THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Plenary III: Data shows belimumab improves SLE control, renal outcomes, steroid use

Richard Furie, MD
Richard Furie, MD

Adding belimumab to standard treatment improves overall systemic lupus erythematous (SLE) control, improves renal outcomes, and reduces overall steroid use compared to standard treatment alone. The BLISS-LN trial reinforces post hoc results from other belimumab trials showing improvement in renal parameters for patients with SLE.

“BLISS-LN met its primary and key secondary endpoints,” said Richard Furie, MD, chief of rheumatology, Northwell Health. “Importantly, the separation in results began about week 24 and continued through the end of the study at week 104.”

Dr. Furie was the first of six presenters for Plenary III at ACR Convergence 2020. Registered attendees have on-demand access to watch a replay of the session through Wednesday, March 11, 2021.

BLISS-LN compared outcomes for 446 patients with SLE on standard regimens of high-dose corticosteroids plus mycophenolate mofetil or high-dose corticosteroids plus cyclophosphamide followed by azathioprine with either belimumab or placebo. The primary endpoint was primary efficacy renal response (PERR). Key secondary endpoints included complete renal response (CRR), time to renal-related event or death, and ordinal renal response (ORR).

The belimumab arm showed an odds ratio of 1.6 for PERR, 1.7 for CRR, and 0.5 for time to rental-related death or event at week 104. Belimumab also had an odds ratio of 1.5 for prednisone doses of 5 mg/d or less and 1.6 for 7.5 mg/d or less.

“There were no outstanding safety issues and adverse events were evenly distributed across the groups,” Dr. Furie said.

Denosumab Superior to Alendronate for Lumbar Spine BMD in Long-Term Steroid Users

Chi Chiu Mok, M
Chi Chiu Mok, M

An investigator-initiated study found that denosumab (DEN) improves lumbar spine bone mineral density (BMD) more than alendronate (ALN) in patients with autoimmune inflammatory diseases on chronic glucocorticoids. 

“For patients who are not compliant or cannot tolerate oral bisphosphonates, I would consider switching to denosumab,” said Chi Chiu Mok, MD, chief of rheumatology, Tuen Mun Hospital, Hong Kong SAR, China.

Researchers compared BMD at the lumbar spine, total hip, and femoral neck in 139 patients on chronic corticosteroid use for any medical illness.

Patients were randomized to either subcutaneous denosumab every six months or oral alendronate weekly, plus calcium and vitamin D3. Underlying diseases included lupus (81%), rheumatoid arthritis (9.4%), myositis (4%), and ANCA-associated vasculitis/polymyalgia rheumatica.

Denosumab patients showed a significant increase in lumbar spine BMD compared to ALN (p=0.045) and significant decreases in bone turnover markers (p<0.001 for CTX, p=0.001 for P1NP). There were no new symptomatic fractures in the study and no significant differences in adverse events or steroid use between groups.

Type 1 IFN Induces Unique Cytotoxic CD8 T Cell Population in Checkpoint-Inhibitor Associated Arthritis

Runci Wang, MD, PhD
Runci Wang, MD, PhD

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by blocking PD-1, PD-L1, or CTLA-4 to stimulate anti-tumor response. About 5% of patients treated with CIs have a novel autoimmune side effect, checkpoint inhibitor-arthritis (CI-A).

CI-A can resemble rheumatoid arthritis or spondyloarthropathy, but the pathogenesis of CI-A is not known. New research found that synovial fluid from CI-A patients contains a unique population of cytotoxic CD38hi T cells with an increased interferon signature in both serum and synovial fluid.

This CD38hi T-cell population is not seen in synovial fluid from either RA or SpA patients, noted Runci Wang, MD, PhD, research fellow at Brigham and Women’s Hospital and Harvard Medical School. Nor do synovial fluid CD8 T cells from RA or SpA patients exhibit the interferon signature seen in CI-A serum and synovial fluid CD8 T cells.

“Type 1 interferon induces CD8 cells to acquire this new phenotype, which may be mediated by PD1 blockade,” Dr. Wang said.  “Interferon signaling has potential diagnostic and therapeutic application.”

Treat-to-Target Superior to Usual Care in Axial Spondyloarthritis

Anna Molto, MD
Anna Molto, MD

There are recommendations for a treat-to-target (T2T) strategy for axial spondyloarthritis, but little data exist about implantation or utility in daily practice. The international trial found that T2T is cost effective and numerically superior to usual care for axSpA, but differences in clinical outcomes are not statistically significant.

