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Journal of Cutaneous Medicine and... Nov 2023Prurigo nodularis (PN) is a debilitating inflammatory skin disease characterized by red to violaceous pruritic lesions. The goal of therapy is to break the scratch-itch... (Review)
Review
IMPORTANCE
Prurigo nodularis (PN) is a debilitating inflammatory skin disease characterized by red to violaceous pruritic lesions. The goal of therapy is to break the scratch-itch cycle. Treatment varies and often requires a multimodal approach to target both immune and neural mediated aspects of disease.
OBJECTIVES
To review the efficacy of systemic treatment used to treat PN.
EVIDENCE REVIEW
A systematic search of keywords and Medical Subject Headings was performed in Ovid MEDLINE, Embase, Scopus, and ClinicalTrials.gov. The first 200 results of an abbreviated search in Google Scholar were also included. PRISMA guidelines were followed and the review was registered on PROSPERO (CRD42023412012). GRADE criteria were used to assess articles for quality of evidence.
FINDINGS
The search resulted in 1153 articles; 382 were duplicates, 643 were irrelevant, 19 were not retrieved, 21 were abstract only, and 88 are included in this review. There were 24 studies on dupilumab, 16 on thalidomide, 8 on cyclosporin, 7 on methotrexate, 3 each on lenalidomide and aprepitant, 2 each on alitretinoin, apremilast, baricitinib, gabapentin, intravenous (IV) immunoglobulins, pregabalin, tofacitinib, and 1 each on amitriptyline, azathioprine, butorphanol, isoquercitin, IV dexamethasone-cyclophosphamide/ oral cyclophosphamide, ketotifen, metronidazole, montelukast, nalbuphine, nemolizumab, serolopitant, tacrolimus, and herose derma zima capsule.
CONCLUSIONS AND RELEVANCE
Dupilumab reduces pruritus and appearance of lesions and is associated with the fewest number of side effects. Thalidomide and pregabalin are also effective, but their long-term use is limited by muscle and nerve pain. Janus Kinase inhibitors may be beneficial, but large population studies are lacking.
Topics: Humans; Thalidomide; Prurigo; Pregabalin; Cyclosporine; Pruritus; Cyclophosphamide
PubMed: 37987710
DOI: 10.1177/12034754231211797 -
Renal Failure 2023This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
METHODS
A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
RESULTS
The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
CONCLUSIONS
Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
Topics: Humans; Lupus Nephritis; Cyclophosphamide; Induction Chemotherapy; Network Meta-Analysis; Treatment Outcome; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 38087473
DOI: 10.1080/0886022X.2023.2290365 -
Clinical Rheumatology Dec 2022Takayasu arteritis (TAK) is a less common large-vessel vasculitis which can occur in either children or adults. However, differences between pediatric-onset and... (Meta-Analysis)
Meta-Analysis Review
Takayasu arteritis (TAK) is a less common large-vessel vasculitis which can occur in either children or adults. However, differences between pediatric-onset and adult-onset TAK have not been systematically analyzed. We undertook a systematic review (pre-registered on PROSPERO, identifier CRD42022300238) to analyze differences in clinical presentation, angiographic involvement, treatments, and outcomes between pediatric-onset and adult-onset TAK. We searched PubMed (MEDLINE and PubMed Central), Scopus, major recent international rheumatology conference abstracts, Cochrane database, and clinicaltrials.gov, and identified seven studies of moderate to high quality comparing pediatric-onset and adult-onset TAK. Meta-analysis of 263 pediatric-onset and 981 adult-onset TAK suggested that constitutional features (fever, and in subgroup analyses, weight loss), hypertension, headache, and sinister features of cardiomyopathy, elevated serum creatinine, and abdominal pain were more frequent in pediatric-onset TAK, whereas pulse loss/pulse deficit and claudication (particularly upper limb claudication) were more frequent in adult-onset TAK. Hata's type IV TAK was more common in pediatric-onset TAK, and Hata's type I TAK in adult-onset TAK. Children with TAK also appeared to require more intense immunosuppression with more frequent use of cyclophosphamide, biologic DMARDs, tumor necrosis factor alpha inhibitors, and, in subgroup analyses, tocilizumab in pediatric-onset TAK than in adult-onset TAK. Surgical or endovascular procedures, remission, and risk of mortality were similar in both children and adults with TAK. No studies had compared patient-reported outcome measures between pediatric-onset and adult-onset TAK. Distinct clinical features and angiographic extent prevail between pediatric-onset and adult-onset TAK. Clinical outcomes in these subgroups require further study in multicentric cohorts.
