From Black Box to Bargain Price: The Tofacitinib Comeback?

Summary

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Podcast Summary: Skin in the Game

Episode: From Black Box to Bargain Price: The Tofacitinib Comeback?
Hosts: Graham Lichman, DO, MS, FAAD & Diego Ruiz Da Silva, MD, FAAD
Date: August 3, 2026

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Episode Overview

This episode explores the past, present, and possible future of tofacitinib (an oral JAK inhibitor) as a therapy for atopic dermatitis (AD)—especially in the context of its new status as an inexpensive generic. The hosts discuss its initial promise, why it fell out of favor with the rise of selective JAK1 inhibitors and new safety data, and whether it might now have a renewed role for patients with limited access to newer, costlier therapies.

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Key Discussion Points & Insights

1. Actionable Clinical Pearls (00:52 – 01:47)

• Tofacitinib was never FDA-approved for atopic dermatitis:
  Early case reports showed rapid improvement in severe, treatment-resistant eczema with oral tofacitinib, despite its off-label status.

• Proof of concept for JAK inhibition:
  These early successes supported the idea that targeting the JAK-STAT pathway can dramatically improve AD, paving the way for today's JAK1-selective drugs.

• Affordable access with generics:
  Now that tofacitinib is available as a low-cost generic, it may have a place for select patients unable to access newer, expensive therapies.

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2. Historical Context: Where We Were & Where We're Going (01:47 – 03:59)

• Before Dupixent and modern JAKs:
  Treatment options (cyclosporine, methotrexate, prednisone, etc.) were limited and often unsatisfactory. Tofacitinib, first approved for rheumatoid arthritis, was considered for dermatology as it blocks inflammatory cytokines relevant in eczema and other immune-mediated diseases.

• Early clinical experience:

  • Initial studies were tiny (e.g., 6 patients), but showed promising efficacy (e.g., ~67% EASI improvement, 70% reduction in itch and sleep loss).

  • Tolerability was good—no infections, cytopenias, or concerning lab anomalies in these small series.

    “For 2015, those results were incredibly exciting...people are getting 70% better in multiple metrics.”
    — Graham (03:21)

• Mechanistic rationale:
  Tofacitinib inhibits multiple inflammatory pathways (IL-4, 13, 31, interferon gamma, IL-22, 17), offering broad immunomodulatory benefits—unlike therapies that hit a single cytokine.

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3. Why Did Dermatologists Move On? (03:59 – 05:07)

• Lack of large RCTs:
  Never developed in large phase 3 AD trials.

• Safer, more selective options emerged:
  Upadacitinib and abrocitinib (JAK1-selective) proved effective in robust studies and gained FDA approval.

• The “Black Box” era:
  The oral surveillance study attached serious infection, malignancy, and cardiovascular risk warnings to all oral JAK inhibitors—especially casting doubt on tofacitinib.

  “If that warning is...real at all, it’s real about Topha, but not necessarily the selective JAK1s.”
  — Diego (04:53)

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4. Tofacitinib’s Generic Comeback & Patient Access (05:07 – 07:51)

• Newly affordable:
  Now available as a generic for ~$30/month via cost-discount pharmacies (e.g., Mark Cuban’s Cost Plus Drugs).

• Renewed clinical relevance:
  May fill the gap for patients unable to secure insurance coverage or afford branded JAK inhibitors or biologics.

  “Could it be good enough for the patient who otherwise has no access to advanced therapy?”
  — Graham (06:05)

• Caveats:

  • Not a first-line or replacement for FDA-approved therapies where access/cost is similar.

  • Appropriate screening, monitoring, and risk counseling are essential—same as with other oral JAKs, possibly even more strictly.

