28 November 2013); and the reference sections of retrieved articles.
SELECTION CRITERIA
We evaluated randomized and quasi-randomized trials examining the benefits and harms of sulfasalazine on AS.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed unblinded trial reports according to the selection criteria. Disagreements on the inclusion of the studies were resolved, when necessary, by recourse to a third review author. The same authors independently assessed the risk of bias of included trials and entered the data extracted from the included trials. We combined results using mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data.We restructured outcome measures for this update based on recommendations from the editorial group. Major outcomes included: pain, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis metrology index (BASMI), radiographic progression, total number of withdrawals due to adverse events, and serious adverse events.
MAIN RESULTS
We did not add any new studies to this review following the updated search. In the original review, we included 11 studies in the analysis, involving 895 participants in total. All included studies compared sulfasalazine with placebo. We judged most of the studies as low risk of bias or unclear risk of bias in five domains (random sequence generation, allocation concealment, blinding of outcome assessment, selective reporting, and other sources of bias). However, for incomplete outcome data, we only judged one trial at low risk of bias.None of the included trials assessed BASDAI, BASFI, BASMI or radiographic progression. Different parameters were used to assess pain. The pooled MD for back pain measured on a 0 to 100 mm visual analogue scale was -2.96 (95% confidence interval (CI) -6.33 to 0.41; absolute risk difference 3%, 95% CI 1% to 6%; 6 trials). Compared to placebo, a significantly higher rate of withdrawals due to adverse effects (RR 1.50, 95% CI 1.04 to 2.15; absolute risk difference 4%, 95% CI 0.4% to 8.8%; 11 trials) was found in the sulfasalazine group. A serious adverse reaction was reported in one patient taking sulfasalazine (Peto odds ratio 7.50, 95% CI 0.15 to 378.16).
AUTHORS' CONCLUSIONS
There is not enough evidence to support any benefit of sulfasalazine in reducing pain, disease activity, radiographic progression, or improving physical function and spinal mobility in the treatment of AS. A statistically significant benefit in reducing the erythrocyte sedimentation rate and easing spinal stiffness was mentioned in the previous version. However, the effect size was very small and not clinically meaningful. More withdrawals because of side effects occurred with sulfasalazine. Further studies, with larger sample sizes, longer duration, and using validated outcome measures are needed to verify the uncertainty of sulfasalazine in AS.
Topics: Antirheumatic Agents; Humans; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing; Sulfasalazine
PubMed: 25427435
DOI: 10.1002/14651858.CD004800.pub3 -
Alimentary Pharmacology & Therapeutics Jan 2003: To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations... (Review)
Review
AIM
: To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations (Asacol, Salofalk, Mesasal, Claversal, Pentasa) and pro-drugs (sulfasalazine, olsalazine, balsalazide) used in the management of ulcerative colitis.
METHODS
: Selected articles had: (1) adult healthy volunteers or patients with ulcerative colitis and (2) quantification of pharmacokinetic data to include, at a minimum, urinary excretion of total 5ASA [5ASA plus N-Acetyl-5ASA (N-Ac-5ASA)].
DATA COLLECTION AND ANALYSIS
: Pharmacokinetic data (Tmax, Cmax, AUC, urinary excretion, faecal excretion) of 5ASA, its major metabolite N-Acetyl-5ASA, total 5ASA, and the parent pro-drug compounds was extracted.
MAIN RESULTS
: The summary results for urinary excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 11-33% or median 22%; olsalazine mean 14-31% or median 16-27%; balsalazide mean 12-35% or median 20%; Asacol mean 10-35% or median 18-40%; Pentasa mean 15-53% or median 23-34%; Salofalk, Mesasal and Claversal mean 27-56% or median 31-44%. The summary results for faecal excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 23-75% or median 38%; olsalazine mean 47-50% or median 17-36%; balsalazide mean 46% or median 22%; Asacol mean 40-64% or median 20-56%; Pentasa mean 12-51% or median 39-59%; Salofalk, Mesasal and Claversal mean 37-44% or median 23-35%.
CONCLUSIONS
: The systemic exposure to 5ASA, as measured by urinary excretion of total 5ASA, and the faecal excretion of total 5ASA is comparable for all oral mesalazine formulations and pro-drugs. Thus, selection of a mesalazine therapy for the treatment of ulcerative colitis should be based on other factors such as efficacy, dose-response, toxicity of the parent compound and its metabolites, compliance issues related to dose forms and dosing schedules, and costs.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Feces; Humans; Mesalamine; Prodrugs
PubMed: 12492730
DOI: 10.1046/j.1365-2036.2003.01408.x -
The American Journal of Gastroenterology Apr 2011Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Evidence for treatment with 5-aminosalicylic acid (5-ASA) drugs is conflicting. We... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Evidence for treatment with 5-aminosalicylic acid (5-ASA) drugs is conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine this issue.
METHODS
MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Authors of studies were contacted to provide additional information on trials where required, and experts in the field were contacted to identify unpublished studies. Eligible trials recruited adults with active or quiescent CD and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active CD, and RR of relapse of disease activity in quiescent CD, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference.
RESULTS
The search identified 3,061 citations. Twenty-two RCTs were eligible. Six RCTs compared 5-ASA with placebo in active CD remission. There was a trend towards a benefit with sulfasalazine over placebo (two RCTs, RR of failure to achieve remission=0.83; 95% CI=0.69-1.00), but no definite benefit of mesalamine over placebo (four RCTs, RR=0.91; 95% CI=0.77-1.06). Neither sulfasalazine nor mesalamine were effective in preventing quiescent CD relapse, but in a per protocol analysis mesalamine appeared to reduce risk of relapse (RR=0.79; 95% CI=0.66-0.95, NNT=13).
