Derms on Drugs Podcast Summary

Episode: Litfulo Lowdown: When to Wave Goodbye; Olumiant Showdown: Solo vs. Squad; Solar Shocker: More Sun Equals Less Death?
Date: January 31, 2025
Hosts: Dr. Matt Zirwas, Dr. Laura Ferris, Dr. Tim Patton
Special Guest: Dr. Richard Weller, University of Edinburgh
Produced by: Scholars in Medicine

Episode Overview

This episode dives into three hot dermatology topics: the new data on Litfulo (ritlecitinib) for alopecia areata, the effectiveness of Olumiant (baricitinib) solo versus in combination with phototherapy for vitiligo, and a provocative investigation into whether higher sun exposure could actually mean lower all-cause mortality. The hosts blend clinical acumen with irreverent banter, and the conversation is further enriched by the insights of Dr. Richard Weller, an expert on the health impacts of UV light.

The Big Three: Key Articles and Discussion Points

1. Litfulo Lowdown: When to Wave Goodbye

Article Discussion:

• Study: Post-hoc analysis from the Allegro Phase 2B/3 trial on ritlecitinib (Litfulo) for alopecia areata (AA)
• Findings:
  • Most responders at 24 weeks stayed responders at 48 weeks
  • The real news: up to a third of non-responders at 24 weeks became responders by 48 weeks
  • Complete non-responders at 24 weeks rarely improved by week 48
  • Factors for poor response: male sex, longer disease duration, more severe AA (higher SALT score), more eyebrow/eyelash involvement

Key Quotes:

• “If you've had nothing at six months, it's basically probably time to switch up and try a different agent or do something else.” — Matt (04:08)
• “A quarter to a third of non responders at week 24 actually did respond if you went out to week 48.” — Laura (03:35)

Practical Tips:

• Continuation to 48 weeks is reasonable only for partial responders at 24 weeks
• For true non-responders at 6 months, consider alternatives (add prednisone, use clobetasol under occlusion)
  • “If it's six months, you're not getting better, I'll add three months of prednisone or I'll try the clobetasol under occlusion.” — Matt (05:32)

2. Olumiant Showdown: Solo vs. Squad (Baricitinib & Phototherapy in Vitiligo)

Article Discussion:

• Study: RCT of baricitinib (Olumiant) with/without phototherapy for active non-segmental vitiligo in four French hospitals
• Protocol:
  • First 12 weeks: baricitinib or placebo, no light
  • Weeks 12–36: both groups get narrowband UVB and continue original pill
• Results:
  • Both groups improved with phototherapy, but the combination group (baricitinib + UVB) showed greater improvements in VASI scores and quality of life at certain time points
  • Noteworthy adverse event: one pulmonary embolus in the baricitinib group
  • Quality of life only diverged significantly at week 24

Notable Insights:

• “I was mostly shocked by how lousy narrowband UVB worked on its own... 24 weeks twice weekly.” — Matt (09:27)
• “Barry’s going to stop the active disease from progressing, then you hit them with a narrow band that’s going to allow the repigmentation.” — Tim (09:56)
• Adding topical agents (like bimatoprost) may provide extra benefit for facial vitiligo alongside topical JAKs

Clinical Pearls:

• Combo therapies (systemic JAK plus phototherapy) are more effective than monotherapies for active vitiligo
• Watch for systemic side effects (PE risk)

3. Solar Shocker: More Sun Equals Less Death?

Key Article:

• Study: UK Biobank analysis—higher natural UV exposure and indoor tanning associated with lower all-cause mortality (especially cardiovascular), despite higher skin cancer incidence
  • No increase in skin cancer deaths
  • Linear relationship: more sun, lower mortality, biggest effect on CVD

Debate & Skepticism:

• Vitamin D is a biomarker, not the mediator (“Vitamin D doesn’t help with any of this stuff.” — Matt, 13:50)
• Questions of confounding and causality raised by Laura and Tim

Practice Implications Discussed:

• “You risk-stratify....I think it makes more sense as opposed to just maybe saying what we tell our patients: ‘you need to protect yourself from the sun.’” — Tim (15:31)
• American sun guidance might differ from Europe/Australia due to latitude and skin type

Deep Dive: The Science of Sunlight & Health with Dr. Richard Weller

[17:31–41:52]

Main Insights:

• Mechanism: Vitamin D supplements don’t lower mortality—it's nitric oxide released in skin by UV exposure that delivers cardiovascular benefit
  • “When you give people vitamin D, it doesn’t do much...it’s a biomarker for sunlight exposure.” — Dr. Weller (17:31)
  • “The skin contains large stores of nitric oxide which are photo-released by UV...vasodilates, lowers blood pressure and high blood pressure is the biggest killer in the world today.” — Dr. Weller (19:17)
• Magnitude: 6 mmHg lower systolic BP in summer, correlates to ~23% reduction in CVD mortality
• Demographics: Skin color matters—a reduced BP effect in Black Americans due to less UV penetration
• Seasonality: Only half the blood pressure benefit is due to temperature, the other half is UV-specific ([21:03])
• Safety & Messaging: One size does not fit all—advice on sun exposure should differ based on individual risk, skin type, and local UV intensity
  • “Don’t get sunburned is the important message.” — Dr. Weller (28:12)
• Sunscreen: High SPF (lab conditions) blocks NO release in the skin, but real-world use is variable

