Two phase 3 trials found that risankizumab, an IL-23 inhibitor, can significantly improve the signs and symptoms of psoriatic arthritis (PsA) in adults who have inadequate response or intolerance to conventional DMARD and/or biologic therapy. Risankizumab is already approved for the treatment of moderate-to-severe plaque psoriasis in adults.
The KEEPsAKE 1 and 2 trials compared risankizumab to placebo in adults with active PsA and a history of inadequate response or intolerance to at least one DMARD and/or at least one biologic. Results were presented on Saturday, Nov. 6, during Plenary I, which can be viewed by registered attendees through March 11, 2022.
A total of 1,407 patients were randomized 1:1 to 150 mg subcutaneous risankizumab or placebo at weeks 0, 4, and 16. Approximately half the patients were female, with a mean age of 52 years and mean BMI of 31. Key assessments included ACR20/50/70 criteria, change in Health Assessment Questionnaire Disability Index from baseline, and other clinical and quality-of-life measures at week 24.
“These patients had PsA for a mean of just over seven years with a high disease activity burden and a high disability index,” said Andrew Ostor, MD, Associate Professor of Medicine at Monash University and Principal Investigator at Emeritus Research in Melbourne, Australia. “They showed significant improvement on all assessment measures at week 24. We saw similar rates of adverse events in the treatment and placebo groups with no new safety signals.”
Race, location key risk factors in lupus nephritis mortality
A new population-based study found that while lupus nephritis (LN) mortality declined from 1999 to 2015 in the U.S., there’s been an upward trend since. Non-white race and inner-city residence are independent risk factors for LN mortality, according to the study.
Researchers used the Centers for Disease Control and Prevention WONDER database to assess LN mortality based on ICD-10 codes for SLE and kidney diseases. Deaths were stratified by race/ethnicity and residence was stratified by urbanization data.
LN deaths declined 27% from 1999 to 2019, reported Ram Singh, MD, Professor of Medicine, Pathology and Laboratory Medicine at the University of California, Los Angeles, David Geffen School of Medicine, but mortality showed a steady increase from 2015 to 2019.
Compared to whites with LN, the relative risk of death was highest among non-Hispanic Blacks (4.5-fold), Hispanics (2.5-fold), and Asians/Pacific Islanders (1.5-fold). The risk of death from LN was highest in large, central metropolitan areas, followed by nonmetro areas, medium metro, small metro, and large metro fringe areas. The relative risk of death by location varied by race/ethnicity for all groups, though Blacks were more likely to die from LN regardless of location.
“Black, Hispanic, and Asian/Pacific Islander origins all carry an increased risk of mortality in lupus nephritis compared to white race,” Dr. Singh said. “Where you live can impact your health beyond individual race and ethnic factors.”
Abatacept may protect against progression from subclinical arthritis in high-risk patients
New data from the ARIAA study suggest that abatacept may block the progression of symptomatic arthritis to clinical disease.
In the double-blinded, placebo-controlled trial, 98 patients with symptomatic, subclinical arthritis were randomized to six months of abatacept or placebo plus 12 months of observation. Patients in the trial were anti-citrullinated protein antibodies (ACPA)-positive, had arthralgia for at least six weeks, and MRI inflammation in the dominant hand, but no past or present swelling and no glucocorticoid or DMARD treatment. The primary outcome was improvement in at least one MRI inflammation parameter by RAMRIS score; the secondary outcome was progression to arthritis by clinical joint swelling.
At six months, the abatacept group showed significant improvement in MRI inflammation (p=0.0043), fewer terminations (p=0.0032), and fewer progressions to arthritis (p=0.0025) versus placebo with no new safety signals from abatacept, reported Jürgen Rech, MD, from Friedrich-Alexander Universität in Erlangen-Nurnberg, Germany. Early analysis of 18-month data showed similar benefits from abatacept.
“We now know that the six months of treatment with abatacept will delay or prevent development of RA after 18 months in people at high risk for RA,” Dr. Rech said.
Blood-brain barrier leakage associated with cognitive impairment in SLE
New imaging data suggest that SLE patients with blood-brain barrier (BBB) leakage are more likely to have some degree of cognitive impairment (CI) than other SLE patients. The same study also found that nearly half of ambulatory SLE patients had some degree of CI, with visible differences in intra-network and inter-network brain connectivity in patients with and without CI.
CI is the most commonly reported manifestation of neuropsychiatric SLE, said John Hanly, MD, Professor of Medicine and Rheumatology at Queen Elizabeth II Health Sciences Center and Dalhousie University in Halifax, Canada. CI fluctuates in SLE, suggesting potential for reversal, he added.
Researchers used functional MRI neuroimaging to characterize brain function abnormalities in association with objectively defined CI, and diffusion contrast-enhanced MRI to assess BBB permeability in adults with SLE and healthy controls.
Dr. Hanly reported that 48% of SLE patients had a measurable degree of CI. Patients with SLE had fewer brain network connections than healthy adults, and SLE patients with CI had fewer brain network connections than non-CI patients. There was a strong association between extensive BBB leakage and increased CI, he said.
“These results suggest that blood-brain barrier permeability mediates cognitive impairment in SLE,” Dr. Hanley said. “It might be possible to target the blood-brain barrier in the future.”
Most immunosuppressants attenuate antibody titers following SARS-CoV-2 vaccination
New data from the COVaRiPAD study confirm early findings that methotrexate, corticosteroids, and other immunosuppressants commonly used to treat rheumatic disease can attenuate response to COVID-19 vaccination. Researchers also found that TNF inhibitors weaken mRNA vaccine response less than other agents tested.
COVaRiPAD is a prospective, observational study of COVID-19 vaccine responses in patients with autoimmune disease versus immunocompetent controls.
“The good news is that about 90% of patients mounted an antibody response,” reported Alfred Kim, MD, PhD, Assistant Professor of Medicine and of Pathology and Immunology at Washington University School of Medicine. “At the population level, antibody titers were reduced 3.4-fold compared to immunocompetent controls, but we saw vastly different responses to different drugs.”
Mycophenolate mofetil showed a 21-fold reduction in immunogenicity compared to a 9-fold reduction for glucocorticoids, 4.4-fold reduction for methotrexate, and a 3.5-fold reduction for azathioprine. Among DMARDs, B-cell depletion therapies showed a 57.5-fold reduction, followed by JAK inhibitors with a 2.6-fold reduction, and TNF inhibitors with a 2.3-fold reduction.
Peripheral blood B cells are key to vaccine response, particularly naïve B cells, Dr. Kim said. A six-month discontinuation of immunosuppression before vaccination could produce a stronger B-cell response and a more effective antibody response, he added.
REGISTER TODAY FOR ACR CONVERGENCE
If you haven’t registered for ACR Convergence 2021, register today to access all of the valuable content during the meeting, November 3–10. Registration also includes on-demand access to the virtual platform (session recordings, Poster Hall, Community Hubs, and ShowRheum) until March 11, 2022.