Filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, showed positive results in a phase II placebo-controlled study for active psoriatic arthritis (PsA). Eighty percent of patients in the filgotinib arm achieved ACR20 at 16 weeks versus 33.3 percent for placebo (p<0.0001), and 45.2 percent had PASI75 versus 15 percent for placebo (p=0.0034). Adverse event rates were similar between the two groups.
Results of the EQUATOR study were presented during Plenary Session II on Monday and published simultaneously in The Lancet.
“The effect of filgotinib was rapid,” said Philip J. Mease, MD, Swedish Medical Center and University of Washington. “As early as one week into treatment, one could see response. We need to see phase III studies.”
EQUATOR randomized 131 patients with PsA in seven Eastern and Western European countries to filgotinib or placebo over 16 weeks.
The JAK1 pathway has been implicated in the pathogenesis of PsA, Dr. Mease noted, and filgotinib inhibits most of the key pathways in this disease.
It also shows broad inhibition of cytokine pathways, raising the potential for unintended side effects. There were few differences in laboratory parameters between filgotinib and placebo, Dr. Mease reported, while pain and quality-of-life scores improved significantly on treatment.
11-year Scleroderma follow-up
An 11-year follow-up to the Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial showed clear superiority for myeloablative autologous hematopoietic stem cell transplantation in patients with severe disease. This long-term follow-up confirms five-year results published earlier this year in the New England Journal of Medicine.
SCOT participants were randomized to either cyclophosphamide or hematopoietic stem cell transplantation between 2006 and 2011 and followed for 54 months. All 75 patients had significant skin disease and internal organ involvement, primarily lung.
Researchers used scripted telephone calls and public death records to extend follow-up to 11 years for 57 percent of the original participants.
Transplantation patients had 80 percent survival versus 52 percent for cyclophosphamide (p=0.03). In the transplant group, 92 percent remained free of DMARD use versus 61 percent of the cyclophosphamide group (p=0.01). Patients in the transplant group also showed improved physical functioning and employment status compared to cyclophosphamide.
“Here is a frustrating, severe disease where you have improvement over a decade,” said Keith Sullivan, MD, James B. Wyngaarden Professor of Medicine at Duke University School of Medicine. “Follow your scleroderma patients’ pulmonary function frequently and get them to a transplant referral before their lung function declines to the point that transplantation is no longer an option.”
Drugs May Help RA-ILD
New genetic research suggests that agents used to treat idiopathic pulmonary fibrosis may also help rheumatoid arthritis patients with interstitial lung disease. RA patients with ILD have significantly poorer survival compared to patients without lung involvement.
ILD is clinically significant in five to 10 percent of RA patients but is present in up to half, said Pierre-Antoine Juge, MD, Bichat Hospital, Diderot University in Paris, France. RA-ILD and IPF show similar patterns of fibrosis, prognosis, and risk factors such as male sex, age, tobacco use and more. Those similarities suggest a common genetic background.
It was already known that the rs35705950 variant of the MUC5B gene, which encodes for Mucin 5B, increases the risk for IPF eight-fold. A genetic case-controlled association study across multiple populations in Asia, Europe, and North America found the rs35705950 variant increases the risk for RA-ILD five-fold.
“These results suggest that RA-ILD and IPF share genetic components, and we propose that IPF drugs be evaluated in IA-ILD,” Dr. Juge concluded.
Denosumab Beats Risedronate
Initial results of a head-to-head comparison of denosumab and risedronate in patients treated with glucocorticoids showed improved bone mineral density for denosumab at 12 months. Two-year data confirm those results.
“This study is very relevant to us as rheumatologists because we prescribe a lot of corticosteroids,” said Kenneth Saag, MD, MSc, Jane Knight Lowe Professor of Medicine at the University of Alabama Birmingham School of Medicine. “Many of our patients are not getting any kind of treatment or prevention for glucocorticoid-induced osteoporosis.”
The study followed patients taking at least 7.5mg/day corticosteroids for 24 months. The primary analysis showed greater BMD gains at both the lumbar spine and hip for denosumab. Two-year results showed superiority for denosumab at all measurement points. The separation in BMD was seen almost immediately, Dr. Saag said, and the separation continued to grow over the two years of follow-up.
There was no significant difference in bone turnover markers between the two agents while adverse events and serious infections were similar.
Fractures were recorded as adverse events, Dr. Saag noted, and the study was not powered to evaluate any differences between the two groups.
microRNA-128 May cause OA Damage
Based on genetic analysis of cartilage from osteoarthritis (OA) patients, inhibiting microRNA-128 may promote cartilage growth and reduce the impact of OA.
More than 3,000 microRNAs have been identified in human tissue, said Feng-Sheng Wang, PhD, Kaohsiung Chang Gung Memorial Hospital, Taiwan, but microRNA-128 is the most prevalent species in OA cartilage. This microRNA represses chondrocyte autophagy and enhances chondrocyte apoptosis, effectively down regulating the production of new cartilage. It also decreases chondrogenic differentiation, again reducing cartilage production.
Work in microRNA-128 knockout mice shows that repressing this epigenetic factor leads to high chondrogenic differentiation and cartilage overgrowth, which reduces cartilage erosion and improves physical performance.
“A treatment strategy that blocks microRNA-128 signaling could be very beneficial for cartilage anabolism,” Dr. Wang said.
PT, APM Outcomes Similar
Knee pain and meniscal tears are a frequent source of disability in middle age and later years. More than 400,000 arthroscopic partial meniscectomies (APMs) are performed annually in the U.S. alone, and even more patients get physical therapy (PT) referrals. Short-term trials show that PT and APM produce similar improvements, but there are few longer-term results.
Early results from the Meniscal Repair in Osteoarthritis Research (MeTeOR) trial found little difference in six and 12-month outcomes between PT and APM in patients 45 and older. A five-year follow-up found similar results.
“The improvements in pain and function seen earlier were maintained, on average, over five years,” said Jeffrey N. Katz, MD, MSc, Associate Physician at Brigham and Women’s Hospital. “Our findings support treatment as being preference-driven.”
The seven-center trial compared PT alone, APM alone, and PT that crossed over to APM. Data were collected using both medical records and patient questionnaires every six months. The primary outcome was the KOOS pain score. Cumulative incidence of total knee replacement (TKR) was a secondary outcome.
Pain scores were similar in the groups.