Tag Archives: psoriasis

New Anti-Inflammatory Drugs Will End Anti-TNF Dominance

Tumor necrosis factor inhibitor drugs began to dominate treatment of inflammatory diseases like rheumatoid arthritis, psoriasis, and the inflammatory bowel diseases ulcerative colitis and Crohn’s disease a little over a decade again. Now, the time when the importance of the anti-TNFs will wane and newer drugs will take their place is clearly visible on the horizon. It hasn’t happened yet, but the era of anti-TNF dominance for treating inflammatory diseases that persisted throughout the 2000s will end in the next 5 years.

The anti-TNF era began in 1998 with the approval of etanercept (Enbrel) for rheumatoid arthritis and infliximab (Remicade) to treat Crohn’s disease. In subsequent years, the list of approved anti-TNFs expanded to include adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia), and the approved indications grew to include many inflammatory disease of joints, the GI tract, and skin. The anti-TNFs revolutionized inflammatory disease treatment and made treatment to remission possible for many patients.

tumor necrosis factor (green, purple, black) and TNF receptors (blue)/courtesy Bassil Dahiyat; Science

But reports from just the past month show that new agents are overtaking the anti-TNFs.

In May, I reported from Digestive Disease Week on phase III trial results with vedolizumab, which was compared against placebo for patients with ulcerative colitis. One of the study investigators noted that vedolizumab beat the placebo arm for steroid-free clinical remission by 30 percentage points. “Nothing else is that good,” Dr. William Sandborn, professor of medicine and chief of gastroenterology at the University of California, San Diego, told me, and the benchmark he had in mind was the performance of the anti-TNFs in similar patients.

More recently, at the European Congress of Rheumatology earlier this month I heard a report on a head-to-head comparison of the anti-IL-6 drug tocilizumab (Actemra) and the anti-TNF adalimumab in patients with rheumatoid arthritis. After 24 weeks of monotherapy, patients on tocilizumab had nearly a fourfold higher remission rate than patients on adalimumab. Though the monotherapy trial design did not mimic the way most rheumatoid arthritis patients get treated, the new drug tocilizumab absolutely blew adalimumab out of the water in a rare head-to-head comparison among different classes of anti-inflammatory drugs.

And at the same meeting several talks highlighted another new anti-inflammatory class of agents coming soon to the U.S. market, the Janus kinase (JAK) inhibitors, such as tofacitinib, which is expected to received FDA approval later this summer. Phase III results show that tofacitinib has safety and efficacy that seems at least comparable to anti-TNF drugs, with the advantage of oral dosing.

Vedolizumab, tocilizumab, and tofacitinib are just the tip of new waves of anti-inflammatory drugs that will soon substantially alter a landscape that the anti-TNFs have mostly had to themselves for the past 14 years. For the moment, the anti-TNFs have the advantage of a longer track record for safety, but changing that is only a matter of time.

—Mitchel Zoler (on Twitter “mitchelzoler)

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Filed under Allergy and Immunology, Dermatology, Drug And Device Safety, Family Medicine, Gastroenterology, Health Policy, IMNG, Internal Medicine, Practice Trends, Primary care, Rheumatology, The Mole

Are Psoriasis Patients Better Off With Biologics?

That’s the question Dr. Kenneth Gordon of the Pritzker School at the University of Chicago posed to colleagues at the American Academy of Dermatology’s annual meeting in New Orleans.  It was not meant to be rhetorical.

Given the huge pressure to use the new therapies – from patients, pharmaceutical manufacturers, and in some cases, the dermatologist’s own desire to use what appears to be the latest and greatest – there are a lot of potential costs.

Via Flickr Creative Commons user walknboston

The drugs, which include Amevive (alefacept), Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), and Stelara (ustekinumab), are hugely expensive (for a list of these drugs and their mechanisms, go here). Plus, there is a human cost – many of these biologics have the potential to cause infections, demyelinating disorders like multiple sclerosis, and cancer.

Psoriasis is a lifelong disease, and thus, therapies are taken more or less for life, noted Dr. Gordon, who also heads dermatology at the Northshore University Health System. But what is known about the long term safety of these biologics? There is little-to-no data beyond trial periods of 12-24 weeks in psoriasis patients. And although some of the drugs have been studied for longer in rheumatoid arthritis, Dr. Gordon said that it is not instructional to extrapolate the data to psoriasis.

When the first biologic came on the market in 2003, there was a great deal of excitement, he said.  At that time, at least half of patients he treated were on methotrexate.

In his presentation, Dr. Gordon delved through the available data on efficacy and long term safety of older therapies like methotrexate, acitretin, and cyclosporine, and compared that to the biologics’ track record.  So far, though there’s a big gap between knowledge and use for both the older and newer therapies.

What he concluded was that for moderate-to-severe patients, biologics probably pack a more powerful punch.  Methotrexate is still a first-line choice for many psoriasis patients in his practice who are not as ill, but he says he still thinks of the drug as having had its heyday in the 1970s.

Where do biologics fit in your practice? Have your patients been better off since the advent of the therapies?

— Alicia Ault (on Twitter @aliciaault)

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Filed under Allergy and Immunology, Dermatology, IMNG, Rheumatology