    “We’re not saying that generic tofu should replace approved therapies…if cost and access are equal, I’m reaching for an FDA-approved medication every single time.”
    — Diego (06:26)

• Example monitoring protocol:

  • Baseline: CBC, CMP, Quantiferon Gold, HIV, hepatitis panel, lipids
  • 1 month: Repeat CBC, CMP, lipids
  • Every 3 months thereafter (more frequent than JAK1-selectives)

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5. Current Evidence & Clinical Scenarios (08:04 – 09:36)

• No large RCTs in AD:
  Only small case series and reports exist, with promising signals but nowhere near the evidence base of approved JAK1 inhibitors.

• Clinical role today:

  • Not used over FDA-approved options if both are accessible.

  • For patients with limited access to biologics/JAK1i, may be a justified option if fully informed of off-label status and adequately monitored.

    “If the patient had no access to any of these awesome therapies?...In carefully selected patients…it’s a great idea.”
    — Diego (09:25)

• Key advantage:
  Affordability for marginalized patients

• Key weakness:
  Limited high-quality, indication-specific data

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6. Personal Experiences & Practical Context (11:12 – 15:08)

• Host anecdotes:
  Both hosts have used oral tofacitinib, especially during training, for hard-to-treat pediatric cases (alopecia areata, eczema) and severe autoimmune or inflammatory dermatoses when nothing else was available.

  “The purpose it served was that the patients who were marginalized…for those patients, potentially it was a lifesaver.”
  — Graham (12:02)

• Recent cases:

  • Diego shares contemporary examples where tofacitinib was chosen due to lack of access to alternatives—e.g., refractory tumid lupus, severe esophageal lichen planus.

  • Reports “fantastic” results and minimal side effects historically, but always with rigorous monitoring.

    “Sometimes the most interesting drug isn’t the newest or shiniest one. It’s the one that everybody forgot about that you can get.”
    — Diego (10:24)

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7. Key Takeaway: It’s About Access, Not Efficacy (15:12 – 16:31)

• Primary question:
  Is this really an efficacy discussion or an access discussion?

  “You already know it, my friend. It’s 100% access discussion.”
  — Diego (16:10)

• Bottom line:

  • Use the best, FDA-approved therapy if available and affordable.
  • Tofacitinib’s renewed relevance is driven purely by access for disadvantaged patients, not superior efficacy.
  • Remain vigilant with counseling and monitoring for risks with its off-label use.

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Notable Quotes & Memorable Moments

• “I have zero hair. And it’s not because of my kids. It’s because of trying to get the dang access.”
  — Graham (05:16)

• “If, if we have equal access, we gotta go for the FDA approved therapies...but it’s reasonable to revisit Tofa if we need to for some patients.”
  — Diego (16:10)

• “We’re here to take the data, the ideas, the nuance—and make them more approachable, more usable…and ultimately more relevant to what actually happens in clinic.”
  — Show’s ethos

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Timestamps for Key Segments

• 00:52 – 01:47: “Three Pearls” actionable summary for the busy clinician
• 01:47 – 03:59: History and original use of tofacitinib in AD
• 03:59 – 05:07: Why dermatologists moved on from tofacitinib
• 05:07 – 07:51: Access, monitoring, and the generic comeback
• 08:04 – 09:36: Current evidence, patient suitability, treatment safety
• 11:12 – 15:08: Anecdotes, case experiences, and lessons from the past
• 15:12 – 16:31: Take-home: Access vs. efficacy debate

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Conclusion: Take-Home Message

Tofacitinib’s comeback is less about new science and more about old drugs finding new value due to changing economics. For the right patient—especially those struggling with modern medication access—the “forgotten” therapies may still have an important place. However, FDA-approved, data-rich options are preferred whenever possible.

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Hosts’ Closing Reminders:
Keep learning, keep questioning the evidence, and “keep your skin in the game.”

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Transcript

[A]

Hi, everyone. I'm Graham Lichman, practicing dermatologist and researcher at Vivita Dermatology in Las Vegas, Nevada.

[B]

And I'm Diego Ruiz da Silva, practicing at Forefront Dermatology in Virginia Beach.

