An observational study to investigate how new therapies for rheumatic diseases perform across different conditions has revealed that they may be more successful in certain conditions. The data is presented today at the Annual European Congress of Rheumatology in Amsterdam, the Netherlands. An increasing proportion of patients with rheumatic conditions such as ankylosing spondylitis (AS), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) now receive anti-TNF treatment – a newer group of drugs that are used to reduce inflammation and manage disease activity*. Study lead Dr Marte Heiberg, of the Dept of Rheumatology, Diakonhjemmet Hospital, Oslo, told delegates: “Many studies have focused on the efficacy of these drugs, however less is known about the comparative real-life performance of these drugs across different diagnostic groups”.

The study was conducted across 5 Norwegian Rheumatology Departments and included 796 RA patients, 162 PsA patients and 211 patients with a diagnosis of AS. All patients were on an anti-TNF treatment regimen of infliximab, etanercept or adalimumab +/- methotrexate (MTX). The primary outcome was the number of patients still on therapy at one year – known as the adherence to therapy. RA was used as the reference group and within each diagnostic group, the adherence to anti-TNF monotherapy versus TNF+MTX was compared.

The relative risk for withdrawal from TNF+MTX versus anti-TNF monotherapy was 0.54 for RA patients, 0.49 for PsA patients and 0.83 for AS patients, demonstrating that combination treatment strategy of anti-TNF+MTX worked better than anti-TNF monotherapy in patients with RA and PsA. Although the crude one-year overall drug adherence rates for anti-TNF therapy were superior in patients with PsA and AS compared to RA, after adjusting for age, gender and concomitant MTX, the adherence to anti-TNF treatment were similar in patients with RA and PsA whereas the adherence to anti-TNF treatment was superior in patients with AS compared to RA.

Dr Heiberg stated: “This is a fresh insight into the performance of these very good treatment options and helps to build a greater picture of how they work across the different rheumatology disease areas. Whilst many of the anti-TNFs were originally used in RA, it is most interesting to note that they could actually work for a comparatively larger proportion of patients with an AS diagnosis.”

Rheumatoid arthritis patients getting little or no relief from conventional small-molecule drugs and injectable biologic drugs saw substantial improvement in their condition from daily use of an experimental compound in a large 24-week study led by a Stanford University School of Medicine investigator.

A paper describing the results of the double-blind, randomized phase-3 clinical trial will be published July 23 in JAMA.

“For patients who haven’t done well on other therapies, these findings are cause for optimism, enthusiasm and hope,” said Mark Genovese, MD, professor of immunology and rheumatology and principal investigator of the study.

Stanford Health Care offers services to rheumatoid arthritis patients through its immunology and rheumatology clinic. As clinical chief, Genovese spends 3 half-days per week in the clinic, where he regularly sees and treats rheumatoid arthritis patients.

He is the paper’s lead author. The senior author is Tsutomu Takeuchi, MD, PhD, professor of rheumatology and clinical immunology at Keio University School of Medicine in Tokyo, Japan.

Rheumatoid arthritis is a progressive, systemic autoimmune disease affecting at least 1 in every 100 people worldwide. For reasons that aren’t understood, 3 of every 4 people with the disorder are women. While its most visible hallmarks are pain, stiffness, inflammation and eventual deterioration of joints, patients also are at heightened risk for cardiovascular disease and other inflammatory complications.

In clinical trials, about 70% of rheumatoid arthritis patients have appeared to benefit initially from small-molecule therapies in a pill form, such as methotrexate, said Genovese, who is the James W. Raitt M.D. Professor. However, “in the real world, adherence to any of them is more like 50%,” he said. Patients for whom the conventional small-molecule drugs fail are switched to pricey, injectable, bioengineered-protein drugs, including three of the world’s top-15 biggest-selling drugs in dollar sales. But these drugs, too, fail among about half the rheumatoid arthritis patients who use them, Genovese said.

Selective JAK-1 inhibitor

The experimental compound, filgotinib, is a selective JAK-1 inhibitor. It works by preferentially blocking 1 of a set of 4 closely related enzymes required for certain inflammatory signaling processes within cells. Two other compounds that are similar in mechanism of action to filgotinib but that impede JAK enzyme family members less selectively are licensed in the United States for use by rheumatoid arthritis patients, but only at low doses or with warning labels due to side effects.

The trial was conducted in 114 centers in 15 countries, mostly in North America and Europe. The 449 participants averaged 56 years of age, and about 80% of them were female. They were randomized to 1 of 3 study arms, in which they received daily doses of either 200 milligrams of filgotinib, 100 milligrams of filgotinib or a placebo for 24 weeks. All participants had moderately to severely active rheumatoid arthritis despite treatment with one or more biologic therapies.

