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The Cochrane Database of Systematic... Oct 2009Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic.
OBJECTIVES
To assess the effects of drugs for discoid lupus erythematosus.
SEARCH STRATEGY
In June 2009 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009), MEDLINE, EMBASE, LILACS, and online ongoing trials registers. The reference lists of relevant reviews were searched. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials.
SELECTION CRITERIA
We included all randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine, thalidomide, topical calcineurin blockers (pimecrolimus and tacrolimus), and biological agents (etanercept, efalizimab, infliximab, and rituximab).
DATA COLLECTION AND ANALYSIS
Two reviewers independently examined each retrieved study for eligibility.
MAIN RESULTS
Two trials involving 136 participants were included. No new trials were included in this update.In a cross-over study of 12 weeks duration, fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be better than hydrocortisone 1% cream (a mild corticosteroid) when the first arm of the trial involving 78 participants was analysed at 6 weeks. Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 0.0 to 0.34, NNT (Number needed to treat) 6).In the second trial, acitretin (50mg/day) was compared with hydroxychloroquine (400mg/day) in 58 people in a parallel trial of 8 weeks duration. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine but there was no significant difference between the 2 interventions. The adverse effects were more frequent and more severe in the acitretin group. In this trial clearing of erythema was measured and found to be better in the hydroxychloroquine group (RR 0.61, 95% CI 0.36 to 1.06).
AUTHORS' CONCLUSIONS
Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus.
Topics: Acitretin; Dermatologic Agents; Fluocinonide; Humans; Hydrocortisone; Hydroxychloroquine; Lupus Erythematosus, Discoid; Randomized Controlled Trials as Topic
PubMed: 19821298
DOI: 10.1002/14651858.CD002954.pub2 -
BMJ Clinical Evidence Jul 2009Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500... (Review)
Review
INTRODUCTION
Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the USA.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on joint symptoms (arthralgia/arthritis) and other non-organ-threatening symptoms (such as serositis and fatigue) in people with systemic lupus erythematosus? What are the effects of interventions for cutaneous involvement in people with systemic lupus erythematosus? What are the effects of treatments in people with proliferative lupus nephritis (WHO grades 3-5)? What are the effects of treatments for neuropsychiatric involvement in people with systemic lupus nephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 11 systematic reviews or RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acitretin; antipsychotic drugs; chloroquine; combination corticosteroids plus immunosuppressants; corticosteroids; hydroxychloroquine; intravenous immunoglobulin; methotrexate; non-steroidal anti-inflammatory drugs (NSAIDs); plasmapheresis; and sunblock.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Chloroquine; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis
PubMed: 21696649
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2007Some groups of people have a greater risk of developing common non-melanoma skin cancers (NMSC). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some groups of people have a greater risk of developing common non-melanoma skin cancers (NMSC).
OBJECTIVES
To evaluate interventions for preventing NMSC in people at high risk of developing NMSC.
SEARCH STRATEGY
We searched the Cochrane Skin Group Specialised Register (March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2007, MEDLINE (from 2003 to March 2007), EMBASE (from 2005 to March 2007), the metaRegister of Controlled Trials (February 2007). References from trials and reviews were also searched. Pharmaceutical companies were contacted for unpublished trials.
SELECTION CRITERIA
Randomised controlled trials of adults and children at high risk of developing NMSC.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and assessed their methodological quality.
