Only a fraction of the thousands of abstracts submitted for the ACR/ARP Annual Meeting are accepted. Five of the top abstracts will be presented during Plenary I on Sunday, starting with new data on cardiovascular risk in lupus patients.
Systemic lupus erythematosus (SLE) is recognized as an independent risk factor for premature cardiovascular disease, but not all patients are affected similarly, said Shivani Garg, MD, MS, Assistant Professor of Medicine, University of Wisconsin School of Medicine and Public Health. New data confirm that not only are African Americans with lupus at higher risk for cardiovascular complications compared to whites, but that elevated risk peaks in the first two years following diagnosis.
Researchers analyzed the Georgia Lupus Registry (GLR), a population-based registry from Atlanta, GA. All incident lupus patients from 2002-2004 were matched to the Georgia Hospital Discharge Database and the National Death Index from 2000-2013.
Cardiovascular events were 18-fold higher in African Americans compared to whites in the GLR during the initial ten years of follow up. African Americans also had cardiovascular events earlier than whites, peaking during the first two years following diagnosis. The findings suggest that cardiovascular prevention efforts should target African-American patients, particularly around the time of SLE diagnosis.
The session will take place from 11:00 am – 12:30 pm in Hall B1, Building B in the Georgia World Congress Center.
Rituximab superior to azathioprine for maintenance of remission in relapsing ANCA-associated vasculitis
Rituximab is licensed globally for induction of remission in ANCA-associated vasculitis. Neither of the trials leading to regulatory approvals of rituximab for the condition used maintenance treatment, and relapses were common.
“We started using maintenance rituximab for ANCA-associated vasculitis around 2006,” said Rona Smith, MD, Senior Research Associate at the University of Cambridge, UK. “We used two grams initially, then a gram every six months for two years. Relapse rates were considerably reduced with the repeat dosing. But historically, azathioprine has been a standard for relapsing disease. The RITAZAREM trial compared these approaches head-to-head.”
The global RITAZAREM trial randomized 170 patients with relapsing ANCA-associated vasculitis to rituximab or azathioprine as maintenance therapy after initial treatment with rituximab. Rituximab was superior to azathioprine in preventing disease relapse. Rituximab patients also experienced fewer major relapses, fewer severe adverse events, and fewer severe infections.
“We would like to see these findings reflected in clinical practice,” Dr. Smith said. “However, we recognize that rituximab is more expensive than azathioprine, which may affect how it is actually used in relapsing disease across the globe.”
Guselkumab safe, effective for active psoriatic arthritis
In the first phase 3 study of guselkumab in active psoriatic arthritis, the agent showed good efficacy for both joint and skin symptoms as well as physical functioning and quality of life compared to placebo with no new safety signals. The agent is already approved for plaque psoriasis.
“We already knew that guselkumab works nicely on the skin,” said Atul Deodhar, MD, Professor of Medicine and Medical Director, Rheumatology Clinics, Oregon Health & Science University. “Our primary endpoint was ACR20 at week 24.”
DISCOVER-1 randomized 381 patients with active PsA to guselkumab or placebo for the 24-week trial. Most were biologic-naïve, but about 30% had inadequate response to one or more TNF inhibitors. Guselkumab patients took either 100 mg every four weeks or 100 mg every eight weeks following a loading dose.
Most patients in the high dose group, 58.6%, had an ACR20 response at week 24. In the low dose group, 52.8% of patients had an ACR20 response at week 24. The placebo group showed a 22.2% ACR20 response. Guselkumab patients also showed higher ACR50, ACR70, PASI75/90/100, and MDA responses compared to placebo.
Long-term tocilizumab effective in giant cell arteritis
The initial phase of the GiACTA (Giant-Cell Arteritis Actemra) trial showed tocilizumab to be an effective 12-month treatment for giant cell arteritis (GCA). A two-year extension of GiACTA showed that many patients can discontinue tocilizumab after one year and maintain treatment-free remissions for at least two years.
Of the patients who received tocilizumab weekly during the original trial, 42% showed complete remission over the following 24 months, said John H. Stone, MD, MPH, Professor of Medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine and Director of Clinical Rheumatology at Massachusetts General Hospital Clinical.
Tocilizumab patients who experienced disease flares during the two-year follow-up were treated with tocilizumab, glucocorticoids or both, at the investigator’s discretion. Retreatment with tocilizumab was effective in restoring complete response.
“Giant cell arteritis requires ongoing management, but it does not necessarily require continuous treatment,” Dr. Stone said. “And patients who were randomized to tocilizumab used only about half the steroids compared to patients randomized to placebo over three years.
“Patients should be started on tocilizumab as soon as they are diagnosed,” he continued. “The goal should be to get them off steroids as quickly as possible and maintain their response with tocilizumab.”
Novel animal model for CTD-PAH
Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe complication of scleroderma and other autoimmune diseases. A familiar mouse model of arthritis may represent the first faithful animal model of CTD-PAH.
“One of the reasons we don’t have good treatment modalities for CTD-PAH is that we don’t have a good animal model,” said Benjamin Korman, MD, Assistant Professor of Allergy, Immunology and Rheumatology at the University of Rochester Medical Center. “Now that we have a mouse model that recapitulates nearly all of the key features of CTD-PAH, we have a tool to better understand pathogenesis and to evaluate potential treatments.”
Female human TNF-transgenic (TNF-Tg) mice die from cardiopulmonary disease by six months, he explained. Histologic analysis, immunofluorescent staining, CT angiography, and right heart catheterization confirmed that the mice show progressive pulmonary vasculopathy. Vasculopathy was reversed with anti-TNF therapy.
Progressive disease features include enlargement of pulmonary arteries, attenuation of distal arterioles, vascular occlusion, vascular collage deposition, and severely elevated right ventricular systolic pressures that closely resemble human CTD-PAH. Researchers also found elevated TNF-α expression in human CTD-PAH lung tissue, as well as strikingly similar genome-wide expression patterns between the lungs of TNF-Tg mice and CTD-PAH patients.
“This work provides pre-clinical rationale for a clinical trial to evaluate the effects of TNF inhibition in CTD-PAH patients,” Dr. Korman said. “It could be tricky to put such a trial together in this population, but that could be an exciting future direction.”