AAD Survey: One-Third of Americans Flunk Basic Quiz on Skin Cancer and Sun Exposure

With the approval of Janssen’s Tremfya (guselkumab) last year as the first IL-23 inhibitor FDA-approved for the treatment of active psoriatic arthritis (PsA)—its psoriasis (PsO) indication dates to 2017—have come new data about the biologic’s clinical effects.

Lloyd S. Miller, MD, PhD, Vice President, Immunodermatology Disease Area Stronghold (DAS) Leader at Janssen, spoke with Practical Dermatology® magazine.

Janssen will “redefine” treatment of immune mediated diseases.

“Janssen is redefining the treatment of immune mediated diseases at the intersection of unmet need, deep disease insights, and novel pathway science. And this really means that we are dissatisfied by that status quo and we’re working to target novel immune pathways to help patients live their best, healthy, and productive lives through restoring immune balance,” says Dr. Miller.

Tremfya exemplifies a “Pathway approach.”

“Our science regarding Tremfya in PsO and PsA is an excellent example of our pathway approach,” Dr. Miller says. It is the first biologic to inhibit IL-23, a pathway implicated in PsO, PsA, and other immune diseases.

“Tremfya is a first-in-class, best-in-class IL-23 therapy with five-year efficacy and safety data in psoriasis and now in psoriatic arthritis. We will focus on this same pathway-type approach as we study new therapies in new disease indications, such as atopic dermatitis, hidradenitis suppurativa, and other immune mediated skin diseases.”

Rebalancing the immune system is a focus.

Rather than focusing on immune suppression, as has been done historically, “our approach is pivoting toward a goal of restoring immune balance or homeostasis of the immune response,” Dr. Miller says. “Our future therapies will be more effective in restoring this immune homeostasis by applying new and different mechanisms to block the accelerators of the immune system. IL-23 is a pro-inflammatory cytokine or immune ‘accelerator.’ In patients with PsO and PsA, there’s apparent overproduction and hyper-responsiveness to this IL-23 pathway. Tremfya blocks IL-23 and can balance the immune system, improve the symptoms of psoriasis or psoriatic arthritis, and other immune mediated diseases.

“We hope that this concept of focusing on immune balance and homeostasis can be translated to other diseases in dermatology, so we no longer suppress the immune system and have side effects of increased infections and other issues with immunosuppression.”

Holistic approaches benefit patients.

“It’s very important from a holistic standpoint to treat the patient’s symptoms,” says Dr. Miller. “If they have psoriasis and then develop psoriatic arthritis, we need to now treat the symptoms involved in PsA. The two are very, very connected. Fatigue is a really important symptom of psoriatic arthritis that patients complain about. They also have stress, depression, behavioral changes, body image issues, and reduced work productivity. And psoriasis also has symptoms that can cause feelings of embarrassment, self-consciousness, and depression. Patients with psoriasis can also feel rejection, shame, and guilt because of their disease.”

He notes that dermatologists have the ability to treat skin and joint symptoms, but should be prepared to refer to rheumatologists if needed.

Data tell the story.

“At the Coastal Dermatology meeting in October 2020, we presented nearly five years of data for psoriasis, showing 84 percent of patients achieved a PASI 90 response, which was very impressive over five years. Just having that long-term efficacy data is something that we’re very proud of. In addition, there were no new safety concerns over 264 weeks and no new safety signals.

“A key abstract at the EADV congress highlighted the Phase 3 DISCOVER-2 study for Tremfya and psoriatic arthritis, showing patients treated with Tremfya for joint pain had a greater likelihood of also becoming free of psoriasis symptoms at week 24; a greater proportion of psoriatic arthritis patients treated with Tremfya reported their skin disease no longer had any impact on their health-related quality of life as measured by the DLQI versus placebo,” Dr. Miller says.

“Data presented at the American College of Rheumatology meeting demonstrated Tremfya improves the symptom of fatigue in adult patients with PsA, a response maintained through 52 weeks of active treatment.”

