Latest news with #cyclophosphamide
Medscape
29-07-2025
- Health
- Medscape
Rituximab No Better Than Standard Therapy for EGPA Remission
TOPLINE: Rituximab did not show superiority over conventional therapy in inducing remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Both treatment groups had similar remission rates at 180 and 360 days, with no significant differences in relapse rates or adverse events. METHODOLOGY: A phase 3, multicenter, randomized, controlled superiority trial was conducted in France to compare rituximab with conventional therapy for EGPA remission induction. A total of 105 adult patients with active EGPA (mean age, 58.4 years; 52.4% women), defined by a Birmingham Vasculitis Activity Score (BVAS, version 3) ≥ 3, were enrolled between December 2016 and October 2019 and randomly assigned to receive either rituximab (n = 52) or conventional therapy on the basis of the five-factor score (n = 53). Patients in the rituximab group received 1 g of rituximab on days 1 and 15, along with glucocorticoids on a tapering schedule; those with a five-factor score ≥ 1 received placebo-cyclophosphamide and placebo-uromitexan. The conventional therapy group received glucocorticoids on a tapering schedule with or without cyclophosphamide on the basis of a five-factor score ≥ 1. The primary endpoint was the proportion of patients who achieved remission, defined as the absence of EGPA disease activity (indicated by a BVAS of 0 at a prednisone dose of ≤ 7.5 mg/d), at 180 days. Secondary endpoints included the duration of remission, glucocorticoid dose, and safety, with follow-up visits scheduled up to 360 days. TAKEAWAY: At 180 days, 63.5% of patients in the rituximab group and 60.4% in the conventional group achieved remission (relative risk, 1.05; P = .75). At 360 days, remission rates were similar between the groups: 59.6% in the rituximab group and 64.2% in the conventional group. The time to remission was a median of 2 weeks in both the groups. Among patients who achieved a BVAS of 0, the mean duration of remission was comparable — 48.5 weeks for rituximab and 49.1 weeks for conventional therapy. No significant differences were observed in relapse rates or serious adverse event rates between the rituximab and conventional therapy groups. Infections and cardiovascular events were the most common serious adverse events. IN PRACTICE: 'On the basis of the results of this trial, the role of rituximab in the therapeutic management of EGPA has been updated,' the authors of the study wrote. 'In most of the study population with nonsevere EGPA, the lack of a clinically meaningful effect of rituximab in addition to the conventional strategy of glucocorticoids alone may appropriately inform clinical decision-making,' they added. SOURCE: The study was led by Benjamin Terrier, MD, PhD, Université Paris Cité in Paris, France. It was published online on July 28, 2025, in Annals of Internal Medicine. LIMITATIONS: The study's design as a superiority trial may not adequately address the equivalence between rituximab and conventional therapy. The limited sample size, due to the rarity of EGPA, affected the precision of subgroup analyses. The focus on remission induction in the vasculitis phase may differ from other studies. DISCLOSURES: The study was funded by research grants from the French Ministry of Health and sponsored by Assistance Publique-Hôpitaux de Paris. Additional disclosures are noted in the original article online. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
02-07-2025
- Health
- Medscape
Predictors and Therapies in Primary CNS Angiitis Outcomes
TOPLINE: Long-term outcomes in primary angiitis of the central nervous system (PACNS) were influenced by patient/disease factors; compared with no treatment, treatment with cyclophosphamide (alone or with steroids) was associated with a reduction in relapse rates. METHODOLOGY: This retrospective observational cohort study included 163 adults (median age, 48 years; 45% women) diagnosed with PACNS at 13 German tertiary care centres from 2004 to 2018. Patients met Calabrese and Mallek (1988) and Birnbaum and Hellmann (2009) diagnostic criteria and were classified as biopsy- and angiogram-confirmed. Researchers assessed the risk for relapse across six immunotherapy regimens (no treatment, steroids, cyclophosphamide ± steroids, and others). Outcomes — survival, relapse-free survival (median follow-up, 42 months), and disability (measured using the modified Rankin scale) — were assessed through telephone interviews/registry data. TAKEAWAY: Overall, 18% of patients with PACNS died during follow-up, with each 10-year increase in age significantly increasing the risk for mortality (hazard ratio [HR], 1.96; 95% CI, 1.41-2.74; P < .001). Over half of patients (52%) developed moderate-to-severe disability, defined as a modified Rankin scale score of 3-6, that was strongly associated with older age (odds ratio, 1.40 per 10 years). Relapses occurred in 50% of patients, typically occurring at a median of 18 months (interquartile range, 4-55 months), indicating a high rate of PACNS recurrence over time. Cyclophosphamide monotherapy (HR, 0.44) and steroid combinations (HR, 0.47) significantly lower the risk for relapse than no treatment. IN PRACTICE: "Our findings further support the treatment of patients with PACNS with cyclophosphamide alone or in combination with steroids to reduce the frequency of relapse," the authors wrote. SOURCE: This study, led by Anna Lena Fisse, Department of Neurology, Ruhr University Bochum, St. Josef Hospital, Bochum, Germany, was published online on June 23, 2025, in Annals of Neurology. LIMITATIONS: The non-randomised observational design introduced potential confounding as treatment intensity correlated with disease severity. Variable follow-up durations and non-treatment in some cases could bias outcome interpretation. DISCLOSURES: This study reported open access funding enabled and organised by Projekt DEAL. Some authors reported receiving speaking fees, honoraria, travel support, and research funding; serving as paid consultants; and having other financial ties with several pharmaceutical companies. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Yahoo
15-05-2025
- Business
- Yahoo
Nkarta Downgraded, Analyst Cites Competitive Pressure In Autoimmune Space
Nkarta Inc. (NASDAQ:NKTX) on Wednesday reported a first-quarter loss of 43 cents per share, beating the consensus loss of 44 cents. As of March 31, 2025, Nkarta had $351.9 million in cash, cash equivalents, restricted cash, and investments in marketable securities. The company expects its current cash and cash equivalents to be sufficient to fund its current operating plan into the clinical development of NKX019 for autoimmune diseases, the Ntrust-1 trial of NKX019 for lupus nephritis (LN) expanded to include patients with primary membranous nephropathy (pMN). Ntrust-1 is currently open to enrolling patients with pMN and remains open to enrolling patients with LN. The Ntrust-2 trial of NKX019 for systemic sclerosis, idiopathic inflammatory myopathy, and anti-neutrophil cytoplasmic antibody-associated vasculitis continues to enroll patients. Ntrust-1 and Ntrust-2 protocols were amended to modify lymphodepletion before administration of NKX019 to use a combination of fludarabine and cyclophosphamide, with the option for eligible patients to continue to receive cyclophosphamide alone as modified lymphodepletion. The investigator-sponsored trial (IST) of NKX019 for myasthenia gravis, led by researchers at the University of California, Irvine, has opened for enrollment. The IST of NKX019 for systemic lupus erythematosus, led by researchers at Columbia University Irving Medical Center, remains open for enrollment. Preliminary clinical data from the Ntrust-1 and Ntrust-2 clinical trials are planned for the second half of 2025. Analyst at William Blair said, 'We view the expansion into pMN positively as it is the first cell therapy trial targeting pMN, to our knowledge, suggesting there will be minimal competition for patient enrollment compared to other indications like lupus nephritis.' Analyst Sami Corwin is concerned about the changes to the protocol that added Flu to the preconditioning treatment. It's unclear whether this decision was partly based on early trial data. 'Without using a reduced lymphodepletion regimen, it's becoming harder to see how NKX019 stands out from other CD19 allogeneic cell therapies in the crowded autoimmune disease market,' adds Corwin. 'In addition, while we look forward to the initial clinical data from the Ntrust-1 and Ntrust-2 trials in the second half of 2025, it is unclear if enough data will be shared for the data to be meaningful catalysts, and we think investors will have to wait until 2026 to get a more robust dataset,' the analyst says. William Blair has downgraded Nkarta from Outperform to Market Perform and writes that the allogeneic approach is favorable for autoimmune disease. However, it is unclear how differentiated the CAR-NK approach is compared to other allogeneic CAR therapies in the space. The analyst has increased the full-year 2025 net loss estimate to $144.7 million, or $1.95 per share. William Blair acknowledges the potential of Nkarta's pMN expansion but has become more cautious due to concerns about the modified lymphodepletion protocol and the resulting uncertainty about NKX019's differentiation in a competitive autoimmune market. They believe the current valuation