MAIN RESULTS
We identified 10 trials (7,229 participants) that assessed a variety of interventions. One trial found T4N5 liposome lotion significantly reduced the rate of appearance of new BCCs in people with xeroderma pigmentosum. One of three trials of renal transplant recipients showed a significantly reduced risk of new NMSCs when acitretin was compared to placebo (relative risk (RR) 0.22 95% confidence interval (CI) 0.06 to 0.90) and no significant difference in risk of adverse events in two trials (RR 1.80, 95% CI 0.70 to 4.61). In three trials conducted in people with a history of NMSC, the evidence was inconclusive for the development of BCCs for retinol or isoretinoin. However the risk of a new SCC in one trial (HR 1.79, 95% CI 1.16 to 2.76) and adverse events in another trial (RR 1.76 95% CI 1.57 to 1.97) were significantly increased in the isotretinoin group compared with placebo. In one trial selenium showed a reduced risk of other types of cancer compared with placebo (RR 0.65, 95% CI 0.50 to 0.85) but also a significantly elevated risk of a new NMSC (HR 1.17 95% CI 1.02 to 1.34). The evidence for one trial of beta-carotene was inconclusive; and there was a trend towards fewer new NMSC in a trial of a reduced fat diet (RR 0.16, 95% CI 0.02 to 1.31), p=0.09.
AUTHORS' CONCLUSIONS
Some preventative treatments may benefit people at high risk of developing NMSC, but the ability to draw firm conclusions is limited by small numbers of trials, often with one trial per intervention or with inconsistent results between studies.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Neoplasms, Radiation-Induced; Randomized Controlled Trials as Topic; Risk Factors; Skin Neoplasms; Sunlight
PubMed: 17943854
DOI: 10.1002/14651858.CD005414.pub2 -
BMJ Clinical Evidence Apr 2007Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500... (Review)
Review
INTRODUCTION
Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 black women in the USA.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on joint (arthralgia/arthritis) symptoms and other non-organ-threatening symptoms such as serositis and fatigue in people with systemic lupus erythematosus? What are the effects of interventions for cutaneous involvement in people with systemic lupus erythematosus? What are the effects of treatments in people with proliferative (WHO grades 3-5) lupus nephritis? What are the effects of treatments for neuropsychiatric involvement in people with systemic lupus nephritis? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found eight systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acitretin, antipsychotic drugs, chloroquine, combination corticosteroids plus immunosuppressants, corticosteroids, hydroxychloroquine, intravenous immunoglobulin, methotrexate, non-steroidal anti-inflammatory drugs, plasmapheresis, and sun block.
Topics: China; Emotions; Lupus Erythematosus, Systemic; MEDLINE; United States; United States Food and Drug Administration
PubMed: 19454065
DOI: No ID Found -
The Journal of Rheumatology Jul 2006Very few well designed studies have evaluated the conventional systemic agents for psoriasis. This is a systematic, evidence-based review of the literature evaluating... (Review)
Review
Very few well designed studies have evaluated the conventional systemic agents for psoriasis. This is a systematic, evidence-based review of the literature evaluating both the efficacy and safety of the medications cyclosporine, methotrexate, acitretin, hydroxyurea, and 6-thioguanine. Treatment recommendations are made.
Topics: Acitretin; Clinical Trials as Topic; Cyclosporine; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Hydroxyurea; Immunosuppressive Agents; Methotrexate; Practice Guidelines as Topic; Psoriasis; Thioguanine; Treatment Outcome
PubMed: 16724368
DOI: No ID Found -
The British Journal of Dermatology Mar 2005The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in... (Review)
Review
BACKGROUND
The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest.
OBJECTIVES
The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population.
METHODS
Three electronic databases were searched for relevant trials: MEDLINE (1966-October 2003), EMBASE (1980-week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review.
RESULTS
Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up.
CONCLUSIONS
The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk-benefit ratio.
Topics: Acitretin; Administration, Oral; Humans; Organ Transplantation; Randomized Controlled Trials as Topic; Retinoids; Skin Neoplasms
PubMed: 15787821
DOI: 10.1111/j.1365-2133.2005.06347.x -
The Cochrane Database of Systematic... 2001Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat... (Review)
Review
BACKGROUND
Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic.
OBJECTIVES
To assess the effects of drugs for discoid lupus erythematosus.
SEARCH STRATEGY
We searched the Cochrane Clinical Trials Register (December 1999), MEDLINE (January 1966 to December 1999), EMBASE (January 1980 to January 2000), and the reference lists of relevant reviews. Index Medicus (1956 to 1966) was handsearched and 7 experts in the field were approached for information about unpublished trials.
