love copy van cleef & arpels alhambra bracelet do you want it? from loersertydass's blog
Methotrexate use and risk of lung disease in psoriasis
AbstractObjective To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.Study selection Double blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease. Heterogeneity across the studies was not significant (I2=0%), allowing combination of trial results. 504 respiratory adverse events were documented in 1630 participants. Methotrexate was not associated with an increased risk of adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to 1.17), respiratory infections (1.02, 0.88 to 1.19), or non infectious respiratory events (1.07, 0.58 to 1.96). No pulmonary deaths occurred.Conclusions Findings suggested that there was no increased risk of lung disease in methotrexate treated patients with non malignant inflammatory diseases. Given the limitations of the study, however, we cannot exclude a small but clinically important risk.IntroductionMethotrexate is an effective treatment for malignant as well as several non malignant inflammatory diseases.1 It is recommended as a first line disease modifying treatment for rheumatoid arthritis,2 3 psoriatic arthritis, and psoriasis,4 5 6 and for both the induction and maintenance of remission in Crohn's disease.7 Methotrexate may be used as monotherapy or in combination with other drugs, including oral agents and newer biologicals.2 3 4 5 6 7 In some disorders methotrexate is not only disease altering but also life saving.8 9Methotrexate has been implicated as a cause of serious lung toxicity.1 2 3 6 The prevalence of methotrexate related interstitial lung disease remains unknown but has been reported to be as high as 11.6% in rheumatoid arthritis.10 Studies of methotrexate induced lung disease among rheumatoid arthritis populations are confounded by the propensity to develop pulmonary infections and pulmonary manifestations of rheumatoid arthritis itself, concomitant drug use, and a higher rate of pulmonary fatalities.11 12 13 Distinguishing between rheumatoid arthritis related and methotrexate related interstitial lung disease is difficult if not impossible since the clinical and histological features overlap.14 15 16 Aside from case reports, all previous studies of methotrexate related interstitial lung disease have been in rheumatoid arthritis.A recent meta analysis of clinical trials of rheumatoid arthritis reported a small but significant increase in infectious respiratory complications but no increase in non infectious events among participants treated with methotrexate.17 Studies of clinical trials among diseases without pulmonary manifestations provide an opportunity to evaluate this problem more clearly.We performed a meta analysis of randomised controlled trials of 12 weeks or greater duration to evaluate if methotrexate fake bracelet alhambra van cleef is associated with an increased risk of lung disease in adults with psoriasis, psoriatic arthritis, and inflammatory bowel disease.MethodsData sources and searchesWe carried out a systematic literature search with no date limits using PubMed, the Cochrane central register of controlled trials, and Embase. The search was performed to 9 January 2014 (see supplementary file for keywords used in search strategy). We also searched for previously published meta analyses and systematic literature reviews. The reference lists of relevant articles were also reviewed.The inclusion criteria for study selection were: double blind randomised controlled trials; patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease; studies in English; studies consisting of a minimum of two arms, at least one receiving methotrexate and at least one not receiving methotrexate; studies including only adults (18 years); trials of 12 weeks or more duration; studies of 50 patients or more; and studies reporting respiratory side effects for methotrexate and comparator groups separately. In the case of multiple publications of one randomised controlled trial we included the publication most relevant to our inclusion criteria, in terms of detailed reporting of respiratory side effects. If the results of a study were reported at multiple time points, we included the publication of greatest duration provided it remained a double blind randomised controlled trial and fully reported respiratory adverse events. If required we reviewed previous publications of the same trial to fully assess the trial protocol and risk of bias. This approach was taken to avoid including participants more than once in the meta analysis.We selected relevant articles using a two step approach. Firstly, we screened the titles and abstracts of identified references to exclude articles that did not deal with the topic of interest. Secondly, we reviewed the full text of relevant articles. Adverse events were extracted as both total respiratory adverse events and individual adverse events in each category reported in any individual trial. The terminology used to describe respiratory adverse events varied widely in the included studies; to overcome the lack of standardisation in terminology used, we classified adverse events into two subgroups: infectious adverse events and non infectious adverse events.Data synthesis and analysisWe meta analysed data using RevMan Version 5.1 software,18 expressed as relative risk for dichotomous variables. Throughout we used random effects meta analysis using the Mantel Haenszel method. Results are expressed as relative risks with 95% confidence intervals. Discrepancies were resolved by discussion and