The primary goal of the study was to observe whether there was an improvement at 12 weeks into the trial of at least 20% on a measure of joint swelling and tenderness called the ACR20 that was established by the American College of Rheumatology. An important secondary outcome was a score indicating low disease activity in 28 predetermined joints on a test called the DAS28-CRP.

Compared with the placebo group, a significantly greater proportion of participants on both the high- and low-dose filgotinib regimens achieved the primary endpoint: a 20% improvement in symptoms as measured by the ACR20. Sixty-six percent of participants on 200 milligrams of filgotinib, and 57.5% of those on 100 milligrams, fulfilled this criterion, versus only 31.1% of those on placebo.

Of equal or even greater importance, Genovese said, was the participants’ improvement on the DAS28-CRP at both 12 and 24 weeks. By 12 weeks, 40.8% of those on the 200 milligram dose of filgotinib and 37.3% of those on 100 milligrams had reached the status of low disease activity as measured by the DAS28-CRP, as opposed to only 15.5% of those on the placebo regimen. These outcomes continued or improved over the course of the trial. By 24 weeks, 48.3% of the high-dose filgotinib recipients and 37.9% of those on the low dose had reached low-disease-activity status.

By week 12 of the trial, 22.4% of high-dose and 25.5% of low-dose filgotinib recipients, but only 8.1% of placebo recipients, had DAS28-CRP scores indicating outright remission. By week 24, high-dose recipients had a remission rate of 30.6%; low-dose recipients, 26.1%; and placebo recipients, 12.2%.

Improvement seen early on

The drug’s benefits to participants became apparent soon after the trial’s onset. “We could see improvements as early as two weeks into the trial,” Genovese said.

Also telling was a substantial difference among the study arms in how many participants completed the 24-week trial. Of the 148 participants in the placebo arm, 51 dropped out before completion. Only 20 of the 148 high-dose recipients and 34 of the 153 low-dose recipients dropped out.

Investigators’ early concerns about increased susceptibility to infections, or the re-emergence of active forms of prior infections, such as tuberculosis or shingles, were assuaged by the relative smattering of such adverse events, compared with placebo.

Notably, patients for whom at least three different biologic therapies provided insufficient relief did as well in this trial as those who’d derived insufficient relief from just one biologic therapy, Genovese said.

“We found that those high levels of response were independent of how many drugs you’d failed, and independent of which drugs you’d failed,” he said.

Overall response rates to filgotinib appear to surpass those of the other commercially available JAK inhibitors at doses approved for use in the United States, he said.

“This novel drug works exceptionally well in patients who’ve already failed traditional therapies for rheumatoid arthritis,” he said.

A breakthrough in understanding the way atoms move across cell membranes in the human body could pave the way for the development of new treatments for inflammatory diseases such as rheumatoid arthritis.

Scientists at the University of Leeds have identified a previously unknown natural mechanism that opens ion channels – proteins at the cell surface that act as doorways into and out of cells – through the naturally occurring protein thioredoxin.

Ion channels allow movement of ions – electrically charged atoms – across the cell membrane to carry out various functions such as pain transmission, timing of the heart beat, and regulation of blood glucose. Often, they need to be stimulated to open and, until now, two main groups of activating mechanisms have been acknowledged: changes in cell voltage and binding of chemical factors.

In a paper published today (03 January) in Nature, Professor Beech and colleagues from the University’s Faculty of Biological Sciences reveal that thioredoxin works in a different manner: it activates an ion channel by donating electrons to it, in a process Professor Beech likens to “an electronic on-switch”.

“Thioredoxin is naturally present in cells and is secreted to help the body counter stressful chemical reactions that occur in inflammation, which can damage cells,” he explains. “We already knew that inflammatory diseases cause the production of high levels of thioredoxin – in fact with rheumatoid arthritis, it’s striking how much is present in affected joints. But we didn’t know until now that thioredoxin can also activate ion channels, conferring additional protective potential and offering opportunities for mimicking the effect with drugs.”

“It would seem that the body’s own natural defences have provided us with new understanding that could be significant in the development of future treatments for arthritis and related diseases,” he says.

n this video, I’m raising awareness on the fact that arthritis doesn’t care who you are, and it’s a disease that has impacted people for ages. I even talk about a model featured in a famous painting, who is suspected to have had rheumatoid arthritis back in the 1400s! It can affect anyone, even public figures. Here are some people you should know about who are not only inspiring but have used their platforms to make change within the arthritis community.