CONCLUSIONS
The role of 5-ASAs in inducing remission of active CD and preventing relapse of quiescent CD remains uncertain, and more RCTs are required.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Crohn Disease; Humans; Mesalamine; Randomized Controlled Trials as Topic; Remission Induction; Risk Reduction Behavior; Secondary Prevention; Sulfasalazine; Treatment Outcome
PubMed: 21407190
DOI: 10.1038/ajg.2011.71 -
Drugs Feb 2015While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established. (Review)
Review
BACKGROUND
While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established.
OBJECTIVES
The objective of this systematic review is to assess the literature on the efficacy and safety of interventions for the treatment of pemphigus vulgaris.
DATA SOURCES
Five electronic databases were searched, including The Cochrane Skin Group's Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE and Latin American and Caribbean Health science Information database (LILACS). Five trial registers as well as reference lists of included RCTs were also searched.
STUDY ELIGIBILITY CRITERIA
Any published randomised controlled trial (RCT) on intervention for pemphigus vulgaris was included, provided the diagnosis of pemphigus vulgaris was confirmed with appropriate clinical features, histopathology and immunofluorescence studies. Studies which included forms of pemphigus other than pemphigus vulgaris were excluded.
INTERVENTIONS
Altogether 18 RCTs were identified including 16 distinct interventions.
STUDY APPRAISAL AND SYNTHESIS METHODS
Included studies were assessed for patient selection, methods of randomisation, blinding, follow-up and selective reporting.
RESULTS
Current evidence is incomplete and inconclusive. The interventions which appear promising, but will require further evaluation include adjuvant mycophenolate mofetil (MMF), azathioprine, intravenous immunoglobulins (IVIG), sulfasalazine and pentoxifylline, infliximab, epidermal growth factor and pimecrolimus. Interventions with inconclusive evidence include high (120-180 mg) versus low (45-60 mg) prednisone dosage, pulsed dexamethasone, cyclophosphamide, dexamethasone-cyclophosphamide pulse therapy (DCP), cyclosporine, dapsone, etanercept, acyclovir and tacrolimus.
LIMITATIONS
Our review is limited by the small number of high-quality RCTs and variety of outcome measures, precluding the performing of a meta-analysis.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The optimal treatment strategy for pemphigus vulgaris remains unclear. Higher quality RCTs are required in the future to re-evaluate many interventions and to explore other unstudied interventions.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Immunologic Factors; Pemphigus; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25655250
DOI: 10.1007/s40265-015-0353-6 -
The Journal of Rheumatology Apr 2006To evaluate the efficacy and toxicity of sulfasalazine (SSZ) for the treatment of ankylosing spondylitis (AS). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and toxicity of sulfasalazine (SSZ) for the treatment of ankylosing spondylitis (AS).
METHODS
We searched randomized and quasi-randomized trials in any language comparing SSZ with placebo in treatment of AS. Two reviewers independently selected the studies and assessed the methodological quality. Data were extracted from the chosen studies and metaanalysis was conducted with RevMan software.
RESULTS
We identified 11 trials, in which a total of 895 patients were treated for periods ranging from 12 weeks to 3 years. The pooled analysis showed that differences between SSZ and placebo were statistically significant only in erythrocyte sedimentation rate (ESR) and the severity of spinal stiffness, favoring SSZ over placebo. Weighted mean differences were ESR -4.79 mm/h (95% CI -8.80 to -0.78) and spine stiffness -13.89 mm (95% CI -22.54 to -5.24) on 100 mm visual analog scale (where 0 = no stiffness, 100 = severe stiffness). Nissila 1988 is the only trial in which SSZ showed benefit in primary outcome analyses, including back pain, chest expansion, occiput-to-wall test, and patient's general well-being. Compared with other trials, patients in this trial had the shortest disease duration and highest level of baseline ESR, and it had the greatest proportion of patients with peripheral arthritis. Significantly more withdrawals for side effects (relative risk 1.47, 95% CI 1.01 to 2.13) were found in the SSZ than in the placebo group, although severe side effects were rare.
CONCLUSION
Across all patients with AS, SSZ showed some benefit in reducing ESR and easing spinal stiffness, but no evidence of benefit in physical function, pain, spinal mobility, enthesitis, or patient and physician global assessment. Patients at an early stage of disease, with higher level of ESR (or active disease) and peripheral arthritis, might benefit from SSZ.
Topics: Antirheumatic Agents; Blood Sedimentation; Humans; Randomized Controlled Trials as Topic; Range of Motion, Articular; Spine; Spondylitis, Ankylosing; Sulfasalazine; Treatment Outcome
PubMed: 16583475
DOI: No ID Found -
The Cochrane Database of Systematic... 2000To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA). (Review)
Review
OBJECTIVES
To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA).
SEARCH STRATEGY
We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles.
SELECTION CRITERIA
All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing sulfasalazine against placebo in patients with RA.
DATA COLLECTION AND ANALYSIS
Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the RCTs and CCTs independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity.
MAIN RESULTS
Six trials, including 468 patients were included. A statistically significant benefit was observed for sulfasalazine when compared to placebo for tender and swollen joint scores, pain and ESR. The standardized weighted mean difference between treatment and placebo was -0.49 for tender and swollen joint scores, and -0.42 for pain. The difference for ESR was -17.6mm. Withdrawals from adverse reactions were significantly higher in the sulfasalazine group (OR=3.0). Patients receiving placebo were four times more likely to discontinue treatment because of lack of efficacy than patients receiving sulfasalazine.
REVIEWER'S CONCLUSIONS
Sulfasalazine appears to have a clinically and statistically significant benefit on the disease activity of patients with RA. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Sulfasalazine
PubMed: 10796400
DOI: 10.1002/14651858.CD000958