ANCA-associated pulmonary-renal syndrome treated with cyclophosphamide, rituximab, repeated methyl-prednisolone pulses and a reduced oral glucocorticoid regime: an observational study.

OBJECTIVES: To describe the clinical outcome of patients with pulmonary-renal syndrome (PRS) due to ANCA-associated vasculitis (AAV) from a single centre. METHODS: Observational study of routine clinical care data of patients diagnosed with PRS due to AAV from 2010 to 2020 at the Autoimmune Diseases Unit, Hospital Universitario Cruces. Mortality due to any cause within 24 months was defined as the primary outcome. Secondary outcomes included end-stage kidney disease and the need for oxygen therapy at 24 months. RESULTS: Fourteen patients were identified with a mean age at diagnosis of 62.71 years. At diagnosis, the median serum creatinine was 2.46 mg/dl and the median Birmingham Vasculitis Activity Score (BVAS) was 24. All patients were treated with repeated methyl-prednisolone pulses, 13 patients received iv cyclophosphamide 500 mg every two weeks and 12 patients received rituximab. The mean (SD) initial dose of oral prednisone was 25 (7) mg/d. A rapid tapering of oral prednisone was achieved in all patients as per protocol, with a mean (SD) dose of 10.6 (1.9) mg/d received within the first three months. No cases of death, end-stage kidney disease or with need for long-term oxygen therapy were seen. Three patients suffered a relapse and five patients had major infections, none of them opportunistic. The median creatinine and BVAS at 24 months were 1.30 mg/dl and 0, respectively. CONCLUSIONS: Combination therapy with iv cyclophosphamide and rituximab, with repeated methyl-prednisolone pulses and a rapid prednisone taper, results in early disease control, with low mortality, chronic organ damage and infections.

Eurolupus cyclophosphamide plus repeated pulses of methyl-prednisolone for the induction therapy of class III, IV and V lupus nephritis.

OBJECTIVE: To study whether adding repeated 125 mg methyl-prednisolone pulses (MP) to Eurolupus fortnightly intravenous cyclophosphamide (CYC) improves remission of lupus nephritis (LN) compared with recommended schedules. METHODS: Observational comparative study of patients with biopsy-confirmed class III, IV or V LN: 30 in the mycophenolate (MMF) group, 25 in the CYC group and 38 in the CYC-MP group. The main efficacy outcome was complete response at 12 months. RESULTS: Patients in the CYC-MP group received lower doses of prednisone within 6 months (mean 8.5 mg/d, vs. 15 mg/d in the MMF group vs. 24 mg/d in the CYC group, respectively). The complete response rates at 12 months were: CYC-MP 86%; CYC 56%; MMF 47% (p = 0.002) at Pr/Cr <0.5; CYC-MP 86%; CYC 65%; MMF 63% (p = 0.07) at Pr/Cr ≤0.7. The cumulative 12-month response rates for the CYC-MP, CYC and MMF groups were, respectively, 0.90, 0.58 and 0.63 (p = 0.004). In the adjusted Cox model, patients receiving CYC-MP were more likely to achieve complete response at Pr/Cr <0.5 than those in the MMF (HR vs. CYC-MP 0.33, 95%CI 0.16-0.65) and the CYC groups (HR vs. CYC-MP 0.47, 95%CI 0.21-1.04). Glucocorticoid-related toxicity was seen in 2.6% of the CYC-MP group, 24% of the CYC group and 20% of the MMF group (p = 0.029). CONCLUSION: The addition MP of 125 mg to each fortnightly dose of 500 mg of CYC improves response rates and reduces the need for oral glucocorticoids in patients with class III, IV and V LN.

Toxicidad pulmonar por carmustina: un diagnóstico a considerar a pesar de la época de COVID / Carmustine Pulmonary Toxicity: A Diagnosis to Bear in Mind Even in Times of COVID

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Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data.

OBJECTIVE: To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Comparative observational study using data collected from routine care at Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain in patients with COVID-19 pneumonia. We compared patients who received week-2-MP (125-250 mg/d x3) with those who did not, with the end-points time to death and time to death or endotracheal intubation. RESULTS: We included 242 patients with COVID-19 pneumonia and elevated inflammatory markers at admission. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died and 31 (12.8%) suffered death or intubation. The adjusted HRs for death and death or intubation for patients in the week-2-MP group were 0.35 (95%CI 0.11 to 1.06, p = 0.064) and 0.33 (95%CI 0.13 to 0.84, p = 0.020), respectively. These differences were specifically seen in the subcohort of patients with a SpO2/FiO2 at day 7 lower than 353 (adjusted HR 0.31, 95% CI 0.08 to 1.12, p = 0.073 and HR 0.34, 95%CI 0.12 to 0.94, p = 0.038, respectively) but not in patients with higher SpO2/FiO2. Patients receiving out-of-week-2-MP, non-pulse glucocorticoids or no glucocorticoids had an increased adjusted risk for both outcomes compared with week-2-MP group: HR 5.04 (95% CI 0.91-27.86), HR 10.09 (95% CI 2.14-47.50), HR 4.14 (95% CI 0.81-21.23), respectively, for death; HR 7.38 (95% CI 1.86-29.29), HR 13.71 (95% CI 3.76-50.07), HR 3.58 (95% CI 0.89-14.32), respectively, for death or intubation. These differences were significant only in the subgroup with low SpO2/FiO2. CONCLUSIONS: Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point.