Conference Coverage

Experts review the year in rheumatology ... and what lies ahead


 

EXPERT ANALYSIS FROM RWCS 2018

– Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.

Here’s how they called it:

The top events in rheumatology during the last year

The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.

“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.

Dr. Alvin F. Wells (left) and Dr. Orrin M. Troum Bruce Jancin/Frontline Medical News

Dr. Alvin F. Wells (left) and Dr. Orrin M. Troum

Finally, therapeutic progress in osteoarthritis: “We have more than 10 drugs for rheumatoid arthritis that can slow or stop the disease process, and yet we have more than 30 million people with osteoarthritis that we have no drugs for. But I think there are finally some things on the horizon that look promising,” observed Orrin M. Troum, MD, of the University of Southern California in Los Angeles.

A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.

“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.

Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.

Dr. Anne M. Stevens Bruce Jancin/Frontline Medical News

Dr. Anne M. Stevens

These disorders, while uncommon, are a huge challenge for pediatric rheumatologists. They are sudden in onset, often recurrent, and have high morbidity and mortality. While many children with macrophage activation syndrome respond to anti-IL-1 therapy, a subset do not. Dr. Stevens credited a team of investigators at the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several university hospitals with proving that IL-18 is a key cytokine in some of these nonresponders. The investigators got the research ball rolling with their case report of a dramatic and swift response to tadekinig alfa in a child with life-threatening macrophage activation syndrome and extraordinarily high blood levels of IL-18 (J Allergy Clin Immunol. 2017 May;139[5]:1698-1701). As a result, a formal clinical trial is ongoing.

Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).

“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.

Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.

Dr. Arthur Kavanaugh Bruce Jancin/Frontline Medical News

Dr. Arthur Kavanaugh

“It’s an approach that makes sense: You use rituximab as a sort of induction therapy to deplete B cells, then serum levels of BAFF/BLys go sky high, so some weeks later you use belimumab to block that,” explained Dr. Kavanaugh, professor of medicine and director of the Center for Innnovative Therapy in the division of rheumatology, allergy, and immunology at University of California, San Diego.

Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.

“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.

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