Derms on Drugs – "Drugs, Drugs and More Drugs"

Podcast: Derms on Drugs
Hosts: Dr. Matt Zirwas, Dr. Laura Ferris, Dr. Tim Patton
Episode Date: January 9, 2026

Episode Overview

This episode features another lively installment of the "six-pack" series, where the panel delivers rapid-fire analysis of some of the most intriguing dermatology studies and clinical trials from recent literature. As always, the trio blends actionable insights with humorous banter, dissecting topics ranging from new alopecia areata treatments and JAK inhibitor safety to comorbidities in hidradenitis suppurativa, updated NMSC risk data, and the efficacy of new topical agents.

Key Discussion Points & Insights

1. Duroxolitinib for Alopecia Areata (AA) – THRIVE-AA2 Phase 3 RCT

Lead Discussant: Dr. Laura Ferris
Timestamps: [01:06] – [11:27]

• Trial Overview: Phase 3 RCT comparing placebo to two doses (8mg and 12mg BID) of oral Duroxolitinib, a selective JAK1/2 inhibitor, in patients with moderate-severe AA.
• Mechanism: Similar to baricitinib; differs from ruxolitinib by deuteration (hydrogen replaced with deuterium), affecting PK and sidestepping patents ([02:14]).
• Inclusion Criteria & Outcomes:
  • Adults with ≥50% scalp hair loss (SALT ≥50), disease duration 6 months–10 years.
  • Measured % regrowth (SALT ≤20 & ≤10), patient satisfaction, safety.
• Key Results:
  • SALT ≤20 at 24 wks: 33% (8mg), 38% (12mg), 0.8% (placebo).
  • In most severe AA (≥95% loss), SALT ≤20: 20.9% (8mg), 26% (12mg), 0% (placebo).
  • SALT ≤10 (near-complete regrowth): ~25% (8 & 12mg), 0% (placebo).
  • No meaningful advantage to 12mg over 8mg.
• Patient-Reported:
  • ~50% “satisfied” or “very satisfied” with hair regrowth vs. <2% placebo.
• Safety:
  • High frequency of mild-moderate AEs (headache, nasopharyngitis, COVID, acne).
  • Main concern: DVT/PE events (>8mg) appeared in long-term extension, mostly among higher risk patients ([05:03], [13:50]).
• Meta-Analysis News: NMA showed Duroxolitinib 8mg BID consistently ranked best (~24 weeks) for high-level hair regrowth among approved JAKs ([11:27]).
• Prescribing Nuance:
  • Must test for CYP2C9 genotype before Rx, sim. to TPMT for azathioprine, due to metabolism variances linked with thrombotic risk ([12:24], [15:42]).
• Notable Quote:

  "The biggest difference... it got past the patent attorneys. But that deuterium in theory makes the half life different."
  — Dr. Zirwas ([02:25])

2. Comorbid Spondyloarthritis in Hidradenitis Suppurativa (HS)

Lead Discussant: Dr. Tim Patton
Timestamps: [16:05] – [22:43]

• Study: Cross-sectional analysis in Journal of Clinical Practice and Research, systematically screening 120 HS patients for SpA.
• Findings:
  • MRI-detected sacroiliitis: 13%, HLA-B27+: 12.5%
  • Peripheral SpA: 10%, Ankylosing spondylitis (New York criteria): 12.5%
  • Enthesitis: 18.3%
  • Severity of HS was not strongly tied to SpA risk.
• Clinical Implications:
  • HS patients should be screened for SpA.
  • May unlock access to more on-label therapies (e.g., OPA, Tofa, Ixekizumab).
• Practice Takeaway:

  “With a diagnosis of [SpA] in our HS patients, you could use on-label SpA meds... which could help treat the HS as well.”
  — Dr. Patton ([18:45])

3. JAK Inhibitors and Thrombosis Risk – Bench to Bedside

Lead Discussant: Dr. Matt Zirwas
Timestamps: [22:43] – [26:39]

