-
The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
The Cochrane Database of Systematic... Jul 2019Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened...
BACKGROUND
Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened cutaneous areas. Morphea has different clinical features according to the subtype and stage of evolution of the disease. There is currently no consensus on optimal interventions for morphea.
OBJECTIVES
To assess the effects of treatments for people with any form of morphea.
SEARCH METHODS
We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and five trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical, intralesional, or systemic treatments (isolated or combined) in anyone who has been clinically diagnosed by a medical practitioner with any form of morphea. Eligible controls were placebo, no intervention, any other treatment, or different doses or duration of a treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were global improvement of disease activity or damage assessed by a medical practitioner or by participants, and adverse effects. Secondary outcomes were improvement of disease activity and improvement of disease damage. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
We included 14 trials, with a total of 429 randomised participants, aged between 3 and 76 years. There were juvenile and adult participants; over half were female, and the majority had circumscribed morphea, followed by linear scleroderma. The settings of the studies (where described) included a dermatologic centre, a national laboratory centre, paediatric rheumatology and dermatology centres, and a university hospital or medical centre.The studies evaluated heterogenous therapies for different types of morphea, covering a wide range of comparisons. We were unable to conduct any meta-analyses. Seven studies investigated topical medications, two evaluated intralesional medications, and five investigated systemic medications. The study duration ranged from seven weeks to 15 months from baseline.We present here results for our primary outcomes for our four key comparisons. All of these results are based on low-quality evidence.The included studies were at high risk of performance, detection, attrition, and reporting bias.Global improvement of disease activity or damage after treatment may be higher with oral methotrexate (15 mg/m², maximum 20 mg, once a week, for 12 months or until disease flare) plus oral prednisone (1 mg/kg a day, maximum of 50 mg, in a single morning dose, for three months, and one month with gradually decreased dose until discontinuation) than with placebo plus oral prednisone in children and adolescents with active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed) (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.20 to 4.45; number needed to treat for an additional beneficial outcome (NNTB) 3; 1 randomised controlled trial (RCT); 70 participants, all juvenile). This outcome was measured 12 months from the start of treatment or until flare of the disease. Data were not available separately for each morphea type. There may be little or no difference in the number of participants experiencing at least one adverse event with oral methotrexate (26/46) or placebo (11/24) (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT; 70 participants assessed during the 12-month follow-up). Adverse events related to methotrexate included alopecia, nausea, headache, fatigue and hepatotoxicity, whilst adverse events related to prednisone (given in both groups) included weight gain (more than 5% of body weight) and striae rubrae.One three-armed RCT compared the following treatments: medium-dose (50 J/cm²) UVA-1; low-dose (20 J/cm²) UVA-1; and narrowband UVB phototherapy. There may be little or no difference between treatments in global improvement of disease activity or damage, as assessed through the modified skin score (where high values represent a worse outcome): medium-dose UVA-1 phototherapy versus low-dose UVA-1 group: MD 1.60, 95% CI -1.70 to 4.90 (44 participants); narrowband UVB phototherapy versus medium-dose UVA-1 group: MD -1.70, 95% CI -5.27 to 1.87 (35 participants); and narrowband UVB versus low-dose UVA-1 group: MD -0.10, 95% CI -2.49 to 2.29 (45 participants). This RCT included children and adults with active morphea (circumscribed morphea, linear scleroderma (with trunk/limb variant and head variant), generalised morphea, or mixed morphea), who received phototherapy five times a week, for eight weeks. Outcomes were measured at eight weeks from the start of treatment.Safety data, measured throughout treatment, from the same RCT (62 participants) showed that treatment with UVA-1 phototherapy may cause mild tanning compared to narrowband UVB: narrowband UVB versus medium-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.42; 35 participants; narrowband UVB versus low-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.41; 45 participants. However, there may be no difference in the number of participants reporting mild tanning when comparing medium and low dose UVA-1 phototherapy (RR 1.00, 95% CI 0.91 to 1.10; 44 participants). Transient erythema was reported in three participants with narrowband UVB and no participants in the low- or medium-dose UVA-1 groups.
