Increased rates of APOs are associated with rheumatic diseases like SLE, rheumatoid arthritis (RA), and dermatomyositis, but little is known about pregnancy outcomes among patients with ASDs. Therefore, researchers conducted a case-control study to assess the frequency of APOs among women with ASDs.

Data were taken from the TriNetX United States Collaborative Network database and included patients aged between 15 to 44 years who were pregnant, from January 1, 2016, to December 31, 2021.

Patients with ASDs were propensity score matched 1:1 with members of two control groups for comparison: 1) healthy patients without ASDs, RA, or SLE and 2) individuals with RA or SLE who were considered members of the disease-control group.

The study included 3654 patients with ASDs and 3654 members of the control groups (2147 patients with SLE and 889 with RA).

Patients with ASDs were at greater risk of experiencing spontaneous abortion and preeclampsia/eclampsia compared with members of the healthy control group.

Specifically, the risk for spontaneous abortion was 1.5 times higher among patients with ASDs than in the healthy control group (P <.001), while the risk for preeclampsia/eclampsia was 1.2 times higher among patients with ASDs compared with the healthy control group (P =.04).

Compared against women with SLE, women with ASDs were less likely to experience preeclampsia/eclampsia, have a preterm birth, experience preterm premature rupture of membranes (PPROM), or have a fetus with intrauterine growth restriction (IUGR).

Specifically, the risk for preeclampsia/eclampsia was 0.7 times lower (P =.001), the risk of delivering preterm was 0.5 times lower (P <.001), the risk for PPROM was 0.6 times lower (P =.004), and the risk of having a fetus with IUGR was 0.6 times lower (P <.001) among women with ASDs vs women with SLE.

Women with ASDs were more 1.2 times more likely to experience a spontaneous abortion than women with SLE (P =.003). Patients with ASDs and RA were at similar risk for APOs.

The study authors concluded, “These results suggest that patients with ASDs have increased rates of adverse pregnancy outcomes compared to healthy controls and are similar in risk to RA. In contrast, those with SLE have a greater frequency of APOs indicating that all these groups may benefit from multidisciplinary care with maternal-fetal medicine specialists.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor. The application is supported by data from the phase 2 AGAVE-201 study (ClinicalTrials.gov Identifier: NCT04710576), which evaluated the safety and efficacy of axatilimab in 241 adult and pediatric patients with recurrent or refractory active GVHD whose disease had progressed after 2 therapies. Prior treatments included ruxolitinib (74%), ibrutinib (31%) and belumosudil (23%).

Study participants were randomly assigned to 1 of 3 treatment groups: 0.3mg/kg every 2 weeks, 1mg/kg every 2 weeks, or 3mg/kg every 4 weeks. The primary endpoint was overall response rate (ORR) defined as the proportion of patients in each dose group who achieved an objective response based on 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1.

Findings showed patients receiving 0.3mg/kg every 2 weeks had the highest ORR, 74% (95% CI, 63-83), within the first 6 months of treatment. Median time to response in this cohort was 1.7 months (range, 0.9-8.1); 60% of these patients maintained a response at 12 months. 

In the 0.3mg/kg dose group, 55% of patients achieved at least a 7-point improvement in the modified Lee Symptom Scale score (secondary endpoint). Additionally, organ specific responses were observed across all organs involved at baseline, with notable responses in fibrosis-dominated organs: esophagus (78%), joints and fascia (76%), lungs (47%), and skin (27%).

The most common treatment-emergent adverse events reported were increases in aspartate aminotransferase, blood creatine phosphokinase, lipase, lactate dehydrogenase, and alanine aminotransferase.

“Despite recent advancements in the treatment of patients with chronic GVHD, there remains a significant unmet need for patients who progressed on earlier lines of therapy,” said Hervé Hoppenot, CEO , Incyte. “Axatilimab’s novel mechanism offers a differentiated treatment approach which may help patients suffering from this devastating disease. We look forward to working closely with the FDA and our partners at Syndax on the review of our application for axatilimab for this indication.”

