SAN DIEGO—Daniel Solomon, MD, MPH, professor of Medicine at Brigham and Women’s Hospital and Harvard Medical School, Boston, captured the high points of the past year’s clinical research on rheumatic diseases—touching on medical therapy, genetics, the effects of bariatric surgery and diet—in a Year in Review session at the 2017 ACR/ARHP Annual Meeting.
Based on input from experts on the literature published from October 2016 to November 2017, Dr. Solomon highlighted the following studies:
Secukinumab & Ankylosing Spondylitis
In the double-blind, randomized, controlled trial, MEASURE 1, researchers compared the IL-17A inhibitor, secukinumab, with placebo in 371 patients with ankylosing spondylitis. It was a 24-month trial with a 36-month extension.1 The results were published in Arthritis & Rheumatology.
Researchers found significantly greater improvements on three patient-reported outcome scales—the BASDAI, SF36 and ASQoL—with the levels of minimal clinically important difference reached.
“These [results] appear to be sustained and suggest benefits patients will appreciate,” Dr. Solomon said.
Diet & Serum Urate
In a study published in Arthritis & Rheumatology, researchers compared the uric acid levels of patients on the Dietary Approaches to Stopping Hypertension (DASH) diet to patients not on the DASH diet, which comprises fruits, vegetables, grains and other foods deemed healthy.2
“How much can dietary manipulation change serum uric acid?” he asked. “This is an age-old question that we all wonder about when we’re seeing patients with gout.”
Patients received a low-, medium- and high-sodium diet in successive months. Researchers found patients in the DASH diet, low-sodium group had no change in uric acid levels compared with baseline. But during their months on medium- or high-sodium intake, a significant lowering in uric acid levels occurred. Patients not on the DASH diet had statistically significant increases in serum urate (SUA) when on the low-sodium diet, but experienced no change during their medium- and high-sodium months.
They also found that those in the DASH group with a baseline SUA of 6–7 mg/dL had a reduction of 0.8 mg/dL, and those with a baseline of 7 mg/dL or higher had a reduction of 1.3 mg/dL.
“This is proof of the concept that in specific subgroups, diet can effectively lower serum urate,” Dr. Solomon said.
Systemic Sclerosis & Mortality Risk
An observational study, published in Arthritis & Rheumatology, involved cohorts similar in makeup from Australia, Canada and Spain, including 1,070 patients with incident systemic sclerosis (SSc) and 3,218 patients with prevalent SSc.3
Researchers found the risk of mortality was a three- to fourfold increase in risk of death for these patients, with about 11–25 years of life lost in these groups. Cardiac, lung, gut and renal complications were the most common causes of death.
The Genotype of JIA
A study published in Annals of the Rheumatic Diseases included about 5,000 patients with juvenile idiopathic arthritis (JIA) and 14,000 controls. Researchers conducted fine mapping of the major histocompatibility complex (MHC) and looked at subtypes of JIA and their relationship to the MHC.4
They found oligoarthritis and RF-negative and RF-positive polyarthritis all share an HLA-DRB1 variant as their primary association—similar to what is seen in adult-onset rheumatoid arthritis (RA). Enthesis-related arthritis is associated with HLA-B27. And systemic JIA has a completely distinct set of associations.
“Future JIA classification criteria may be based more on genotype, and not only clinical presentation,” Dr. Solomon proposed.
IL-1 Antagonist & CV Risk
Dr. Solomon drew attention to a study, published in the New England Journal of Medicine, that examined whether canakinumab, an IL1-beta blocker, reduces repeat cardiovascular (CV) events in patients with elevated levels of high-sensitivity C-reactive protein (hsCRP).5
Although these findings are somewhat outside the rheumatology sphere, he highlighted them, saying, “it’s very important for all of us to be aware that immunomodulators are being tested for cardiovascular disease.”
More than 10,000 patients were enrolled in the study, with the outcomes of those taking canakinumab compared with those taking placebo. All patients had a prior myocardial infarction (MI) and hsCRP of at least 2 mg/L.