Topics: Child; Adult; Humans; Takayasu Arteritis; Retrospective Studies; Cyclophosphamide; Immunosuppression Therapy; Antirheumatic Agents
PubMed: 35927524
DOI: 10.1007/s10067-022-06318-5 -
International Urology and Nephrology Mar 2023Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of... (Meta-Analysis)
Meta-Analysis Review
Efficacy of low or heavy rituximab‑based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis.
OBJECTIVE
Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment.
METHODS
Randomized controlled trials (RCTs) and observational studies analyzing nine therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions.
RESULTS
Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6 months (92%) and 12 months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6 months (78.8% and 65.4%, separately) and decreased at 12 months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12 months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose).
CONCLUSIONS
For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12 months was higher than that at 6 months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).
Topics: Adult; Humans; Cyclophosphamide; Cyclosporine; Glomerulonephritis, Membranous; Immunosuppressive Agents; Network Meta-Analysis; Rituximab; Tacrolimus; Treatment Outcome
PubMed: 36161550
DOI: 10.1007/s11255-022-03372-5 -
PloS One 2015To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis.
METHODS
A systematic review evaluating the efficacy and safety of leflunomide compared with cyclophosphamide in adult patients with LN was performed. Data from relevant randomized controlled trials (RCTs) performed before December 2014 was collected from several databases (PubMed, Embase, Cochrane Library, CNKI and CBM). No language restrictions were applied. Efficacy outcomes included overall remission, SLE Disease Activity Index (SLEDAI) score, 24-hour proteinuria and serum creatinine. Safety data were analyzed. The effects of treatment on these outcomes were summarized as relative risks (RRs) with 95% confidence intervals (CIs) and mean differences were pooled using a fixed or random effects model.
RESULTS
Eleven RCTs with Jadad score of 3 or greater were identified and included a total of 254 patients. Cyclophosphamide was served as the control drug in all trials. The SLEDAI score, urine protein level and serum creatinine decreased significantly following leflunomide treatment (P<0.05). Leflunomide was superior to cyclophosphamide in achieving complete and total remission, but no difference in SLEDAI score was found between these two treatments (P>0.05). Additionally, patients receiving leflunomide treatment showed favorable renal function profiles, especially regarding the 24-hour proteinuria (mean difference: -0.58, 95%CI: -0.78~-0.37, P<0.01) and serum creatinine (mean difference: -0.20, 95%CI: -0.39~-0.01, P<0.05). In the safety comparison, leflunomide was safer than cyclophosphamide regarding adverse drug reactions (ADRs), including liver damage (RR = 0.53, 95%CI: 0.33~0.87, P<0.05), alopecia (RR = 0.38, 95%CI: 0.17~0.85, P<0.05), leukopenia (RR = 0.25, 95%CI: 0.08~0.77, P<0.05) and infection (RR = 0.54, 95%CI: 0.32~0.92, P<0.05), without increased risk of gastrointestinal reaction, rash or herpes zoster infection.
CONCLUSIONS
Leflunomide is a promising therapy for LN treatment, primarily because of the comparable efficacy and favorable safety profile determined by this meta-analysis of RCTs. Larger RCTs with longer duration of observation are necessary to provide strong evidence of the efficacy and safety of leflunomide in LN patients.
Topics: Adult; Asian People; Cyclophosphamide; Female; Humans; Isoxazoles; Leflunomide; Lupus Nephritis; Male; Odds Ratio; Remission Induction; Treatment Outcome
PubMed: 26670616
DOI: 10.1371/journal.pone.0144548 -
The Cochrane Database of Systematic... Sep 2015Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions comprises steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This an update of a review first published in 2008.