A Prescription Drug User Fee Act date of August 28, 2024 has been set for the application.

Fabian Müller, MD, from the Friedrich-Alexander University Erlangen-Nürnberg in Germany, and colleagues examined patients with severe systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, or systemic sclerosis (8, 3, and 4 patients, respectively) who received a single infusion of CD19 CAR T-cells after fludarabine and cyclophosphamide preconditioning. Efficacy was assessed up to 2 years after CAR T-cell infusion, measured using the Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index.

Patients were followed for a median of 15 months. The mean duration of B-cell aplasia was 112 ± 47 days. The researchers found that all patients with SLE had DORIS remission, all patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and a reduction in the score on the EUSTAR activity index was seen for all patients with systemic sclerosis. In all patients, immunosuppressive therapy was completely stopped. In 10 patients, grade 1 cytokine release syndrome occurred.

“Even though it is premature to judge whether these patients are indeed cured from their autoimmune disease, CD19 CAR T-cells at least appear to be able to achieve sustained disease- and drug-free remission,” the authors write.

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The Food and Drug Administration (FDA) has granted Fast Track designation to CABA-201 for the treatment of systemic lupus erythematosus (SLE) and lupus nephritis.

CABA-201 is a 4-1BB-containing fully human CD19-chimeric antigen receptor (CAR) T cell investigational therapy. SLE is characterized by abnormal B cell function and autoantibody production. CABA-201 is a one-time infusion designed to deplete CD19-positive B cells, thereby improving disease activity in patients with SLE and lupus nephritis.

An open-label, phase 1/2 clinical trial has been cleared to begin and will include 6 patients with SLE with active lupus nephritis, as well as 6 SLE patients without renal involvement. Prior to infusion with CAB-201, study participants will be treated with a standard preconditioning regimen that includes fludarabine and cyclophosphamide.

“We believe the FDA’s decision to grant Fast Track designation for CABA-201 underscores the unmet need for a treatment that has the potential to provide deep and durable responses for people living with lupus and potentially other autoimmune diseases where B cells contribute to disease,” said David J. Chang, MD, Chief Medical Officer of Cabaletta. “We look forward to initiating the phase 1/2 trial for CABA-201 and further evaluating its therapeutic potential for patients in need.”

Treatment with anti-CD19 CAR T cell therapy led to remission in 5 patients with active SLE who where refractory to several immunosuppressive treatments, according to results from a small study. Findings also showed that the treatment was well tolerated; cytokine release syndrome was reported to be mild.

HealthDay News — Young patients with destructive nasal lesions commonly have current cocaine use, according to a study published online April 4 in Rheumatology Advances in Practice.

Charn Gill, from the University of Birmingham in the United Kingdom, and colleagues conducted a retrospective case series analysis of patients presenting with cocaine-induced midline destructive lesions or vasculitis compatible with granulomatosis with polyangiitis (GPA) between 2016 and 2021. A total of 42 patients (median age, 41 years) were identified with cocaine-induced midline lesions or systemic disease.

The researchers found that current cocaine use was common; when routine urine toxicology was performed, 20 of 23 samples provided were positive. Based on a urine toxicology analysis, 9 patients who denied ever using cocaine were identified as users and 11 tested positive despite stating that they were ex-users. High incidences of septal perforation and oronasal fistula were seen (75 and 15%, respectively). Systemic manifestations were seen in 27% of participants, and only one had acute kidney injury. Of the patients, 56% were PR3-ANCA positive and none tested positive for MPO-ANCA. Even when immunosuppression was administered, symptom remission required cocaine discontinuation.

“We now include urine samples for drugs of abuse in our initial investigations of patients with GPA and in those who appear not to be responding to treatment. Sadly, we have seen young people with life-changing disfigurement because of cocaine-induced granulomatosis with polyangiitis,” a coauthor said in a statement. “A better understanding of this condition prevents us from potentially harming patients further by administering inappropriate, potentially toxic, and futile treatment.”

