Parting Words from Jerry Bagel, MD

I became the psoriasis editor for Practical Dermatology® magazine in 2004. The biologic revolution in psoriasis commenced in February 2003 with the FDA approval of alefacept (Amevive, Astellas Pharma US) which could be given intravenously (7.5mg) and intramuscularly (15mg).

Many psoriasis patients were happy to try a new treatment option. Previous therapeutic choices included phototherapy three times a week for 12 weeks; psoralen and ultraviolet A (PUVA) with its corresponding risk of skin cancer; methotrexate with its risk of liver damage; cyclosporine with its risk of renal toxicity; and acetretin, which is teratogenic and causes numerous nuisance side effects (i.e., cheilitis and alopecia).

Unfortunately, Amevive only achieved a Psoriasis Area and Severity Index 75 (PASI 75) 20 percent of the time—although PASI 50 was considered a good improvement back then. The next biologic approved was efalizumab (Raptiva, Genentech), a subcutaneous injection administered weekly that achieved PASI 75 about 40 percent of the time. In 2010, however, there were four deaths from progressive multifocal leukoencepholopathy associated with Raptiva, and Genentech voluntarily removed it from the market.

The first biologic to make bigger waves was the tumor necrosis factor alpha (TNF-a) blocker etanercept (Enbrel, Amgen), which is still in use, especially given its approval for children as young as four. Patients on Enbrel can achieve a PASI 75 about 50 percent of the time. Next up was infliximab (Remicade, Janssen Biotech), which is given via IV infusion. It was utilized for the most severe psoriasis cases, most often in conjunction with methotrexate. Remicade is not utilized nearly as much today, due to the higher efficacy seen with the newer agents. Humira (adalimumab, AbbVie), another TNF inhibitor, achieves PASI 75 in about 71 percent of patients.

Ustekinumab (Stelara, Janssen) was a major breakthrough in that it only required a 12-week dosing schedule, is relatively safe, and boasts PASI 75 about 67 percent of the time.

Then came the next generation of IL-17 inhibitors, secukinumab (Cosentyx, Novartis), ixekizumab (Taltz, Lilly), and brodalumab (Siliq, Ortho Dermatologics). Taltz and Siliq show PASI 100 rates reaching 50 percent in their labels. Most recently the IL-23 inhibitors guselkumab (Tremfya, Janssen), tildrakizumab-asmn (Ilumya, Sun Pharmaceuticals), and Risankizumab (Skyrizi, AbbVie) show PASI 100 rates that in some cases approach 60 percent. We have seen a similar trajectory in treating psoriatic arthritis (PsA) with biologics.

In addition to the seismic change in how we treat these diseases, I have borne witness to a whole new way of thinking about them. Psoriasis is increasingly viewed as an inflammatory disease with noted systemic consequences. This new thinking has encouraged us to treat psoriasis more aggressively, so we can clear the skin and hopefully forestall or prevent any downstream consequences. Dermatologists now recognize PsA as a frequent component of psoriasis. Evaluating for morning stiffness, enthesitis, dactylitis ,and implementing biologic therapy has proven to delay the radiographic progression of joint destruction and has been a major advance in decreasing disability associated with PsA.

Hope for a Cure

The most common question I get from a new patient is, “Will I have to be on this treatment forever?” My response is that psoriasis is a chronic immunologic disease. If you were diagnosed with diabetes, you would need long-term treatment, and that is the case with psoriasis, as well. Fortunately, advances in psoriatic therapy over the past 15 years have been remarkable. Today’s treatments are better and safer than we could have imagined. (The only disease state with a greater advance than psoriasis is HIV.) I look forward to finding the cure, and believe it’s coming. Meanwhile, I see a lot of patients today who are very happy.

I couldn’t have said any of that when I started as editor of this section.

Editor’s note: We thank Dr. Bagel for his thoughtful contributions over the years. He was a joy to work for and with. We wish him luck in all future endeavors. Get Everything Bagel here.

Interested in contributing to Practical Dermatology® on a regular basis? We are in the process of appointing a new psoriasis feature editor. Reach out to dmann@bmctoday.com to learn more.