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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 Lancet. Rheumatology Dec 2023Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of...
BACKGROUND
Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA.
METHODS
This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up.
FINDINGS
121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab.
INTERPRETATION
These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity.
FUNDING
None.
Topics: Male; Humans; Female; Adult; Middle Aged; Retrospective Studies; Cohort Studies; Churg-Strauss Syndrome; Prednisone; Granulomatosis with Polyangiitis; Interleukin Inhibitors; Leukocyte Disorders; Pathologic Complete Response; Antibodies, Monoclonal, Humanized
PubMed: 38251561
DOI: 10.1016/S2665-9913(23)00243-6 -
Biology Aug 2023Although solid organ transplantation in persons with diabetes mellitus is often associated with hyperglycemia, the risk of hyperlipidemia in all organ transplant... (Review)
Review
Although solid organ transplantation in persons with diabetes mellitus is often associated with hyperglycemia, the risk of hyperlipidemia in all organ transplant recipients is often underestimated. The diagnosis of diabetes often predates transplantation; however, in a moderate percentage of allograft recipients, perioperative hyperglycemia occurs triggered by antirejection regimens. Post-transplant prescription of glucocorticoids, calcineurin inhibitors and mTOR inhibitors are associated with increased lipid concentrations. The existence of diabetes mellitus prior to or following a liver transplant is associated with shorter times of useful allograft function. A cycle involving Smad, TGF beta, m-TOR and toll-like receptors has been identified in the contribution of rejection and aging of allografts. Glucocorticoids (prednisone) and calcineurin inhibitors (cyclosporine and tacrolimus) induce hyperglycemia associated with insulin resistance. Azathioprine, mycophenolate and prednisone are associated with lipogenesis. mTOR inhibitors (rapamycin) are used to decrease doses of atherogenic agents used for immunosuppression. Post-transplant medication management must balance immune suppression and glucose and lipid control. Concerns regarding rejection often override those relative to systemic and organ vascular aging and survival. This review focuses attention on the underlying mechanism of relationships between glycemia/lipidemia control, transplant rejection and graft aging.
PubMed: 37759585
DOI: 10.3390/biology12091185 -
Journal of Clinical Oncology : Official... Aug 2023There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial.
PURPOSE
There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.
METHODS
Eligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points.
RESULTS
Between May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; = .55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; = .26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively.
CONCLUSION
Pembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome; Prednisone; Disease-Free Survival; Biomarkers; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37290035
DOI: 10.1200/JCO.23.00233 -
BMC Veterinary Research Jul 2023Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting...
BACKGROUND
Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting level of < 5% and high level of comfort there may be complacency and underestimation of the impact side effects of corticosteroids may have on a pet and pet owner.
OBJECTIVE
The objective of this clinical study was to describe the experience and perception of an owner who administered anti-inflammatory doses of oral prednisolone and prednisone to their dog for up to 14 days. We hypothesized dogs receiving anti-inflammatory doses of prednisone and prednisolone would experience much greater rates of side effects by day 14 then reported in current literature.
ANIMALS
There were 45 dogs initially enrolled in the study.
RESULTS
At each study point, 31 owners provided results. On day 5, 74% (23/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, polypnea and/or increased vocalization, with 11 individuals (35%) reporting these changes greatly increased. On day 14, 90% of owners (28/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, and/or polypnea as the most common changes noted. Overall, 61% (19/31) of owners reported an increase in filling of the water bowl over baseline and one-third (11/31) of pet owners reported cleaning up urinary accidents for pets who had been continent prior to the start of the study. Pet owner steroid satisfaction remained high through day 14 at 4.5/5 (1 = very unsatisfied, 5 = very satisfied).
CONCLUSION
This study highlights the impact short term anti-inflammatory doses of prednisone or prednisolone have on dog behaviour and confirms our hypothesis that by day 14, 90% of dogs experienced one or more behaviour changes, with polyuria and polydipsia most commonly reported. Adverse events were noted regardless of starting dosage or regimen. Although most pet owners expressed satisfaction with steroid treatment due to its high efficacy, 70% would select a more costly treatment if that treatment had fewer side effects.
Topics: Dogs; Animals; Prednisolone; Prednisone; Polyuria; Drug-Related Side Effects and Adverse Reactions; Hyperphagia; Polydipsia; Perception; Dog Diseases
PubMed: 37488543
DOI: 10.1186/s12917-023-03644-x -
Journal of Ayub Medical College,... 2023Primary ovarian Burkitt lymphoma (BL) is a very rare and aggressive malignancy. We report an 18-year-old female patient who presented with a large, tender abdomen, and...
Primary ovarian Burkitt lymphoma (BL) is a very rare and aggressive malignancy. We report an 18-year-old female patient who presented with a large, tender abdomen, and highly de-ranged renal and liver functions. Ultrasonography showed hepatosplenomegaly, mild ascites, dilated biliary channels and a heterogeneous pelvic mass of size ~15106.4 cm. Immunohistochemical (IHC) staining of the biopsy sample excised from the left ovary demonstrated reactivity for CD20 and CD10, and negativity for CD3, Bcl-2 and TdT. The C-myc translocation was positive in 60% of tumour cells. Moreover, the proliferation index was ~90%. These features were consistent with BL. After haemodialysis, the patient was planned for multiagent chemotherapy, including cyclophosphamide, doxorubicin, vincristine and prednisone. This case supports the hypothesis that primary ovarian BL is an aggressive malignancy that appears to respond promisingly to multi-agent chemotherapy.
