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Permalink Reply by tomasz777321 yesterday

"Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase."

- https://pubmed.ncbi.nlm.nih.gov/38391212/

"Baricitinib, a Janus kinase inhibitor, demonstrated efficacy in achieving scalp hair regrowth in severe alopecia areata (AA). While short-term real-world data on its efficacy have been reported, long-term data remain limited. This retrospective observational study spanning 104 weeks analyzed clinical trajectories of 51 severe AA patients treated with baricitinib. Among them, 36 continued treatment for 104 weeks, with 55.6% achieving a SALT score of ≤ 20 and 72.2% achieving ≥ 30% improvement from baseline in SALT score (SALT₃₀). Multivariate analysis identified female sex and disease duration < 4 years as significant predictors of response. Furthermore, patients with eyebrow or eyelash regrowth at 52 weeks had a higher likelihood of achieving long-term scalp hair regrowth. We identified a subgroup of markedly slow responders who achieved SALT₃₀ between 52 and 104 weeks, many of whom had eyebrow or eyelash regrowth at 52 weeks. Baricitinib was well tolerated throughout the study period, with no serious long-term adverse effects. Our findings supported baricitinib's long-term efficacy and safety and suggested predictive factors for treatment responses in severe AA.'

-https://pubmed.ncbi.nlm.nih.gov/40539396/

"LEQSELVI data presented at Fall Clinical includes pooled long-term results from open-label extension (OLE) studies showing ongoing and clinically meaningful improvements in scalp hair regrowth in adults with AA taking LEQSELVI for up to 68 weeks. To determine long-term efficacy, the Severity of Alopecia Tool (SALT) scores were analyzed using two methods: Last Observation Carried Forward (LOCF) and As Observed (AO). At the end of the qualifying trial period at Week 24, 32.6% of patients receiving LEQSELVI 8 mg BID (twice daily) achieved a SALT ≤20 score; the percentage of SALT 20 responders increased to 48.8% (LOCF analysis) and 76.6% (AO analysis) at Week 68 of the OLE studies. Additionally, 99.6% (282 patients) maintained their response to LEQSELVI 8 mg BID (as defined by sustaining a SALT ≤50 after achieving SALT ≤20 during the OLE studies as of the cutoff date)."

- https://www.prnewswire.com/news-releases/sun-pharma-presents-leqsel...

- https://www.dermatologytimes.com/view/long-term-results-demonstrate...

But this data is not comparable in my opinion because Lesqelvi uses LOCF and AO:

Last Observation Carried Forward (LOCF) is often criticized because it can artificially improve or “elevate” study results by making outcomes look more stable or favorable than they truly are. By simply repeating a participant’s last measured value, LOCF assumes that no further change occurred, which is rarely realistic especially in conditions that naturally worsen or fluctuate over time. For example, if patients drop out of a study because their condition is deteriorating, carrying forward their last (better) measurement can make a treatment appear more effective than it actually is. This approach also reduces variability in the data and can bias comparisons between groups, leading to overly optimistic conclusions. As a result, LOCF is generally considered a weak method for handling missing data in modern Statistical Analysis and is often replaced by more robust techniques that better reflect uncertainty and real-world changes.

As you can see in links earlier Leqselvi data is provided by SPONSOR and it uses LOCF so its less reliable than Olumiant which includend droput, Sponsor often uses  marketing, the data was from there:

"Sun Pharma Presents LEQSELVI™ (deuruxolitinib) Data Highlighting Clinical Efficacy & Durability for Treatment of Alopecia Areata at the 2024 Fall Clinical Dermatology Conference

As I mentioned earlier Olumiant I belive statistically provides quicker effects but the difference is marginal

Permalink Reply by nzahir yesterday

Well thats good to know, thanks for the data

I really only care about my eyebrows, eyelashes, and beard 

Looks like Olumiant can be better for this and quicker results, maybe, but not sure. But Leqselvi can be better for longer term due to the 2x a day and more stable exposure.

Does this seem accurate to you? Just wish I knew the reasoning behind why Olumi

If so, I would go with Olumiant if I can (insurance may be an issue though, so I will be looking into this)

I have thrown some questions and data into Chatgpt as well.