[A]

And this is Skin in the Game. High yield dermatology. Quick hits for the busy clinician. Essentially, we read the research so you don't have to. Okay, today we're talking about a drug that most dermatologists probably haven't thought about for eczema in years. The drug is Tofacitinib. Okay, and then these articles that we're talking about today, there are two. One is from J.A.D. case reports by Shariari et al. Jack inhibitors as rescue therapy in depilumab refractory severe atopic dermatitis. And then also a JAD article from 2015, Levy et al. Treatment of recalcitrant atopic dermatitis with an oral Janus kinase inhibitor, Tofacitinib.

[B]

Nowadays, we have Renvoque Sibanco depiction, right? But before all of those, there was tofacitinib. And believe it or not, it helped lay the foundation for the entire JAK inhibitor era and atopic dermatitis, as well as many other inflammatory and autoimmune conditions. So three quick pearls here. Number one, oral tofacitinib was never FDA approved for atopic dermatitis. But early reports suggested rapid improvements in eczema and itch in patients who had failed multiple systemic therapies.

[A]

Okay. Number two, those early successes actually helped prove that blocking the JAK stat pathway could dramatically improve atop dermatitis. And this really sets the stage for today's approved JAK1 inhibitors.

[B]

And number three, now that generic tofacitinib is inexpensive, it's worth asking whether it still has a role for carefully selected patients who can't access newer therapies. Hence why we're talking about now after so long.

[A]

Okay, so we can't talk about where we are, where we're going, without talking about where we've been. So let's get to the history. Let's rewind to about 2015. Before Dupixent, before Nimluvio, before Adbury or Eblis, before Sinko or Rinvoq. Treatment options were, quite frankly, pretty depressing.

[B]

Yeah, we had cyclosporine, methotrexate, azathioprine, mycophenolate, a boatload of prednisone, and plenty of disappointed patients then came along. Tofacitinib.

[A]

Right.

[B]

Originally approved for rheumatoid arthritis. But people quickly started Asking if this blocks inflammatory cytokines in arthritis, could it work in eczema, alopecia, uh, you know, dermatomyositis, lupus, other conditions.

[A]

And with that question comes the clinical experience. Right. Finally, people are starting to use it. And so one of the first reports was tiny. Basically only six patients.

[B]

Small, but pretty fascinating. These were adult patients with moderate to severe atopic derm who had already failed multiple immunomodulatory therapies. Most receive oral tofacitinib 5mg twice a day after treatment. The average score at improved by nearly 55% within the first few months and ultimately improved by about 67% with continued therapy. Pruritus improved nearly 70% initially. Sleep loss improved by about the same, about 70. And those improvements were maintained. Perhaps most importantly, honestly, is that the drug was well tolerated in the small series. So no reported infection, cytopenias, liver toxicity, kidney dysfunction, lipid abnormalities. You know, kind of scary things that we worry about with Jax.

[A]

So, for 2015, those results were incredibly exciting. I mean, we're talking about something that's not showing huge safety signals, and people are getting 70% better in multiple metrics. So why did this drug seem to work so well?

[B]

It's because eczema is not driven by just one cytokine. Right. I think that's what's been hammered home now, in the era of the modern jaks, that we have, you know, Tovacid. And it blocks JAK signaling, which interrupts many of these inflammatory cytokines. So instead of just targeting one, you're dialing down on several. Right? You're getting 4, 1331 interfering gamma, IL22, IL17. There's more than just one thing we're getting.

[A]

I mean, that's a great point, but the thing is, we don't really use it today. So it begs the question, if it worked so well and was seemingly safe and hit all of these different pathways, why did everyone move on?