• Bench Research: Some inflammatory diseases (psoriasis, HS, RA) have increased thrombosis risk due to IL-17A and TNF overexpression. JAK inhibitors don’t reverse this risk, whereas IL-17 and TNF inhibitors do ([24:00]).
• Lab Results:
  • Barry (baricitinib): lowest endothelial effect (possibly lowest thrombosis risk)
  • Rinvoq (upadacitinib): next best
  • Ruxolitinib: middle
  • Tofacitinib (Xeljanz): highest risk among tested JAKs.
• Disease Context Matters:
  • “In AD and AA... there shouldn’t be any risk of thrombosis from JAK inhibitors in those diseases. Mechanistically and data-wise.”
    — Dr. Zirwas ([25:40])
• Notable Moment:
  • Dr. Patton jokes about home endothelial cell testing:
    “I could do this in my kitchen.” ([26:16])

4. Socioeconomic Factors & Disease Course in HS

Lead Discussant: Dr. Matt Zirwas
Timestamps: [27:24] – [29:41]

• Study: 10-year follow-up, community-based Denmark cohort; reported 2/3 HS remission rate, only 1/6 progress, even among “severe” HS.
• Critique: Patient population not generalizable (homogenous, low BMI, universal healthcare, higher SES). Study failed to address these limitations in their conclusions.
• Notable Soapbox:

  “All of that is okay... except they never mention it. Drives me nuts because these journals hammer on socioeconomic and skin of color... and in the one study where it’s a huge factor, they didn’t mention it.”
  — Dr. Zirwas ([29:08])

5. Cryotherapy + Topical Tirbanibulin (“Klisyri”) for AK in Transplant Patients

Lead Discussant: Dr. Laura Ferris
Timestamps: [30:22] – [41:12]

• Design: Split-face RCT, 40 solid organ transplant recipients; compared cryo alone vs. cryo + topical Klisyri (turbanibulin) for actinic keratoses (AK).
• Results:
  • Superior clearance: 81% reduction (combo) vs. 53% (cryo alone); total clearance in 51% vs. 10%.
  • New AK formation also lowest in combo group.
• Side Effects: Mild-moderate, two SCCs (one each group).
• Practical Takeaway: Split-area design great for small, heterogenous pop; results support real-world regimen.
• Panel’s Go-To Regimen:
  • 5-FU + calcipotriene compounded (most evidence for reducing SCCs in this population, aligns w/ NCCN guidelines) ([39:36]–[40:03]).
• Entertaining Digression:
  • Long exchange on pronunciations: “tur-ban-i-bu-lin vs. turbi-nebulin”; “apoptosis vs. apoptosis” ([32:41]–[34:17])
• Notable Quote:

  “Treating AKs is basically cosmetic unless it reduces squames. So the fact that 5-FU and calcitri has data that it does that — other things don’t. That’s a big deal.”
  — Dr. Zirwas ([40:32])

6. Hydrochlorothiazide (HCTZ) and Skin Cancer: Large Korean Dataset

Lead Discussant: Dr. Tim Patton
Timestamps: [41:39] – [47:40]

• Study: >8,800 patients in HCTZ vs. non-HCTZ anti-HTN matched cohorts (from 11 Korean organizations).
• Result: No increased NMSC risk in HCTZ users; stable across subgroups (age, sex, duration).
• Controversy:
  • Global data inconsistent; FDA label warning exists, but absolute risk appears tiny.
  • Panel remains skeptical: likely only relevant in fair-skinned, high-UV-exposure populations ([44:23], [46:03]).
• Panel Wisdom:

  “I still think it matters, but... if you’re in a culture where you don’t sit outside in the sun all day, it probably doesn’t.”
  — Dr. Ferris ([46:07])

7. Minoxidil (Oral) + JAK Inhibitors for Severe Alopecia Areata

Lead Discussant: Dr. Zirwas
Timestamps: [47:40] – [50:16]