OBJECTIVES
To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register up to 27 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes.
MAIN RESULTS
Thirty one studies (2217 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large transnational study groups.Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at three months (2 studies: RR 0.43, 95% CI 0.23 to 0.78) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72). Four studies (300 patients) compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leucopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in granulomatosis with polyangiitis.
AUTHORS' CONCLUSIONS
Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil were also effective. Azathioprine, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
Topics: Acute Kidney Injury; Adult; Azathioprine; Cyclophosphamide; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Failure, Chronic; Plasma Exchange; Randomized Controlled Trials as Topic; Vasculitis
PubMed: 26400765
DOI: 10.1002/14651858.CD003232.pub3 -
The Journal of Rheumatology Oct 2016To compare benefits and harms of lupus nephritis (LN) induction and maintenance treatments. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare benefits and harms of lupus nephritis (LN) induction and maintenance treatments.
METHODS
We performed a systematic review and Bayesian network metaanalyses of randomized controlled trials (RCT) of immunosuppressive drugs or corticosteroids (CS) in LN. OR and 95% credible intervals (CrI) were calculated.
RESULTS
There were 65 RCT that met inclusion and exclusion criteria. Significantly lower risk of endstage renal disease (ESRD; 17 studies) was seen with cyclophosphamide (CYC; OR 0.49, 95% CrI 0.25-0.92) or CYC + azathioprine (AZA; OR 0.18, 95% CrI 0.05-0.57) compared with standard-dose CS, and with high-dose (HD) CYC (OR 0.16, 95% CrI 0.03-0.61) or CYC + AZA (OR 0.10, 95% CrI 0.03-0.34) compared with HD CS. HD CS was associated with higher risk of ESRD compared with CYC (OR 3.59, 95% CrI 1.30-9.86), AZA (OR 2.93, 95% CrI 1.08-8.10), or mycophenolate mofetil (MMF; OR 7.05, 95% CrI 1.66-31.91). Compared with CS, a significantly higher proportion of patients had renal response (14 studies) when treated with CYC (OR 1.98, 95% CrI 1.13-3.52), MMF (OR 2.42, 95% CrI 1.27-4.74), or tacrolimus (TAC; OR 4.20, 95% CrI 1.29-13.68). No differences were noted for the risk of malignancy (15 studies). The risk of herpes zoster (17 studies) was as follows: OR (95% CrI) MMF versus CS 4.38 (1.02-23.87), CYC versus CS 6.64 (1.97-25.71), TAC versus CS 9.11 (1.13-70.99), and CYC + AZA versus CS 8.46 (1.99-43.61).
CONCLUSION
Renal benefits and the risk of herpes zoster were higher for immunosuppressive drugs versus CS. Data on relative and absolute differences are now available, which can be incorporated into patient-physician discussions related to systemic lupus erythematosus medication use.
Topics: Adrenal Cortex Hormones; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Remission Induction; Tacrolimus; Treatment Outcome
PubMed: 27585688
DOI: 10.3899/jrheum.160041 -
Clinical Advances in Hematology &... Oct 2022Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal... (Review)
Review
BACKGROUND
Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal approach to AL-CA.
OBJECTIVE
We conducted this systematic review to summarize current evidence from published studies about the safety and efficacy of various treatment regimens for patients with AL-CA, mainly focusing on autologous stem cell transplant (ASCT) and heart transplant.
METHODS
An electronic literature search of PubMed, Web of Science, Scopus, EBSCO, and CINAHL Plus was conducted through December 2019 using the relevant keywords and prespecified MeSH terminology. Records were screened, and eligible studies were selected and narratively discussed. Data on the hematologic and cardiac responses as well as the safety of the treatment regimens were extracted and synthesized narratively in the context of the systematic review.