[B]

So, three reasons. Right. First, it was never formally developed through large phase 3 trials for AD. Second, newer JAK1 selective drugs like upadacitinib and Apricit that showed outstanding efficacy in much larger studies and ultimately gained FDA approval. And at that time, they were. They were phase two readouts, et cetera. Right? So people knew these things were coming. And third, the oral surveillance study really changed that conversation around JAK safety. Right. The box warning came with serious infections, malignancy, mace events, thrombosis, and it became part of every oral jack discussion, even, you know, JAK lovers. Like you and I, I think, shied away from Topacit at that point because we said, all right, if, if, if that warning is quote, unquote real at all, it's real about Topha, but not necessarily the selective JAK1s.

[A]

That's a great point, because both of us, you know, as we're speaking about JAK inhibitors, there's not a talk that goes by without us talking about the oral surveillance study. We're always referencing it. So again, it's like, why are we bringing up tophicitinib now?

[B]

The. The main reason is something's changed, right? It's no longer just an old branded drug. Generic topacity is now available, and that completely changes the game because of cost and access.

[A]

Wait, hold on a second. It's available now. I bet you some of you listening are going, what is he talking about available now? Well, here's the thing I have to say exactly, because. Because if you've prescribed Rinvoak or Sabinko recently, you know, access can be incredibly frustrating. This is probably one of the things that takes up most of our time. And anyone who knows me, I have zero hair. And it's not because of my kids. It's because of trying to get the dang access.

[B]

That's a great point, man. Meanwhile, generic immediate release Tofa can and extended release action can be purchased through pharmacies like Mark Cuban's cost plus drugs for a fraction of what the newer branded therapies cost, you know, about 30ish dollars a month. So the question becomes, not is it the best, Jack, but could it be good enough for the patient who otherwise has no access to advanced therapy?

[A]

So hearing this first, this is pretty exciting. But, you know, we actually need to be pretty careful here, because if we can get the absolute best and safest medication for a patient, that's what we should be doing at all times. But there are scenarios where that just can't happen. And so this is something to think about.

[B]

Yeah, I mean, we got to be careful, right?

[A]

Yeah.

[B]

We're not saying that generic tofu should replace approved therapies, right? In fact, if cost and access are equal, I'm reaching for an FDA approved medication every single time. Right? They have much larger efficacy data sets, longer follow up, substantially stronger evidence.

[A]

So now, so, you know, everyone listening is basically saying, so what the heck are we actually talking about? Diego?

[B]

I think this is the patient who's failed conventional systemic therapy, right? And someone who can't. Maybe it's one of those older immunosuppressants maybe it's just a bunch of systemic corticosteroids and topicals. And they can't obtain renvo, they can't get subanco, they can't afford a biologic. They don't, they don't qualify for any of these, you know, free or subsidized programs. And so they otherwise have very limited options. Right. For that patient, having an inexpensive oral jack becomes a very interesting discussion provided that they can understand that it's off label. Right. Limited ad specific evidence, and that the same screening, lab, monitoring, box warning counseling still applies. You know, we respect the medication and speaking of respecting the drug and the monitoring, you know, I figured we mentioned the, the monitoring I do at least oral tofacitinib, very similar to what I do for other oral jack inhibitors, but a little bit stricter. Right. So at baseline I check a, you know, cbc, cmp, quantiferian, gold, hiv, hepatitis panel, as well as lipids. And thereafter I'll check again in one month, just a cbc, a CMP and lipids. And then I'll check every three months thereafter those three basic labs. And you know, I think that's a little bit more aggressive than what I would typically do for an oral JAK1 inhibitor.

[A]

Right.

[B]

When I do my Rinvoc and Sabanco, I'll check labs baseline, I'll check labs at 12 weeks actually. And then thereafter, many patients I check, you know, once every six months or even once a year. It's actually pretty rare for me to check every three months.

[A]

So I think at this point, you know, everyone has their interest piqued. They're saying, okay, is tofa maybe a viable option? And maybe it is. But you all know on this podcast we love talking about the evidence. In fact, we, we like to dive in deep and make sure that you're not having to sift through it yourself. So let's make it easy for anyone. Ellie, Diego, has anyone done any large randomized trials with oral tofacitinib eczema specifically?