Notable Quotes:

• “What does that mean? That means a reduction in your risk of death from cardiovascular disease of 23%. That is huge.” — Dr. Weller (22:13)

Caveats/American Context:

• “[America] is different. You guys live a way lot further south than we do...white skin in Europe and China evolved as an adaptation to the lack of sunlight there.” — Dr. Weller (29:59)
• “I am not saying sun beds make you live longer. This is an observational study...I am saying that sun seekers live longer.” (32:53)

Recommendations for Practice [33:13]

• Average-risk patients: Get some sun, don't burn
• High-risk (e.g., transplant recipients): Strict protection
• Guideline Evolution: Supports updated Australian guideline approach based on skin type
  • Different populations (e.g., aboriginal Australians, Ethiopian populations) have no detectable UV-induced skin cancer

Notable Quotes & Memorable Moments

• “UV exposure reduces cardiac risk by nitric oxide independent of vitamin D.” — Dr. Weller (summary of 19:17–23:58)
• “We used to — derms used to — win Nobel prizes, and now we sell 300 skincare lines.” — Tim (40:48)
• “I am not horrified of the sun.” — Tim (15:13)
• “We might be telling people: ‘get more UV, might increase your risk of skin cancer, but it'll reduce your risk of dying from all this other stuff even more.’” — Matt (13:50)

Additional Segments

The Little Three: Rapid-Fire Article Summaries

[41:58–56:02]

1. Dupilumab Benefits in Immunotherapy Rashes and Atopic Dermatitis

   • Dupilumab improves outcomes for immune checkpoint inhibitor rashes and shows no increase (possibly a decrease) in cardiometabolic risk, plus major psychiatric benefit in children

2. Biologic Switching in Plaque Psoriasis

   • Inter-class (IL-23 → IL-17 or vice versa) switch yields higher PASI90/100 rates than within-class switches
   • Hosts still prefer intra-class tries before changing mechanism unless high efficacy is needed

3. CRP as Biomarker in Adalimumab for HS

   • High CRP reflects more severe disease and predicts lower response odds but doesn’t mean no response; “still better to put them on adalimumab than placebo.” — Laura (50:26)

The Baby Three: Quick Studies

1. Gabapentin vs. Pregabalin for Pruritus

   • Both effective for itch, but gabapentin better tolerated; mirtazapine favored for elderly/side-effect sensitive patients due to lower fall risk
   • “I rarely use any of [the gabapentinoids] anymore because...increased hip fractures in elderly.” — Matt (52:10)

2. Lifetime Plaque Psoriasis Risk Following Guttate Flare

   • Only ~12.5% progress to chronic plaque; prior estimates were much higher
   • Reassurance: “80% chance this is going to be a one-time thing and go away.” — Matt (53:55)

3. Sterile vs. Non-sterile Gloves in Mohs Surgery

   • No infection rate difference; non-sterile gloves are 10x cheaper
   • “I am taking this data to my chair...I will be rich beyond my wildest dreams.” — Tim (55:28)

Trivia Section [39:05–41:52]

• Hawaii sunscreen ban year: Law passed 2018, effect 2021
• Finsen’s Nobel-winning TB treatment: Lupus vulgaris (cutaneous TB) with light radiation
• Origin of Coppertone: WWII Airman Benjamin Green invented it by mixing coconut oil/cocoa butter and petroleum

Timestamps for Key Segments

• Litfulo/Alopecia Areata Discussion: 01:43–06:28
• Baricitinib in Vitiligo: 06:37–10:40
• UV Exposure and Mortality: 10:40–16:20
• Deep Dive with Dr. Weller: 17:31–41:52
• Trivia: 39:05–41:52
• Little Three Articles: 41:58–51:03
• Baby Three Mini-Papers: 51:03–56:02

Closing Thoughts

The episode expertly balances emerging research, clinical pearls, and a touch of irreverence. The sun discussion is a standout, challenging dogma and urging a more nuanced, risk-based approach to UV exposure.

• “The message is for white Europeans...in a real high UV environment. It's not the same for everyone.” — Dr. Weller (35:51)
• “Don't get burned. Get sunshine.” — Dr. Weller (33:46)

Stay tuned for next week: Dr. Jakob Thyssen (Denmark) on novel eczema and hand dermatitis research.

For comments/suggestions:
Email: questions@dermsondrugs.com

Host Sign-Off:
“I hope you learned a few things, I hope you laughed a few times, and mostly I hope you plan to join us next week.” — Matt Zirwas (57:47)