consensus. A risk of bias graph and summary were generated. We generated funnel plots to assess for publication bias.Sensitivity analysisWe performed sensitivity analysis to assess the effect of trial size (ResultsLiterature searchFrom the literature search 3188 citations were identified: 2968 from PubMed, 162 from the Cochrane central register of controlled trials, and 58 from Embase. Of the 3188 studies, only seven articles met the predefined inclusion criteria and were included in the knock off van cleef & arpels bracelet meta analysis (fig 1).Fig 1 Flow of studies through reviewStudy characteristicsThe seven included studies comprised 1640 patients, 818 of whom received methotrexate and 812 comparator treatments (table 1). The study durations ranged from 16 to 52 weeks and the number of patients from 76 to 478. The studies reported a total of 946 patient years of exposure. Five studies involved placebo comparators only, one a monoclonal antibody alone, and one placebo and monoclonal antibody comparator groups.20 21 22 23 24 25 26Table 1 Characteristics of studies included in meta analysisView this table:View popupView inlineFindingsOverall, 504 respiratory adverse events were documented (table 2). Although the I2 index was low (0%), the type and number of respiratory adverse events reported varied considerably between the studies so we chose a random effects model for our analyses. Overall, methotrexate was not associated with an increased risk of total adverse respiratory events compared with comparator agents (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%, fig 2). In addition we found no increased risk in infectious respiratory events (1.02, 0.88 to 1.19, I2=0%) nor non infectious replica van cleef and arpels clover bracelet respiratory adverse events (1.07, 0.58 to 1.96, I2=0%) (see supplementary figures 1 and 2). No pulmonary deaths occurred. A single case of pneumonitis was reported in a patient treated with methotrexate in one study, but no definitive diagnostic features or additional information were reported.20Risk of bias in included studiesA risk of bias graph, risk of bias summary, and funnel plot suggested a low risk of bias (see supplementary figures 3 5). Three of the studies provided inadequate information to assess the risk of selection bias.Sensitivity analysisAdditional subgroup analyses showed no effect of study size, disease under study, comparator treatment, study drop out rate, use of folic acid supplementation, or difference between methotrexate naive patients and those who had previously received methotrexate (table 3). Two additional studies with fewer than 50 patients were identified; they reported no additional respiratory adverse events and their inclusion did not change the results of the analyses (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%) (see supplementary figure 6).
AbstractObjective To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.Study selection Double blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease. Heterogeneity across the studies was not significant (I2=0%), allowing combination of trial results. 504 respiratory adverse events were documented in 1630 participants. Methotrexate was not associated with an increased risk of adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to 1.17), respiratory infections (1.02, 0.88 to 1.19), or non infectious respiratory events (1.07, 0.58 to 1.96). No pulmonary deaths occurred.Conclusions Findings suggested that there was no increased risk of lung disease in methotrexate treated patients with non malignant inflammatory diseases. Given the limitations of the study, however, we cannot exclude a small but clinically important risk.IntroductionMethotrexate is an effective treatment for malignant as well as several non malignant inflammatory diseases.1 It is recommended as a first line disease modifying treatment for rheumatoid arthritis,2 3 psoriatic arthritis, and psoriasis,4 5 6 and for both the induction and maintenance of remission in Crohn's disease.7 Methotrexate may be used as monotherapy or in combination with other drugs, including oral agents and newer biologicals.2 3 4 5 6 7 In some disorders methotrexate is not only disease altering but also life saving.8 9Methotrexate has been implicated as a cause of serious lung toxicity.1 2 3 6 The prevalence of methotrexate related interstitial lung disease remains unknown but has been reported to be as high as 11.6% in rheumatoid arthritis.10 Studies of methotrexate induced lung disease among rheumatoid arthritis populations are confounded by the propensity to develop pulmonary infections and pulmonary manifestations of rheumatoid arthritis itself, concomitant drug use, and a higher rate of pulmonary fatalities.11 12 13 Distinguishing between rheumatoid arthritis related and methotrexate related interstitial lung disease is difficult if not impossible since the clinical and histological features overlap.14 15 16 Aside from case reports, all previous studies of methotrexate related interstitial lung disease have been in rheumatoid arthritis.A recent meta analysis of clinical trials of rheumatoid arthritis reported a small but significant increase in infectious respiratory complications but no increase in non infectious events among participants treated with methotrexate.17 Studies of clinical trials among diseases without pulmonary manifestations provide an opportunity to evaluate this problem more clearly.We performed a meta analysis of randomised controlled trials of 12 weeks or greater duration to evaluate if methotrexate fake bracelet alhambra