AUTHORS' CONCLUSIONS
Compared to placebo plus oral prednisone, oral methotrexate plus oral prednisone may improve disease activity or damage in juvenile active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed), but there may be a slightly increased chance of experiencing at least one adverse event.When medium-dose UVA-1 (50 J/cm²), low-dose UVA-1 (20 J/cm²), and narrowband UVB were compared against each other in treating children and adults with active morphea (circumscribed morphea, linear scleroderma, generalised morphea and mixed morphea), there may be little or no difference between these treatments on global improvement of disease activity or damage. UVA-1 phototherapy may cause more mild tanning than narrowband UVB, but there may be no difference between medium- and low-dose UVA-1 phototherapy. These results are based on low-quality evidence.Limitations of data and analyses include risk of bias and imprecision (small number of participants or events and wide confidence intervals). We encourage multicentre RCTs to increase sample size and evaluate, with validated tools, different treatment responses according to the subtypes of morphea and age groups.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Male; Methotrexate; Middle Aged; Phototherapy; Prednisone; Randomized Controlled Trials as Topic; Scleroderma, Localized; Young Adult
PubMed: 31309547
DOI: 10.1002/14651858.CD005027.pub5 -
The World Journal of Biological... Mar 2024Corticosteroids are widely prescribed for a variety of medical conditions. Accumulating evidence suggests that their use may be associated with adverse psychiatric... (Review)
Review
OBJECTIVES
Corticosteroids are widely prescribed for a variety of medical conditions. Accumulating evidence suggests that their use may be associated with adverse psychiatric effects, including mania. In this systematic review, we aim to critically evaluate the existing literature on the association between corticosteroid use and the emergence of mania.
METHODS
We conducted a comprehensive search of major electronic databases (PubMed, Embase, Cochrane Library) for relevant studies published up to the date of the search (12th January 2023). Inclusion criteria involve studies that investigate the association between corticosteroid use and the emergence of mania in adult patients. The primary outcome is the prevalence of (hypo)mania following corticosteroid administration. Secondary outcomes include potential risk factors, dose-response relationships, and differences among various corticosteroid formulations.
RESULTS
The identified studies were subjected to a systematic selection process and data extraction by an independent reviewer. A total of 47 articles met the inclusion criteria for our systematic review.
CONCLUSION
Our findings suggest that mania is a common side-effect of corticosteroid use, particularly in prednisone equivalent doses above 40 mg. These findings hold practical significance for clinicians and provide insights into potential interventions, including careful monitoring, dose adjustments, and consideration of psychotropic medications when managing corticosteroid-induced mania.
Topics: Adult; Humans; Mania; Adrenal Cortex Hormones; Prednisone
PubMed: 38363330
DOI: 10.1080/15622975.2024.2312572 -
Clinical and Experimental Dental... Feb 2023Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for... (Review)
Review
OBJECTIVE
Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for upper lower airways and kidneys. The etiology remains unknown although it may originate from different stimuli, in genetically susceptible patients.
MATERIALS AND METHODS
A detailed database search was performed. The variables were demographics, localization, histopathological findings, antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA) tests, treatment, and follow-up.
RESULTS
Fifty-two cases were identified; the mean age was 49.6 years, with a range from 6 to 87 years. It was most frequently seen in females (57.7%). The most common race was white (59.6%). The most frequent location was in the maxillary gingiva (28.8%), followed by both the upper and lower gingiva (19.2%). The most common clinical presentation was "strawberry gingivitis" (61.5%). The main symptom was pain, in 50%. Regarding the c-ANCA test, it was positive in 71.2% of cases. The most common therapy was prednisone and cyclophosphamide, utilized in 51.9%. The average follow-up was 23.6 months, and 88.5% of patients were still alive at follow-up.
CONCLUSION
The diagnosis initially was difficult to establish, an early diagnosis and treatment are mandatory. If untreated the disease can be associated with morbidity and mortality. For the oral clinician, this disease needs to be addressed in the differential diagnosis of oral lesions.