RESULTS
Thirty published articles were included in this systematic review. The most commonly used first-line treatment in the included studies was bortezomib-based therapy followed by high-dose melphalan and ASCT, with recent evidence of improved outcome with the addition of daratumumab. Heart transplant was found to extend survival for selected patients who were not eligible for ASCT; however, it was found to affect the patients' tolerance of further chemotherapy in some studies. Published data on longterm outcomes with immunomodulatory agents were scarce.
CONCLUSION
Current evidence suggests several possible regimens for the treatment of AL-CA. Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations in moderate/severe forms of cardiac involvement, followed by high-dose melphalan and ASCT in eligible patients, and heart transplant for selected severe cases. Therefore, we highlight the necessity of conducting well-designed, randomized controlled trials to provide evidence about the efficacy of these drugs with respect to ASCT.
Topics: Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Transplantation, Autologous; Treatment Outcome
PubMed: 36206073
DOI: No ID Found -
Advances in Therapy Jan 2017The Hepatic CHEMOSAT Delivery System is an innovative medical device for the treatment of patients with unresectable primary liver tumors or unresectable hepatic... (Review)
Review
UNLABELLED
The Hepatic CHEMOSAT Delivery System is an innovative medical device for the treatment of patients with unresectable primary liver tumors or unresectable hepatic metastases from solid organ malignancies. This system is used to perform chemosaturation percutaneous hepatic perfusion (CS-PHP), a procedure in which a high dose of the chemotherapeutic agent melphalan is delivered directly to the liver while limiting systemic exposure. In a clinical trial program, CS-PHP with melphalan significantly improved hepatic progression-free survival in patients with unresectable hepatic metastases from ocular or cutaneous melanoma. Clinically meaningful hepatic responses were also observed in patients with hepatocellular carcinoma or neuroendocrine tumors. Furthermore, the results of published studies and case reports demonstrated that CS-PHP with melphalan resulted in favorable tumor response rates in a range of tumor histologies (ocular or cutaneous melanoma, colorectal cancer, and hepatobiliary tumors). Analyses of the safety profile of CS-PHP revealed that the most common adverse effects were hematologic events (thrombocytopenia, anemia, and neutropenia), which were clinically manageable. Taken together, these findings indicate that CS-PHP is a promising locoregional therapy for patients with primary and secondary liver tumors and has a acceptable safety profile.
FUNDING
Delcath Systems Inc., New York, NY, USA.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Female; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 27798773
DOI: 10.1007/s12325-016-0424-4 -
Clinical and Experimental Rheumatology May 2022Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up... (Review)
Review
OBJECTIVES
Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up to two-thirds of RP patients. Necrotising scleritis (NS) and peripheral ulcerative keratitis (PUK) may be inaugural and may lead to eye perforation and vision loss. We aimed to review NS and PUK in RP, in order to characterise them, to identify successful treatment options and unmet needs.
METHODS
A systematic review of the currently available evidence in PubMed, EMBASE and Scopus was performed according to PRISMA, including observational studies, single case reports and case series of NS/PUK in RP. Study design, number of patients, age, gender, treatment and outcome, were extracted. Two RP patients also provided their opinion.
RESULTS
Five case reports and two case series were eligible for inclusion. We identified 10 RP patients with eye-threatening complications (NS and/or PUK), 9 adults (2 males, 7 females, aged 35-72, median age 57.6 years) and one paediatric patient (F, 11 years). Apart from glucocorticoids, cyclophosphamide was effective in 4 patients; infliximab, high-dose immunoglobulins, dapsone, or cyclosporine were also successfully employed in a case each. Surgical repair was reported in 2 cases.
CONCLUSIONS
Ocular inflammation is often bilateral and recurring in RP; NS/PUK are rare complications. All patients who develop NS/PUK should be specifically questioned for RP signs and symptoms. Early institution of immunosuppressive therapies is mandatory. Increasing awareness, physicians' and patients' education and a multidisciplinary approach may help improve the prognosis of these serious complications of RP.
Topics: Adult; Child; Corneal Ulcer; Cyclophosphamide; Female; Humans; Infliximab; Male; Middle Aged; Polychondritis, Relapsing; Scleritis
PubMed: 35238768
DOI: 10.55563/clinexprheumatol/27n7im