van cleef is associated with an increased risk of lung disease in adults with psoriasis, psoriatic arthritis, and inflammatory bowel disease.MethodsData sources and searchesWe carried out a systematic literature search with no date limits using PubMed, the Cochrane central register of controlled trials, and Embase. The search was performed to 9 January 2014 (see supplementary file for keywords used in search strategy). We also searched for previously published meta analyses and systematic literature reviews. The reference lists of relevant articles were also reviewed.The inclusion criteria for study selection were: double blind randomised controlled trials; patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease; studies in English; studies consisting of a minimum of two arms, at least one receiving methotrexate and at least one not receiving methotrexate; studies including only adults (18 years); trials of 12 weeks or more duration; studies of 50 patients or more; and studies reporting respiratory side effects for methotrexate and comparator groups separately. In the case of multiple publications of one randomised controlled trial we included the publication most relevant to our inclusion criteria, in terms of detailed reporting of respiratory side effects. If the results of a study were reported at multiple time points, we included the publication of greatest duration provided it remained a double blind randomised controlled trial and fully reported respiratory adverse events. If required we reviewed previous publications of the same trial to fully assess the trial protocol and risk of bias. This approach was taken to avoid including participants more than once in the meta analysis.We selected relevant articles using a two step approach. Firstly, we screened the titles and abstracts of identified references to exclude articles that did not deal with the topic of interest. Secondly, we reviewed the full text of relevant articles. Adverse events were extracted as both total respiratory adverse events and individual adverse events in each category reported in any individual trial. The terminology used to describe respiratory adverse events varied widely in the included studies; to overcome the lack of standardisation in terminology used, we classified adverse events into two subgroups: infectious adverse events and non infectious adverse events.Data synthesis and analysisWe meta analysed data using RevMan Version 5.1 software,18 expressed as relative risk for dichotomous variables. Throughout we used random effects meta analysis using the Mantel Haenszel method. Results are expressed as relative risks with 95% confidence intervals. Discrepancies were resolved by discussion and consensus. A risk of bias graph and summary were generated. We generated funnel plots to assess for publication bias.Sensitivity analysisWe performed sensitivity analysis to assess the effect of trial size (ResultsLiterature searchFrom the literature search 3188 citations were identified: 2968 from PubMed, 162 from the Cochrane central register of controlled trials, and 58 from Embase. Of the 3188 studies, only seven articles met the predefined inclusion criteria and were included in the knock off van cleef & arpels bracelet meta analysis (fig 1).Fig 1 Flow of studies through reviewStudy characteristicsThe seven included studies comprised 1640 patients, 818 of whom received methotrexate and 812 comparator treatments (table 1). The study durations ranged from 16 to 52 weeks and the number of patients from 76 to 478. The studies reported a total of 946 patient years of exposure. Five studies involved placebo comparators only, one a monoclonal antibody alone, and one placebo and monoclonal antibody comparator groups.20 21 22 23 24 25 26Table 1 Characteristics of studies included in meta analysisView this table:View popupView inlineFindingsOverall, 504 respiratory adverse events were documented (table 2). Although the I2 index was low (0%), the type and number of respiratory adverse events reported varied considerably between the studies so we chose a random effects model for our analyses. Overall, methotrexate was not associated with an increased risk of total adverse respiratory events compared with comparator agents (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%, fig 2). In addition we found no increased risk in infectious respiratory events (1.02, 0.88 to 1.19, I2=0%) nor non infectious replica van cleef and arpels clover bracelet respiratory adverse events (1.07, 0.58 to 1.96, I2=0%) (see supplementary figures 1 and 2). No pulmonary deaths occurred. A single case of pneumonitis was reported in a patient treated with methotrexate in one study, but no definitive diagnostic features or additional information were reported.20Risk of bias in included studiesA risk of bias graph, risk of bias summary, and funnel plot suggested a low risk of bias (see supplementary figures 3 5). Three of the studies provided inadequate information to assess the risk of selection bias.Sensitivity analysisAdditional subgroup analyses showed no effect of study size, disease under study, comparator treatment, study drop out rate, use of folic acid supplementation, or difference between methotrexate naive patients and those who had previously received methotrexate (table 3). Two additional studies with fewer than 50 patients were identified; they reported no additional respiratory adverse events and their inclusion did not change the results of the analyses (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%) (see supplementary figure 6).
The Wall