1.
Efficacy of plasma exchange for antineutrophil cytoplasmic antibody-associated systemic vasculitis: a systematic review and meta-analysis
Yamada Y, Harada M, Hara Y, Iwabuchi R, Hashimoto K, Yamamoto S, Kamijo Y
Arthritis research & therapy. 2021;23(1):28
Abstract
OBJECTIVE To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. METHODS A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. Randomised controlled trials (RCTs) comparing PE vs. non-PE in AAV patients (microscopic polyangiitis [MPA], granulomatosis with polyangiitis [GPA], or eosinophilic granulomatosis with polyangiitis [EGPA]) were included. The combined risk ratio (RR) was calculated by the random-effects model using the Mantel-Haenszel method. Heterogeneity was measured using the I(2) statistic. Primary outcomes were mortality, clinical remission (CR), and adverse events (AEs). RESULTS Four RCTs comparing PE vs. no PE (N = 827) and 1 RCT comparing PE vs. pulse steroid treatment (N = 137) were included. All participants were MPA or GPA patients (no EGPA patients). PE was not associated with main primary outcomes compared with no PE (mortality RR 0.93 [95% confidence interval {CI} 0.70-1.24], I(2) = 0%; CR RR 1.02 [95% CI 0.91-1.15], I(2) = 0%; and AE RR 1.10 [95% CI 0.73-1.68], I(2) = 37%) or pulse steroid (mortality RR 0.99 [95% CI 0.71-1.37]; CR [the Birmingham Vasculitis Activity score] mean difference - 0.53 [95% CI - 1.40-0.34]; and AE RR 1.05 [95% CI 0.74-1.48]). Focusing on the early treatment phases, PE was associated with a reduction in end-stage renal disease incidence compared with both no PE (PE 1/43 vs. no PE 10/41; RR 0.14 [0.03-0.77] at 3 months) and pulse steroid (PE 11/70 vs. pulse steroid 23/67; RR 0.46 [0.24-0.86] at 3 months). CONCLUSION We carried out a systematic review and meta-analysis targeting all AAV patients, including MPA, GPA, and EGPA. In AAV patients, performing PE was not associated with the risk of mortality, CR, and AE. No RCT exists evaluating the efficacy of PE for EGPA; hence, this is required in the future. The results may affect the development of guidelines for AAV and may indicate the direction of future clinical research on AAV. TRIAL REGISTRATION UMIN R000045239 , PROSPERO CRD42020182566 .
2.
Randomized phase 2 dose-finding study of weekly administration of darbepoetin alpha in anemic patients with lung or ovarian cancer receiving multicycle platinum-containing chemotherapy
Ichinose Y, Seto T, Nishiwaki Y, Ohe Y, Yamada Y, Takeda K, Saijo N, Hotta T
Japanese Journal of Clinical Oncology. 2010;40((6):):521-9.
Abstract
OBJECTIVE This is the first clinical trial for Japanese to evaluate the dose-response and determine the clinically effective dose of darbepoetin alpha by weekly subcutaneously administration in anemic patients with lung cancer or ovarian cancer receiving chemotherapy. METHODS Eligible patients were required to have anemia (hemoglobin level of 15. 0 g/dl (for men) or 14. 0 g/dl (for women), and reinstated at 50% of the previous weekly dose when the hemoglobin level decreased to RESULTS Hemoglobin response rate was 31. 6%, 55. 6% and 70. 3% in 1. 0, 2. 25 and 4. 5 microg/kg groups, respectively. The dosages of 2. 25 and 4. 5 microg/kg thus met the clinically effective dose criterion of at least 50% of patients achieving a hemoglobin response. The FACT-fatigue subscale had a high internal consistency with Cronbach's alpha score. Although no improvement in FACT-fatigue subscale score from baseline to the end of the treatment phase was confirmed for any dose group, there was a correlation between FACT-fatigue subscale score and hemoglobin concentration. Darbepoetin alpha appears to be well tolerated in this setting and no dose-dependent adverse events were observed. CONCLUSIONS Darbepoetin alpha alleviated anemia caused by platinum-based chemotherapy, and the dosage of 2. 25 microg/kg was the lowest dose that met the clinically effective dose criteria when administered once weekly.