“There was a general trend, always in favor of T2T, over the efficacy outcomes compared to usual care,” said Anna Molto, MD, PhD, epidemiology and rheumatology researcher, Cochin Hospital, Paris, France. “And T2T is cost-effective at €20,000 per quality-adjusted life year (about $23,780). We have instituted T2T in our own practice.”

Ten centers in Belgium, France, and the Netherlands were randomized 1:1 to T2T or usual care, with 80 patients in each arm. In each arm, 72 patients completed the 12-month study.

Researchers compared usual care, with visits every 12 weeks, to T2T with visits every four weeks and strict adherence to therapeutic recommendations.

The primary endpoint was the percentage of patients with ASAS-HI improvement of 30%. Secondary endpoints included two dozen disease measures, patient-reported outcomes, functional and quality-of-life measures, treatment regimens, work impairment, safety, and cost-effectiveness analysis.

More T2T patients showed at least 30% ASAS-HI improvement than usual care, 45% vs. 36%, but the difference was not statistically significant. Most secondary outcomes also showed numerical, but not statistically significant, trends favoring T2T. And while significantly more biologics were used in the T2T arm, adverse events were similar in both groups.

Citrulline Reactive B Cells Found in Lungs of Individuals at Risk for RA and with Early Untreated RA

Vijay Jashua, PhD
Vijay Jashua, PhD

High-resolution computed tomography abnormalities are more common in RA patients who are positive for anti-citrullinated protein antibodies (ANCA+), and ectopic lymphoid structures harboring citrulline reactive cells are present in the lungs of RA patients. But little is known about the presence or role of citrulline reactive B-cells in the lungs of individuals at risk for RA or who have early stage, untreated disease.

Researchers compared bronchoalveolar lavage cells from patients at risk for RA, ACPA+ patients who have early RA, and ACPA- patients with early RA. They found a higher proportion of CD19+ B cells in ACPA+ individuals whether they had seropositive RA or were at risk for RA compared to ACPA- individuals. Lung ACPAs are similar to ACPAs from RA synovial B cells.

“This is the first time ACPA+ cells have been isolated in the lungs of individuals at risk for RA and with early RA,” said Vijay Joshua, PhD, postdoctoral researcher, Center for Molecular Medicine, Karolinska Institutet and University Hospital. “Lung monoclonal ACPAs react to different citrullinated antigens. Some of the lung ACPAs bind to activated neutrophils, some can promote migration of synovial fibroblasts challenged by starvation, and some can promote osteoclastogenesis.”  

ILD Not a Counterindication to Pregnancy

Aardra Rajendran, BSc
Aardra Rajendran, BSc

Women with interstitial lung disease (ILD) are often advised to avoid or terminate pregnancy because of pulmonary and circulatory changes often seen in ILD. Parenchymal fibrosis could prevent lung expansion and adequate oxygenation. And the typical 50% increase in maternal blood volume could lead to decompensation with rapid fluid shifts peri- and postpartum.

“We actually have very little data on adverse pregnancy outcomes in ILD,” said Aardra Rajendran, MD candidate, Duke University School of Medicine. “There are only four prior studies with small sample sizes.”

Rajendran analyzed Duke University Health System pregnancy outcomes in patients with ILD secondary to autoimmune disease from 1996 to 2019. She found 94 pregnancies and stratified them from normal pulmonary function tests (PFTs) though mild, moderate, and severe ILD, then compared adverse pregnancy outcomes (APOs) across the groups. 

A third of pregnancies (32%) had no PFTs, 10% had normal PFTs, 34 percent had mild ILD, 17% had moderate ILD, and 7% had severe ILD. Most patients, 69%, had sarcoidosis, 31% had connective tissue disease, and 83% were Black.

All of the women with severe ILD had an adverse pregnancy outcome (APO). Of women with moderate ILD, 42% had APOs, 29% for mild and 38% for normal PFTs. There were no maternal deaths.

“This largest-to-date cohort of pregnancies in ILD suggests that women with ILD may not need to avoid conception or terminate pregnancies,” Rajendran said. “But preconception counseling could be helpful, especially for women with more severe ILD. All of these women need a PFT and an echo cardiogram before conception or as early in pregnancy as possible and they need autoimmune medications compatible with pregnancy.”