SELECTION CRITERIA
Randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine and thalidomide.
DATA COLLECTION AND ANALYSIS
Two reviewers independently examined each retrieved study for eligibility.
MAIN RESULTS
Two trials involving 136 participants were included. In a cross-over study of twelve weeks duration fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be markedly better than hydrocortisone 1% cream ( a mild corticosteroid). Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 4.5 to 29.5% and NNT 6). In the second trial, hydroxychloroquine was compared with acitretin in 58 people. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine, a nonsignificant 4% absolute gain with hydroxychloroquine (95%CI -23% to 30%). The adverse effects were more frequent and more severe in the acitretin group.
REVIEWER'S CONCLUSIONS
Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus.
Topics: Dermatologic Agents; Humans; Lupus Erythematosus, Discoid; Randomized Controlled Trials as Topic
PubMed: 11279785
DOI: 10.1002/14651858.CD002954 -
Archives of Dermatology Dec 2000To examine the efficacy and tolerability of calcipotriene combined with phototherapy or systemic therapies compared with monotherapy for the treatment of chronic plaque... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To examine the efficacy and tolerability of calcipotriene combined with phototherapy or systemic therapies compared with monotherapy for the treatment of chronic plaque psoriasis.
DESIGN
Quantitative systematic review of 11 randomized controlled trials involving a total of 756 patients with plaque psoriasis.
MAIN OUTCOME MEASURES
Rate ratios (RRs) for marked improvement or clearance in patient and investigator overall assessments of response; mean difference in percentage change in Psoriasis Area and Severity Index; and RRs for clearance in patient and investigator overall assessments of response. Adverse effects were estimated with the RR and the rate difference in terms of withdrawal rate, proportion of patients experiencing adverse events, and proportion of patients with cutaneous and noncutaneous adverse effects.
RESULTS
Antipsoriatic effects of acitretin, cyclosporine, and psoralen-UV-A phototherapy were enhanced with the addition of topical calcipotriene using the Psoriasis Area and Severity Index as the outcome, but this is not translated into an increase in the number of patients who achieve at least marked improvement. At the end of treatment, the RRs for marked improvement or clearance in patient assessments were as follows: calcipotriene plus acitretin vs acitretin alone (12 weeks), 1.4 (95% confidence interval [CI], 1.0-1. 9); calcipotriene plus cyclosporine vs cyclosporine alone (6 weeks), 1.2 (95% CI, 0.9-1.6); and calcipotriene plus psoralen-UV-A vs psoralen-UV-A alone (12 weeks), 1.2 (95% CI, 0.9-1.6). Patients were also no more likely to obtain marked improvement or better with calcipotriene plus UV-B therapy than with UV-B therapy alone (RR, 1. 0; 95% CI, 0.8-1.1 at 8 weeks in the patient assessment). There is limited evidence that use of calcipotriene might reduce the cumulative exposure to phototherapy and systemic treatment. During the short duration of these trials, there were no significant differences in withdrawal rates or adverse effects between the combined regimens and their corresponding monotherapy control interventions.
CONCLUSIONS
Overall, there is insufficient evidence to support any large effects in favor of combination treatment. In the patient assessments, the results do not show an adjuvant effect, but there is some evidence that use of calcipotriene might reduce cumulative exposure to systemic therapy to obtain clearance. There were no long-term morbidity data on the effectiveness of any of the combinations studied. Given that psoriasis is a chronic recurrent disease for most patients, longer trials are needed to determine whether the addition of topical calcipotriene to systemic therapy improves the risk-benefit ratio by reducing the long-term risk of toxic effects. Equally important is the need to examine the impact of such combinations on the duration of remission after treatment.
Topics: Administration, Cutaneous; Calcitriol; Chronic Disease; Dermatologic Agents; Drug Administration Schedule; Drug Therapy, Combination; Humans; Phototherapy; Psoriasis; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 11115167
DOI: 10.1001/archderm.136.12.1536