“Data from a network meta-analysis published in Rheumatology showed Tremfya delivered the highest overall achievement of skin clearance, with joint symptom achievement comparable with IL-17A inhibitors and subcutaneous TNF inhibitors.”

“Key data at the recent AAD meeting highlighted the Phase 3 VOYAGE 2 study for Tremfya in PsO and Phase 3 DISCOVER-1 and DISCOVER-2 studies for Tremfya in PsA. VOYAGE 2 results showed skin clearance rates maintained at 5 years with 55.5 percent of patients achieving an IGA of 0 and 53 percent achieving PASI 100 response. Data from the studies showed robust joint symptom improvement through 52 weeks: Tremfya improved psoriatic disease activity in joints and across multiple domains through week 52 in both trials as measured by the Disease Activity Index for PsA, Minimal Disease Activity, Very Low Disease Activity and remission using Disease Activity Index for PsA.”

“Recent data published in Rheumatology show treatment with Tremfya in PsA resulted in higher proportions of resolved enthesitis by week 24, with maintenance of resolution rates through one year. This is an important finding as many patients with PsA are affected with an array of challenging symptoms like enthesitis when diagnosed with this multi-faceted disease.”

To gain a better understanding of the risk of skin cancer associated with antihypertensive medication, researchers led by Aaron Drucker MD, ScM, FRCPC, a scientist at Women’s College Research Institute and a dermatologist at Women’s College Hospital in Toronto, Ontario, Canada, reviewed data of nearly 303,000 adults in Ontario over age 65 who were prescribed medications for hypertension and compared their skin cancer histories with those of more than 605,000 adults who weren’t taking antihypertensive drugs.

They found that higher cumulative exposure to thiazide diuretics was associated with higher rates of keratinocyte skin cancers, including basal cell carcinoma, squamous cell carcinoma, advanced keratinocyte carcinoma, and melanoma. However, there was no consistent evidence of association between other antihypertensive classes such as angiotensin-converting enzyme (ACE) inhibitors, beta blockers, angiotensin II receptor blockers (ARBs), and calcium channel blockers and keratinocyte carcinoma or melanoma, according to the study that appears in CMAJ. Dr. Drucker discussed the new findings, their implications and the next steps with Practical Dermatology®.

Why is this topic important to study?

Aaron Drucker, MD: Skin cancer is very common, so identifying modifiable risk factors beyond UV radiation protection is important. Because some antihypertensive medications are photosensitizing, people have hypothesized that they might increase skin cancer risk. In particular, hydrochlorothiazide has been implicated as potentially increasing skin cancer risk, and regulators like the FDA have issued warnings about it.

Describe the research and your findings.

Dr. Drucker: We conducted a cohort study of older adults using population-based data for Ontario, Canada. We matched patients starting an antihypertensive medication with patients starting an unrelated medication and followed them over time to update their cumulative dose of each antihypertensive medication class and to see if they developed skin cancers, including keratinocyte carcinoma (basal and squamous cell carcinoma) and melanoma. We found that most antihypertensive classes, including ACE inhibitors, ARBs, calcium channel blockers and beta blockers, were not associated with increased skin cancer risk. Consistent with previous studies, we found that thiazide diuretics were associated with increased risk of both keratinocyte carcinoma and melanoma.

What is the next step?

Dr. Drucker: It is important to understand which patients may be most affected by the association between thiazides and skin cancer. We could not look at this in our study, but it is likely that patients with fair skin and a history of previous skin cancers or sun damage, such as actinic keratosis, are most at risk. For patients with skin cancer risk factors on or considering starting thiazides, they should discuss with their physician whether the benefits of those medications outweigh the risk of skin cancers.

The dermatology community is celebrating the lives of two pioneering women in the field. Read more at PracDerm.com/Remembrance

Melanie Grossman, MD (1962 - 2021)
Dr. Grossman was a trailblazer in her field and among the first female dermatologists to embrace energy-based devices.

Marta Rendon, MD (1957–2021)
Born in Medellin, Columbia, Dr. Rendon enjoyed an illustrious and fulfilling career in dermatology with many important achievements.