All groups showed improved mobility, pain, and function, but diet and exercise was superior in virtually all measures.
—Stephen P. Messier, PhD
“It’s quite remarkable that even if the patients had failed two or more TNF-inhibiting agents, they still had a significantly increased response to tofacitinib,” said Dr. Burmester, professor of medicine and director of rheumatology and clinical immunology at Charité-University Medicine Berlin. “This was a really sick patient population.”
About 35% of patients had used two or more TNF inhibitors without success, and 65% had inadequate response to one prior TNF inhibitor. Effects of tofacitinib were as rapid as typically seen with TNF inhibitors, said Dr. Burmester, who reports receiving research funding and consulting and speaking fees from the study sponsor, Pfizer.
One death due to pulmonary embolism occurred in the 10-mg tofacitinib group. Dr. Burmester said the cause possibly was concomitant postmenopausal hormone therapy.
The meeting’s basic science chair, Richard F. Loeser, Jr., MD, told The Rheumatologist that this study could change clinical practice.
“If we find out that tofacitinib is as effective as injections of TNF inhibitors, that will be a big breakthrough,” said Dr. Loeser, section head of molecular medicine at Wake Forest School of Medicine in Winston-Salem, N.C.
Cardiovascular Risk
In another RA study, Androniki Bili, MD, a rheumatologist at Geisinger Medical Center in Danville, Pa., reviewed electronic health records of an inception cohort of 1,829 patients with RA (abstract 719). She and her coworkers studied whether methotrexate and TNF-α inhibitors independently reduced the risk of cardiovascular disease (CVD)—a major cause of death in patients with RA—over a median follow-up of about three years. They classified patients as “ever users” or “never users” of methotrexate (n = 1,119 and 710, respectively) and TNF-α inhibitors (588 users versus 1,241 nonusers).
“Prior observational studies did not adjust for inflammatory burden, lipid profiles, or blood pressure,” Dr. Bili said; her study adjusted for these factors.
Prevalent CVD excluded 163 patients from the study. Use of methotrexate or TNF-α inhibitors, the researchers found, was independently associated with a reduction in incident CVD compared with patients who never used the medication. Patients receiving methotrexate therapy longer than 22 months had a 72% reduction in CVD, the authors calculate.
The CVD risk decreased further with prolonged drug exposure, according to Dr. Bili. The investigators reportedly observed a similar CVD reduction of 69% after more than 17 months of treatment with TNF-α inhibitors.
“Our results suggest these medications may be protective against cardiovascular disease in a group of patients who are at risk of cardiovascular disease,” she said.
However, observational studies cannot prove causation, Dr. Bili added. Given the homogeneous population (95% white, 73% female), she also cautioned against extrapolating the data to other populations.
Replying to a question from the audience, the presenter said they lacked sufficient power to break down results by specific TNF-α inhibitor.
Scleroderma
Most scleroderma experts agree that echocardiograms and pulmonary function tests should be performed annually in scleroderma patients to screen for pulmonary hypertension, said Ami A. Shah, MD, MHS, assistant professor of medicine at Johns Hopkins Scleroderma Center in Baltimore.
“However, prior data suggest that echocardiography screening is not used routinely in community rheumatology practices, even if patients are symptomatic with shortness of breath,” Dr. Shah said.
Prior data suggest that echocardiography screening is not used routinely in community rheumatology practices, even if [scleroderma] patients are symptomatic with shortness of breath.
—Ami A. Shah, MD, MHS
Prior study data suggest that right ventricular (RV) systolic pressure on an echocardiogram correlates only moderately with mean pulmonary artery pressure on right-sided heart catheterization.1 Because the value of echocardiography in screening for pulmonary hypertension is unclear, Dr. Shah and her colleagues performed a retrospective study of patients with scleroderma who had at least three echocardiograms in one year (abstract 720).