Topics: Female; Humans; Adolescent; Burkitt Lymphoma; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Vincristine; Prednisone; Doxorubicin
PubMed: 38406915
DOI: 10.55519/JAMC-S4-12410 -
Hematology/oncology Clinics of North... Apr 2024No therapy in multiple myeloma has been as extensively investigated as stem cell transplantation following high-dose chemotherapy. A search of the national library of... (Review)
Review
No therapy in multiple myeloma has been as extensively investigated as stem cell transplantation following high-dose chemotherapy. A search of the national library of medicine in February 2023 revealed over 27,000 publications covering stem cell transplantation. No other treatment for multiple myeloma has been so vigorously investigated. However, given the rapid advances seen in the treatment of multiple myeloma, it is legitimate to ask whether the technique first introduced in 1983 by Thomas McIlwain still has relevance. In 1984,Barlogie introduced infusional vincristine, doxorubicin, and dexamethasone and in 1986 published a first series on high-dose therapy with autologous marrow-derived stem cells. At this point, the only available therapies were melphalan, prednisone, other intensive steroids such as methylprednisolone, and interferon. Cyclophosphamide was used both orally and parenterally. VBMCP was introduced as a combination therapy at Memorial Hospital subsequently shown not to be superior to melphalan and prednisone.
Topics: Humans; Multiple Myeloma; Melphalan; Prednisone; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Antineoplastic Combined Chemotherapy Protocols; Vincristine; Transplantation, Autologous; Dexamethasone
PubMed: 38151401
DOI: 10.1016/j.hoc.2023.12.005 -
Journal of Clinical Oncology : Official... Feb 2024We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial.
PATIENTS AND METHODS
Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis.
RESULTS
MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% 88.9%; = .013) and at EOI (93.1% 86.7%; = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% 16.0% in those receiving CHOP; < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% G-CHOP, 7.0%; R-CVP, 21.7% G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse.
CONCLUSION
MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; Gallium; Lymphoma, Follicular; Neoplasm, Residual; Prednisone; Rituximab; Vincristine
PubMed: 38096461
DOI: 10.1200/JCO.23.00838 -
Hematology/oncology Clinics of North... Aug 2023Despite the introduction of effective novel agents, chemoimmunotherapy (CIT), with its widespread use, retains relevance and is one of the 2 vastly disparate strategies... (Review)
Review
Despite the introduction of effective novel agents, chemoimmunotherapy (CIT), with its widespread use, retains relevance and is one of the 2 vastly disparate strategies to treat Waldenström macroglobulinemia (WM), the alternative being the Bruton tyrosine kinase inhibitor (BTKi)-based approach. Considerable evidence over the past decades supports the integration of the monoclonal anti-CD20 antibody, rituximab, to the CIT backbone in WM, a CD20+ malignancy. Besides substantial efficacy, the finite duration of the treatment, coupled with lower rates of cumulative and long-term, clinically significant adverse effects and greater affordability, make CIT appealing, notwithstanding the lack of quality-of-life data with such an approach in WM. A phase 3 randomized controlled trial reported substantially higher efficacy and a more favorable safety profile of the bendamustine-rituximab (BR) doublet compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) among patients with WM. Subsequent studies reaffirmed its high efficacy and tolerability, making BR the mainstay of managing treatment-naïve patients with WM. High-quality evidence supporting the use of BR over Dexamethasone, Rituximab, and Cyclophosphamide (DRC), another commonly used regimen, is lacking, as is its comparison with the continuous BTKi-based approach. However, DRC appeared less potent than BR in cross-trial comparisons and retrospective series involving treatment-naïve patients with WM. Additionally, a recent retrospective, international study demonstrated comparable outcomes with fixed-duration BR and continuous ibrutinib monotherapy among previously untreated, age-matched patients exhibiting MYD88 mutation. However, unlike ibrutinib, BR appears effective irrespective of the MYD88 mutation status. CIT, preferably BR, is well suited to serve as the control arm (comparator) regimen against which novel targeted agents may be evaluated as frontline therapies for WM in high-quality trials. Purine analog-based CIT has been extensively evaluated in WM, although its use has waned, even in the multiply relapsed patient population, as effective and safer alternatives emerge.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Myeloid Differentiation Factor 88; Retrospective Studies; Cyclophosphamide; Vincristine; Bendamustine Hydrochloride; Prednisone; Doxorubicin; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 37246086
DOI: 10.1016/j.hoc.2023.04.003 -
The Medical Letter on Drugs and... Oct 2023
Topics: Humans; Gout; Gout Suppressants
PubMed: 37871110
DOI: 10.58347/tml.2023.1688a