[B]

Nope, they have not, my friend. And any hope for that ever happening, you know, even before we had the official approved drugs, died with the box warning. Right? Now people want to stay away from it, but, but you know, there is this evidence that existed from before, right? So there's small case series, case reports, you know, so the signal is promising. It's just evidence doesn't simply compare with, with what we have for Yupa.

[A]

Okay, I mean, that's fair. So I, so I think at this point, let's just Go through some rapid fire. I think this was helpful last time. Hopefully people enjoy it. But what are we really getting out of this podcast? So first and foremost, most important contribution here from this paper.

[B]

So, so here I'd say it's, it's that Jack inhibition works in atopic dermatitis.

[A]

So would you choose it over invokes for instance, or Sabinko if insurance covered both?

[B]

Absolutely not. Right. So the evidence for approved therapies is far stronger and we're far, far safer being on label.

[A]

Ha.

[B]

Putt.

[A]

Would you consider it if the patient had no access to any of these awesome therapies?

[B]

Yeah, absolutely. So in carefully selected patient who understands it's off label and is willing to undergo appropriate monitoring. I think it's a great idea.

[A]

Okay, so what's the biggest advantage today for oral tofa?

[B]

So the biggest advantage is this affordability. Right. And its weakness is the limited evidence. But I think that there are a large number of patients who are willing to basically sacrifice this and understanding that it's similar enough to other medications that they can be monitored appropriately and then they don't have to pay hundreds or thousands of dollars for a drug that is very effective.

[A]

That's great. I love that. And so I, I think, you know, we don't have to belabor the point here. We can start to wrap this up. So really the take home message is, you know, today's episode isn't really about bringing back toacidmid.

[B]

Yeah. It's about recognizing where modern eczema therapy began. Right. And, and I think asking an important access question, could an inexpensive generic medication still have a place for the right patient?

[A]

The answer isn't yes for everyone and it certainly isn'. Therapy.

[B]

Yeah. But for the patients who can't afford. This conversation is worth having. And sometimes the most interesting drug isn't the newest or shiniest one. It's the one that everybody forgot about that you can get. Right. And I think this has come up recently and some of you guys who, who you know, kind of keep your ear to the ground in the literature or listen to other podcasts like Oral reflumelast has had a big buzz because it's, you know, it's also on the, the Mark Cuban's Cost plus pharmacy for cheap. And it's kind of become an alternative to a Tesla for lots of inflammatory conditions. And I remember first hearing about that in the last couple of years. And man, one day when tofacitinib's generic, like we're gonna have another fantastic option in the Same vein. Right. Graham, would you like to tell us, you know, some experiences I guess you had probably from the past. Right. When. When we didn't have anything else, using TOFA for AD or from or for any other inflammatory condition?

[A]

Yeah, so I haven't had the privilege of using it a bunch in my practice here in Vegas, but certainly in my training, we did have some opportunities to use that. Usually it was in a pediatric population. Difficult at the time to get anything else. We didn't really have anything approved. And so, you know, we go through. And based on tolerability, we'd see, you know, how the kids would take it for a number of different things. You know, not just eczema, but alopecia areata, some other chronic inflammatory diseases. And, you know, it was helpful for the most part. The purpose it served rather, was that the patients who were marginalized, who didn't have access or just didn't have approved treatment options, and for those patients, potentially it was a lifesaver.

[B]

Oh, and Graham, didn't you say that you had a patient recently, like an elderly gentleman with severe pemphigus foliatis you treated?

[A]

Yeah, that was a super tough case, and he was absolutely miserable. We had tried everything under the sun. We had gotten him a little bit better. At the end of the day, we had to just go back to the tried and true Imuran. And he had lots of GI side effects, but it's the only thing that could keep him down. But I wish I had known about something like oral tofu tofacitinib, and maybe that could have helped him.