Eyebrow & Eyelash Data (what we have)

Olumiant (better documented)

In the BRAVE-AA trials:

• Eyebrow improvement (ClinRO scale):
  • ~35–38% achieved meaningful regrowth by week 36
• Eyelashes:
  • ~36–40% responders at week 36

👉 These are actually pretty strong relative to scalp response (~35%)

---

Leqselvi (more limited data)

From THRIVE-AA trials:

• Eyebrow/eyelash endpoints were reported, but:
  • Response rates were generally similar or slightly lower than scalp
  • Data is less emphasized and less consistent across releases

👉 Rough takeaway:

• ~25–35% range depending on endpoint and timepoint

---

🧠 Why would Olumiant do relatively better here?

This is where it gets interesting — it likely comes down to follicle biology + drug behavior, not just raw potency.

---

1. Eyebrow follicles are different

Eyebrow/eyelash follicles:

• Much shorter growth cycle
• More sensitive to immune signaling changes
• Less “deeply shut down” than scalp follicles in severe AA

So they may respond better to:

• faster-onset immune modulation

---

2. Olumiant has sharper peak activity

Compared to Leqselvi:

• Olumiant → higher peaks, shorter duration
• Leqselvi → more stable, flatter exposure

👉 Hypothesis:

• Peaks may trigger faster follicle reactivation
• Especially in smaller, more reactive follicles (like eyebrows)

---

3. Scalp vs face = different recovery problem

Area	What matters more
Scalp	sustained suppression over months
Eyebrows/eyelashes	rapid “kickstart” of follicles

So:

• Leqselvi advantage → long-term scalp recovery
• Olumiant advantage → quicker facial hair response

---

4. Clinical observation trend (2025–2026)

Dermatologists have noticed:

• Some patients on Olumiant regain eyebrows first, even if scalp lags
• Switching to Leqselvi sometimes improves scalp density later, not necessarily brows

This isn’t a formal rule — but it’s a pattern people are watching

---

⚖️ Practical takeaway

Goal	Drug that may have edge
Faster eyebrow/eyelash regrowth	Olumiant
Maximum long-term scalp coverage	Leqselvi
Simplicity / convenience	Olumiant

---

💡 Important caveat: There’s still no head-to-head trial, and eyebrow data for Leqselvi is less mature — so this is more of a directional insight than a proven superiority.

Why does OLumiant have "Faster immune suppression “kick”

Good question — this gets into pharmacokinetics + pharmacodynamics (how the drug moves through your body and how strongly it hits the target).

The reason Olumiant often has a faster “immune suppression kick” than Leqselvi comes down to a few key differences:

---

1) Faster rise to peak concentration (Cmax)

After you take a dose:

• Olumiant
  • Reaches peak blood levels in ~1–2 hours
  • Produces a relatively sharp spike
• Leqselvi
  • Also absorbed quickly, but designed to smooth out peaks
  • More gradual effective exposure over time

👉 That spike with Olumiant = stronger early JAK inhibition signal

---

2) Higher peak-to-trough swings

Think of it like this:

• Olumiant: “Spike → drop → spike → drop”
• Leqselvi: “Steady plateau”

That spike matters because:

• The autoimmune attack in Alopecia Areata is driven by cytokine bursts (like IFN-γ)
• A high peak drug level can shut that signaling down more abruptly

👉 Result: quicker interruption of the attack on hair follicles

---

3) Pharmacodynamic “threshold effect”

JAK inhibition isn’t linear — there’s a threshold effect:

• Below a certain level → immune system still active
• Above that level → signaling gets shut off quickly

Olumiant’s peak levels:

• Cross that threshold more decisively early on

Leqselvi:

• Crosses it too, but more gradually and consistently

---

4) Deuteration smooths Leqselvi (on purpose)

Leqselvi is deuterated, which:

• Slows metabolism
• Reduces fluctuations
• Extends exposure

That’s great for:

• Long-term suppression

But it reduces:

• sharp peak intensity

👉 So you trade:

• Speed (Olumiant) for
• Stability (Leqselvi)

---

5) Follicle biology amplifies this difference

Hair follicles in alopecia are:

• “stuck” in an immune attack state
• need a strong signal interruption to restart

A sharp inhibition (Olumiant):

• Can “flip the switch” faster → earlier regrowth

A steady inhibition (Leqselvi):

• Keeps them protected longer → more gradual but sustained recovery

---

🧠 Simple analogy

• Olumiant: like hitting a light switch hard → lights turn on quickly
• Leqselvi: like using a dimmer → slower ramp, but smoother and longer-lasting

---

⚖️ Big picture

Feature	Olumiant	Leqselvi
Peak intensity	Higher	Lower
Stability	Lower	Higher
Onset speed	Faster	Slower
Long-term durability	Moderate	Possibly higher

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