Abstract/Full Text

Adding low-dose cyclosphosphamide to rituximab is safe and prolongs relapse-free survival in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, recent study findings suggest.

A team led by Pieter van Paassen, MD, PhD, of Maastricht University Medical Center, and colleagues compared the use of rituximab alone with rituximab plus cyclosphosphamide for inducing remission. The median follow-up was 48 months (minimum follow-up of 2 years). At baseline, renal involvement was more common in the combination therapy arm than in the monotherapy arm (85% vs 61%), the investigators reported in the Journal of Translational Autoimmunity.

Major relapse rates within 2 years, but not after 5 years, were significantly lower in the rituximab-cyclosphosphamide arm than in the rituximab-only group (3% vs 24%). At 2 and 5 years, the groups did not differ with respect to rates of infection, end-stage kidney disease, malignancies, hypogammaglobulinemia, and mortality.

“The results may support clinical decision making and contribute to future research,” the authors concluded. 

A major strength of the study is that it provides insight into treatment outcomes over a relatively long time period, with all patients followed up for at least 2 years, Dr van Paassen and colleagues noted. They also acknowledged study limitations, including a sample size that was “too small to create a prediction model and to identify possible risk factors for relapse and other adverse events.” Further, they pointed out that more patients in the combination arm than in the rituximab-only arm had renal involvement, “and clinicians tend to give [cyclosphosphamide] more frequently in patients with severe or rapidly progressive disease presentations.”

Reference

Ysermans R, Busch MH, Aendekerk JP, Damoiseaux JGMC, van Paassen P. Adding low dose cyclophosphamide to rituximab for remission-induction may prolong relapse-free survival in patients with ANCA vasculitis: A retrospective study. J Transl Autoimmun. 2022;6:100178. doi:10.1016/j.jtauto.2022.100178

Avacopan is safe and efficacious for patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) receiving background induction therapy with rituximab, investigators reported.

At 52 weeks, avacopan plus rituximab is associated with a higher remission rate and improved recovery of renal function compared with prednisone taper plus rituximab, according to findings from a subgroup analysis of 214 patients in the phase 3 ADVOCATE trial (NCT02994927).

“As a new therapeutic agent, avacopan may be considered as a standard therapy along with rituximab for treatment of ANCA-associated vasculitis to induce and sustain remission,” Duvuru Geetha, MD, of the Johns Hopkins School of Medicine in Baltimore, Maryland, and colleagues wrote in Annals of the Rheumatic Diseases.

Of these, 107 received avacopan plus rituximab and 107 received prednisone taper plus rituximab. Remission at week 26 and sustained remission at week 52 were achieved by 77.6% and 71.0% of patients in the avacopan group, respectively, compared with 75.7% and 56.1% of patients in the prednisone taper group, respectively, the investigators reported.

The relapse rate following remission at any time was 8.7% in the avacopan group compared with 20.2% in the prednisone taper group. The avacopan group had a significant 58% reduction relapse risk at any time following remission compared with the prednisone taper group.

The avacopan group also experienced faster recovery of renal function. At week 52, mean estimated glomerular filtration rate (eGFR; mL/min/1.73m²) increased by 5.8 from 50.8 at baseline in the avacopan group compared with2.8 from 46.8 at baseline in the prednisone taper group.

Serious adverse events occurred in 34.6% and 39.3% of the avacopan and prednisone taper groups, respectively. Avacopan therapy also was associated with more rapid reduction in albuminuria and less glucocorticoid toxicity.

“The results of this subgroup analysis suggest that avacopan with background induction therapy with [rituximab] showed comparable efficacy to a prednisone taper with background [rituximab] in achieving remission at week 26 and a higher rate of sustained remission at week 52,” the authors wrote.

Disclosure: This research was supported by ChemoCentryx (a wholly owned subsidiary of Amgen). Please see the original reference for a full list of disclosures.