[B]

So, Graham, my experience, honestly, is very similar to you from. From back in the day. As a resident. We use oral tofacinib a lot at the Children's Hospital. I was at CHOP in Philadelphia, and I trained with an awesome doc, Leslie Costello Sochio, who then went on to work at the NIH afterwards. But she was a alopecia areata expert at CHOP, MD, PhD, and had hundreds of kids on oral tofacitinib off label for alopecia areata, and kids from small little ones 4 or 5 years old, all the way up to teenagers 15, 16, 17, 18, and even some young adults who were under her care still. And I had this fantastic experience seeing these patients thrive, get all their hair back, do so safely, appropriate monitoring, very minimal side effects. And of course, this is before the box warning. And so I never thought anything bad of Jax. That's kind of how I was introduced to Jax, actually, as a. As a young med student. And then thereafter in residency, you know, also did quite a bit for autoimmune conditions for some refractory atopic dermatitis cases. Dr. Worth, who I trained with autoimmune conditions, I saw it used in some dermatomyositis and lupus patients. And so I had a fair bit of experience using it when necessary. So I, you know. But then, of course, I entered the world where we had approved therapies and kind of rarely got to think about this. But as this circled back around. Right. Being available cheaply and generically, I've actually used it in two patients recently. So I'm waiting to see them back, but I'm really excited to see how they do, because one was a patient I just diagnosed with tumid lupus. Significant edema, pain, inflammation of the lower face. Almost looks like angioedema. That's what she was told for a while because she would get episodes. But now it's been like six straight months of just edematous plaques of the lower face almost to a level where I thought it was in the sarcoid family or like a granulomas cheilitis type of issue. But biopsies were consistent with tumid lupus. And I just started her on hydroxychloroquine and oral tofacitinib to see if we can get this under control as fast as possible because she's miserable. And of course, as we talked about. Right. She was willing to accept, you know, moderate risk with appropriate monitoring, understanding this is off label and this is a tough autoimmune condition. And then I had a recent lichen planus, pretty severe cutaneous, like implanters. But. But more than that, esophageal, like implant is. Right. So GI actually sent her back to me and said, is there anything you can add on medically to try to help? Because I'm having to do dilations and there's a lot of inflammation in the esophagus. And I tried orinvoak and samples, and she didn't that much better. Marginal improvement. And that's. That's how I came upon. All right, let's do this tofacitin now that it's affordable. So, you know, keep you posted on the results there, Graham. But I'm excited to see how these patients do, and it was just nice to be able to offer hope with an oldie, but a goodie.

[A]

That's so great. Diego, I'm so glad that you shared that. Those are incredible examples, and I think it gives some pretty important context as to why all of us are obviously married to lifelong learning and why all of you guys are tuned in and continually trying to increase your knowledge and better yourselves and make yourselves the best possible clinicians you can be. I mean, Diego and I included, we're constantly learning, we're constantly being challenged. Why we love the field of dermatology. And so those are great things. I can't wait to hear all those patients are doing Diego. Hopefully we can bring bring that back into a future podcast. But I really want to end with something important because we talked about one this drug. Even though it's old, it's almost new again because now it's available and I have to say, Diego, tomorrow, generic hepatosidinib came out for 40 bucks a month. This episode never happens. So it really wants me to ask the question, is this really an efficacy discussion or is this just an access discussion?

[B]

You already know it, my friend. It's 100% access discussion. Right? If, if we have equal access, we gotta go for the FDA approved therapies, we gotta go for Renvoker Sabinko, because that's where the evidence is, you know, vastly stronger, particularly for ad. Right. But it's reasonable to revisit Tofa if we need to for some patients. And it's all about access and trying to take the best care of our patients.

[A]

Exactly. I love it. Thank you so much for listening, guys.

[B]

That's it for today's episode of Skin in the Game.

[A]

If you found this helpful, subscribe, leave us a review and share it with a colleague.

[B]

Until next time, keep questioning the evidence, keep learning, and keep your skin in the game.