reflects the risks and development stage. Price Action: NKTX stock is trading lower by 8.02% to $1.72 at the last check on Thursday. Image via Shutterstock Date Firm Action From To Mar 2022 Raymond James Initiates Coverage On Outperform Mar 2022 HC Wainwright & Co. Initiates Coverage On Buy Jan 2022 William Blair Initiates Coverage On Outperform View More Analyst Ratings for NKTX View the Latest Analyst Ratings UNLOCKED: 5 NEW TRADES EVERY WEEK. Click now to get top trade ideas daily, plus unlimited access to cutting-edge tools and strategies to gain an edge in the markets. Get the latest stock analysis from Benzinga? This article Nkarta Downgraded, Analyst Cites Competitive Pressure In Autoimmune Space originally appeared on © 2025 Benzinga does not provide investment advice. All rights reserved. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Medscape
12-05-2025
- Health
- Medscape
Prophylaxis in Vasculitis Cuts Risk for Non-PJP Infections
Prophylactic treatment with trimethoprim-sulfamethoxazole (TMP-SMX) significantly reduced the risk for serious infections by approximately 50% in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, with the greatest benefits observed during the first 180 days of treatment. METHODOLOGY: Researchers conducted an observational study that used a target trial emulation framework to examine the effect of prophylactic TMP-SMX on the incidence of serious infections in patients with ANCA-associated vasculitis. They included 296 patients with new-onset or relapsing ANCA-associated vasculitis from four tertiary referral hospitals in South Korea who received either rituximab or cyclophosphamide as induction therapy between 2005 and 2023. Of these, 240 patients received TMP-SMX prophylaxis (prophylaxis group; mean age, 63.7 years; 55.8% women) within 14 days of induction therapy, and 56 patients did not receive prophylaxis (control group; mean age, 61.5 years; 60.7% women) during the same period. Physicians at each institution determined patient eligibility for prophylactic TMP-SMX, with dosage being either one single-strength tablet (TMP 80 mg and SMX 400 mg) daily or one double-strength tablet (TMP 160 mg and SMX 800 mg) every other day, adjusted for renal function. The primary outcome was the incidence of serious infections requiring intravenous antimicrobial treatment, hospitalization, or extended hospital stay. Secondary outcomes included infection-related deaths and severe adverse drug reactions related to TMP-SMX. TAKEAWAY: Approximately 45.8% of patients discontinued the use of prophylactic TMP-SMX within the first 180 days. During 252.1 person-years of observation, 77 serious infections occurred in 65 patients, with an incidence rate of 30.5 per 100 person-years and a fatality rate of 18.5%. Most serious infections (85.7%) occurred within the first 180 days of observation (incidence rate ratio, 5.43; 95% CI, 2.87-10.28). The prophylaxis group had a significantly lower 1-year incidence than the control group (hazard ratio [HR], 0.48; 95% CI, 0.32-0.72), particularly during the first 180 days (HR, 0.41; 95% CI, 0.22-0.76) but not thereafter (HR, 3.76; 95% CI, 0.46-29.43). Infection-related mortality was also significantly lower in the prophylaxis group than in the control group (HR, 0.23; 95% CI, 0.10-0.53). Over 127.4 person-years of TMP-SMX prophylaxis, 35 cases of adverse events occurred, eight of which were adverse drug reactions related to prophylactic TMP-SMX, and 27 patients discontinued TMP-SMX. Only one case of severe adverse drug reaction was noted, which was resolved after treatment discontinuation. IN PRACTICE: 'Our results strongly suggest that prophylactic TMP-SMX provides additional benefits in patients with AAV [ANCA-associated vasculitis] beyond reducing the risk of PJP [ Pneumocystis jirovecii pneumonia],' the authors wrote. SOURCE: This study was led by Yun Kyu Kim, MD, Seoul National University College of Medicine, Seoul, Republic of Korea, and was published online on April 14, 2025, in Arthritis & Rheumatology . LIMITATIONS: Unmeasured confounders, such as compliance with prophylactic TMP-SMX, may have influenced the findings. The varied duration of TMP-SMX use in the prophylaxis group, with many patients discontinuing within 180 days, may have led to biased estimates. Additionally, the impact of TMP-SMX on COVID-19 incidence and related infectious complications could not be estimated for patients with an index date prior to 2018. DISCLOSURES: This study was supported by a grant from the National Research Foundation of Korea. One author reported receiving salary from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two authors reported receiving grants and consulting fees from various pharmaceutical companies.