• Findings: Retrospective study (n=77) showed 50% of AT/AU patients reached SALT20 on combo baricitinib/minoxidil (median 2mg) at 12mo. (compared to ~20% with baricitinib alone).
• Practice Change: Dr. Zirwas now convinced: will recommend low-dose oral minoxidil alongside JAKs in AA.
• Safety: No need to routinely monitor BP, pulse, or labs for low-dose oral minoxidil.
• Notable Quote:

  “...It just seems like it grows hair. How’s it ever gonna hurt anything?”
  — Dr. Patton ([50:15])

8. Rocatinlimab (OX40 Blocker) for Moderate-Severe Atopic Dermatitis

Lead Discussant: Dr. Zirwas / Dr. Ferris
Timestamps: [50:18] – [53:29]

• Phase 3 Trials: Efficacy lower than existing biologics (easy75 ~50%, IGA 0/1 ~25% vs. 65–70% and 40% for dupilumab, lebrikizumab, etc.).
• Unique Side Effects: Some patients have fever/chills after 1st dose; some oral ulcers. Significance unclear.
• Future Hope: Could have immune “reset” effect—potential for durable remissions post-discontinuation.
• Mechanism/Immunology: OX40 blockade decreases effector T cells, rebalances Treg/Teff.
• Panel Caution: Too early to tell—efficacy may improve, but currently doesn’t unseat top agents.

Notable Quotes & Memorable Moments

• "The only difference, does it also give it more JAK1 selectivity? Did they tell you that?"
  — Dr. Ferris pushing for pharmacodynamic clarity ([02:59])
• "All I have to say, is I have a skincare routine to go over, I don't have time for all that nonsense. Nonsense."
  — Dr. Patton channeling HS comorbidity screening fatigue ([16:59])
• "No, it's like Denmark is the antithesis of North Carolina because nobody gets better here."
  — Dr. Ferris challenging HS remission rates ([29:41])
• "Bad doctor, not as bad doctor."
  — Dr. Ferris joking about their roles ([22:40])

Summary Table – Key Clinical Pearls

| Topic | Major Learning Point | |----------------------------|---------------------------------------------------------------------------------------------------------------------------| | Duroxolitinib for AA | 8mg BID offers strong efficacy w/ similar results to 12mg but lower thrombotic risk; test CYP2C9 first | | HS & Spondyloarthritis | Clinically significant comorbidity; may warrant more frequent screening/referral to rheum & impact Rx options | | JAK/Thrombosis Bench Data | Thrombosis risk difference among JAKs; disease context key; baricitinib lowest theoretical risk | | HS Remission Study Critique| Outcomes skewed by socioeconomic, ethnic, BMI factors; real world (esp US) patients very different | | AK in SOT Recipients | Cryo + tirbanibulin superior to cryo alone; 5-FU + calcipotriene remains gold standard for prevention of SCC | | HCTZ & NMSC Risk | New Korean data shows no increased risk; effect likely geography, UV, and skin-type dependent; minuscule absolute numbers | | Minoxidil + Baricitinib | Combo may be superior for severe AA variants; minimal risk, worth adding | | Rocatinlimab (OX40) | Lower efficacy vs. current AD biologics but possible future game-changer via immune resetting/remission potential |

Timestamps for Important Segments

• Duroxolitinib for AA: [01:06] – [11:27]
• HS & SpA: [16:05] – [22:43]
• JAKs, Thrombosis, Disease Context: [22:43] – [26:39]
• HS Remission Data Rant: [27:24] – [29:41]
• Cryo+Tirbanibulin for AK: [30:22] – [41:12]
• HCTZ & Skin Cancer Risk: [41:39] – [47:40]
• Minoxidil + Baricitinib in AA: [47:40] – [50:16]
• Rocatinlimab in AD: [50:18] – [53:29]

Conclusion

"Drugs, Drugs and More Drugs" highlights both new therapies and new questions for dermatology, all punctuated by the panel’s characteristic blend of skepticism, pragmatism, and wit. From the granular (how to pronounce “tirbanibulin”) to the global (generalizing clinical data across populations), listeners are invited to re-examine their routines, rethink where the evidence is strong (or not), and maybe even laugh—just a little—while keeping up with the field.