Topics: Female; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide
PubMed: 36600477
DOI: 10.1002/cre2.706 -
Journal of Child and Adolescent... Apr 2023Knowledge is limited regarding the adverse effects of therapeutic glucocorticoids on pediatric mental health outcomes. Glucocorticoid-induced psychosis (GIP) is a rare... (Review)
Review
Knowledge is limited regarding the adverse effects of therapeutic glucocorticoids on pediatric mental health outcomes. Glucocorticoid-induced psychosis (GIP) is a rare but severe side effect of high-dose glucocorticoid therapy in children and adolescents. This study identified reported pediatric cases of GIP, based on DSM-5 criteria, and defined its presentation, treatments, and outcomes. A systematic review was completed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including pediatric patients with incident psychosis following glucocorticoid treatment. Patient demographics, clinical presentation, interventions, outcomes, and long-term management were extracted from individual cases. Of 1131 articles screened, 28 reports were included, comprising of 31 patients. The mean age was 13 years, and 61% of patients were male. The most common medical illnesses requiring administration of high dose glucocorticoids were asthma (23%) and acute lymphoblastic leukemia (23%). The most common glucocorticoid used was prednisone (35%), and most patients (91%) received doses greater than or equal to 40 mg/day of prednisone. The range of time to symptom onset was 1 day to 7 months. Hallucinations alone (45%) were the most reported feature of GIP. Glucocorticoids were discontinued in 52% of cases, reduced in dosage in 32%, and 81% of affected patients were prescribed psychotropic medications. Long-term management plans and prophylactic psychotropic use were not mentioned in 52% of cases. Symptoms resolved in 90% of patients, and the majority (71%) had no recurrence of psychiatric symptoms. GIP can generally be managed by tapering the causative agent with adjunctive second-generation antipsychotics if psychotic symptoms persist. All patients in this review had complete resolution or improvement of their psychotic symptoms; however, there is likely reporting bias due to the expected underreporting of negative outcomes. Managing clinicians must take a circumspect approach when prescribing high-dose glucocorticoids to minimize the risk of serious but preventable side effects.
Topics: Child; Humans; Adolescent; Male; Female; Glucocorticoids; Prednisone; Psychotic Disorders; Antipsychotic Agents; Psychotropic Drugs
PubMed: 37074331
DOI: 10.1089/cap.2022.0077 -
Journal of Clinical and Experimental... Jan 2023Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A... (Review)
Review
BACKGROUND
Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A variety of topical and systemic therapies have been tried to restore/stimulate the gland function or replace saliva reducing the symptoms of xerostomia and to avoid the problems of diminished salivary flow.
MATERIAL AND METHODS
Four search engines (PUBMED/Medline, EMBASE, Google Scholar and The Cochrane) were used in conducting a systematic review using the terms "Sjogren's syndrome" with the combination of other terms. To define these study acceptability criteria, we used PICO model (Population, Intervention, Control and Outcome) and study design technique.
RESULTS
Out of 47 articles initially screened, 28 studies met our selection criteria. Included studies showed positive results with interventions such as pilocarpine, rituximab, and interferon-alpha (IFN-α) for enhancing salivary flow and lacrimal secretion in SS condition. One study showed promising results for combination of prednisone and hydroxychloroquine in SS, however dose of prednisone is recommended to be tapered. Another study demonstrated comparable effects of dehydroepiandrosterone and the placebo in alleviation of dry mouth symptoms (=0.006). Therapeutic effects have been reported with LASER therapy.
CONCLUSIONS
Pilocarpine was found to be highly beneficial whereas, rituximab and IFN-α were moderately effective in the reduction of hyposalivation in SS patient. Adverse events were common. Use of any alternative modalities for the management cannot be supported based on the current evidence; this demands more studies in future to be conducted staking into account adverse effects which might occur particularly with the pharmacological therapies. Sjogren's Syndrome, Xerostomia, Hyposalivation, Pilocarpine, Rituximab, Sialagogue.
PubMed: 36755678
DOI: 10.4317/jced.59891 -
The Cochrane Database of Systematic... May 2022Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (250 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants) but not tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. Across comparison groups, the same study found no evidence of a difference in vision changes and inconsistent evidence with regard to quality of life. Evidence on quality of life as assessed by the physical (MD 8.17, 95% CI 4.44 to 11.90) and mental (MD 5.61, 95% CI 0.06 to 11.16) component score of the 36-Item Short Form Health Survey (SF-36) favored weekly tocilizumab versus placebo + 52-week taper but not bi-weekly tocillizumab versus placebo + 26-week taper (moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal, Humanized; Female; Giant Cell Arteritis; Humans; Male; Recurrence
PubMed: 35560150
DOI: 10.1002/14651858.CD013484.pub3 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Rheumatology (Oxford, England) Aug 2023The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA.
METHODS
A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE).
RESULTS
Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19-1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: -0.23; -0.43 to -0.03), function (HAQ -0.09; -0.18 to 0.00), and Larsen scores (-4.61; -7.52 to -1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs.
CONCLUSION
There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties.
Topics: Humans; Glucocorticoids; Arthritis, Rheumatoid; Prednisone; Randomized Controlled Trials as Topic
PubMed: 36810945
DOI: 10.1093/rheumatology/kead088 -
Journal of the European Academy of... Feb 2024There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is... (Review)
Review
There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence-based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk-of-bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H and/ or H -antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state-of-the-art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well-designed, high-quality interventional trials are needed to establish evidence-based treatment guidelines for AU.
PubMed: 38420865
DOI: 10.1111/jdv.19904