From data collected since 1990 at the researchers’ tertiary care center, 685 patients met inclusion criteria. The investigators compared the change in RV systolic pressure on 3,541 echocardiograms obtained at various clinical sites, and tracked patients’ deaths using the Social Security Death Index. Nearly 15% of patients had pulmonary arterial hypertension (PAH) confirmed by cardiac catheterization, the authors reported. Almost 27% of patients died over the eight-year mean follow-up (median survival was 11 years).
The researchers found that, when analyzing their entire scleroderma population, each 1-mm Hg increase in RV systolic pressure per year was strongly associated with an increased risk of PAH development and death (P<.0001 each).
“These data are supportive of the current recommendation for performing annual echocardiography in a scleroderma population,” Dr. Shah said. She added that a prospective study is needed to define the optimal screening strategy.
Knee Arthritis
The idea behind the IDEA, or Intensive Diet and Exercise for Arthritis, Trial was to determine if weight loss in older, overweight adults with painful knee osteoarthritis reduces pain and improves function and mobility (abstract 722). This international, prospective, single-blind, randomized controlled trial enrolled 454 patients aged 55 years or older who had a sedentary lifestyle and were overweight or obese.
According to lead author Stephen P. Messier, PhD, professor and director of the J. B. Snow Biomechanics Laboratory at Wake Forest University, patients were randomly assigned to one of three interventions for 18 months. Treatment arms were as follows:
- Diet only: An energy-intake deficit of 800 to 1,000 kcal.d-1; patients ate up to two meal replacements daily.
- Diet and exercise: Besides the same diet as in the first treatment arm, patients exercised by walking or doing weight training for an hour three days a week.
- Exercise-only (control): These patients exercised without dieting.
The goal of both diet groups was to lose at least 10% of their body weight. Participants met in groups, and Dr. Messier said such support contributed to the high retention rate (88%).
It’s quite remarkable that even if the patients had failed two or more TNF-inhibiting agents, they still had a significantly increased response to tofacitinib.
—Gerd R. Burmester, MD
“At 18 months, all groups showed improved mobility, pain, and function, but diet and exercise was superior in virtually all measures,” Dr. Messier said.
An intent-to-treat analysis found that the diet–exercise group had about a 50% decrease in pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 47% improvement in the WOMAC physical function score. These improvements were significantly better than in the other groups (P<.001 and P<.005, respectively). Participants who both dieted and exercised lost 11.4% of their body weight (mean of 10.6 kg).
Compared with the other groups, the diet–exercise group significantly quickened their walking speed (12% faster; P=.005). “It was faster than healthy, middle-aged women,” Dr. Messier said.
Two audience members called the results “very impressive.”
Juvenile Idiopathic Arthritis
A trial of aggressive multidrug treatment within a year after diagnosis of polyarticular juvenile idiopathic arthritis (JIA) failed to meet its primary endpoint of inducing clinically inactive disease in six months (abstract 721).
However, the study presenter, Carol A. Wallace, MD, professor of pediatrics and chief of pediatric rheumatology at Seattle Children’s Hospital and Research Institute, said they used a “very stringent” definition of inactive disease. She called “remarkable” that one-third of the 85 patients overall had clinically inactive disease at six months, and 14% had clinical remission due to medications.
Dr. Wallace concluded, “The earlier after disease onset that the patient started treatment, the likelihood of achieving inactive disease by six months increased logarithmically.”
This study was published in Arthritis & Rheumatism.2 Dr. Wallace reports receiving research grants from the National Institutes of Health, Pfizer, and Amgen, and consulting fees from Bristol-Myers Squibb.
Kathleen Louden is a medical writer based in the Chicago area.
References
- Mukerjee D, St George D, Knight C, et al. Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis. Rheumatology. 2004;43:461-466.
- Wallace CA, Giannini EH, Spalding SJ, et al, for the Childhood Arthritis Rheumatology Research Alliance. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis [published online ahead of print December 19, 2011]. Arthritis Rheum. doi: 10.1002/art.34343.