Researchers found patients taking 150 mg canakinumab had a 17% reduction in MI, stroke, CV death, unstable angina with hospitalization or urgent revascularization. A subanalysis found patients with the largest hsCRP reduction benefited the most, with a 30% reduction in CV events compared with placebo-treated patients.
“Immunosuppression with an IL-1 antagonist reduces CV events, with the success based on inflammation reduction,” Dr. Solomon said.
Intra-Articular Triamcinolone
In a double-blind, randomized controlled trial, researchers compared intra-articular triamcinolone with intra-articular saline in patients with symptomatic knee osteoarthritis with synovitis. Researchers enrolled 140 patients in the study, which was published in JAMA.6
They found both intra-articular steroids and saline are associated with reduced pain and improved function, but that intra-articular steroids may cause cartilage damage.
Bariatric Surgery & Psoriasis
In an observational study from JAMA Surgery, researchers analyzed the rates of psoriasis and psoriatic arthritis in 12,364 patients who underwent gastric bypass and 1,071 patients who underwent gastric banding.7 The capacity of the stomach is reduced in both procedures.
Using presurgery patients as their controls, researchers found gastric bypass reduced psoriasis by half and psoriatic arthritis by 70%, both statistically significant results. Gastric banding did not produce any significant reduction in risk.
“Gastric bypass associates with a reduced risk of PsO and PsA, possibly providing insights into metabolic correlates associated with PsO and PsA,” Dr. Solomon said. The results are only hypothesis generating, he cautioned.
Biologic DMARDs & Cancer Risk
Dr. Solomon said an observational study in JAMA Internal Medicine was important because “this is a typical patient question [for which] we need better data.”8
The study combined Swedish RA cohorts with cancer registries. Researchers found no increased cancer risk for TNF inhibitors across patients grouped by duration of use, even past four years of use. Researchers did find a “suggestion” of an increased risk with abatacept compared with TNF inhibitors for squamous cell skin cancers and melanoma, findings Dr. Solomon said “need further analysis.”
But overall, he said, “These results should increase confidence that TNF inhibitors are not associated with malignancy.”
Thomas R. Collins is a freelance writer living in South Florida.
References
- Deodhar AA, Dougados M, Baeten DL, et al. Effect of secukinumab on patient-reported outcomes in patients with active ankylosing spondylitis: A phase III randomized trial (MEASURE 1). Arthritis Rheumatol. 2016 Dec;68(12):2901–2910.
- Juraschek SP, Gelber AC, Choi HK, et al. Effects of the dietary approaches to stop hypertension (DASH) diet and sodium intake on serum uric acid. Arthritis Rheumatol. 2016 Dec;68(12):3002–3009.
- Hao Y, Hudson M, Baron M, et al. Early mortality in a multinational systemic sclerosis inception cohort. Arthritis Rheumatol. 2017 May;69(5):1067–1077.
- Hinks A, Bowes J, Cobb J, et al. Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases. Ann Rheum Dis. 2017 Apr;76(4):765–772.
- Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017 Sep 21;377(12):1119–1131.
- McAlindon TE, LaValley MP, Harvey WF, et al. Effect of intra-articular triamcinolone vs. saline on knee cartilage volume and pain in patients with knee osteoarthritis: A randomized clinical trial. JAMA. 2017 May 16;317(19):1967–1975.
- Egeberg A, Sørensen JA, Gislason GH, et al. Incidence and prognosis of psoriasis and psoriatic arthritis in patients undergoing bariatric surgery. JAMA Surg. 2017 Apr 1;152(4):344–349.
- Wadström H1, Frisell T1, Askling J, et al. Malignant neoplasms in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors, tocilizumab, abatacept or rituximab in clinical practice: A nationwide cohort study from Sweden. JAMA Intern Med. 2017 Nov 1;177(11):1605–1612.
