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2yr
Safety of topical JAKi for atopic dermatitis

Atopic dermatitis (AD), also known as atopic eczema, is a chronic, pruritic, relapsing inflammatory dermatological condition. Treatment mainly aims at reducing itch and inflammation, eliminating flare-ups, and reducing side effects. Topical agents are considered as a primary treatment for mild-to-moderate AD and include topical corticosteroids, topical calcineurin inhibitors (TCI), topical phosphodiesterase 4 (PDE4) inhibitor crisaborole (Eucrisa), and more recently, the first topical Janus kinase (JAK) inhibitor, ruxolitinib cream 1.5% (Opzelura) approved for use in patients with mild-to-moderate AD.

In the topical ruxolitinib clinical studies, more than half of patients with mild-to-moderate AD achieved clear or almost clear skin as well as significant itch relief after 8 weeks. Nasopharyngitis was the most common AE experienced by 3% of patients vs 1% in control patients. Other AEs included diarrhea, bronchitis, ear infections, increase in eosinophil count, and hives, which occurred in 1% of ruxolitinib patients and less than 1% for control patients.

There is a black box warning on the label, which is primarily based on the oral JAKi, tafacitinib (Xeljanz, Pfizer). It is important to note that about 6% of topical ruxolitinib cream is absorbed into the bloodstream, a roughly 85% reduction from oral ruxolitinib.

What are your thoughts on the safety of a topical vs oral JAKi? What has been your experience with AEs from the topical therapies?

  • 2yr
    Topical nonsteroidal product under consideration, has been quite effective as an adjunctive therapy to injectable Dupixent and oral RinVoq. I have had good experience with both products. I have about 600 patients and Dupixent and with RinVoq less, but it was only approved in January of this year. It has been out now for 10 years and has five indications and is very effective in atopic dermatitis and especially in controlling itching. Main side effects have been upper respiratory and acne and cough. It’s rapid and durable. Well studied. 18 clinical trials on five different indications. Yes it has labs but any issues are transient and return to baseline and in the trials they have some of the worst possible patients. It is indicated for 12 and older, so I feel quite confident when you compare the data in the labs against the trials. I had one patient stop the oral, and it was upset stomach. It went away after discontinuation of the medicine.
  • 3yr
    Very beneficial that the topical route has a low systemic absorption rate as opposed to the oral method. I find it a challenge to prescribe the newer medication due to insurance restrictions and patient out of pocket costs despite being told it otherwise by the pharma company. For the select few that do take it, I have not seen or heard from patients on any of the AE mentioned
  • 3yr
    I have no problem with topical Opzelura. I have used in problematic Dupixent patients particularly on the face with excellent results. I know FDA copied oral safety issues to topical products without further information. I have no problem using topical products and have explained differences to patients. Patients are pleased with no burning and no steroid answer to medication need.
  • 3yr
    Even though there is minimal absorption, I have some concerns with immunosuppression. However, the risk of immunosuppression is significantly less than oral JAK inhibitors. I have limited experience with the topical JAK inhibitors, but thus far no significant adverse effects have been reported by my patients.
  • 3yr
    Regardless whether the JAK-i are oral and topical, they all have risk for developing serious infections that may lead to hospitalization or death, nonetheless the topical one may be used for mild to moderate atopic dermatitis.
  • 3yr
    Whether topical or systemic JAK-i work quickly to ease itching, inflammation, and other symptoms. With the topical agent, 6% being absorbed would make a difference as far as AE, concern about the effect on susceptibility to infection since it does lower your immune system’s power to fight infections as well as cancer risk
  • 3yr
    I am not concerned about the safety profile of the topical but would not use the oral. The only concern is the lack of insurance coverage which would make it financially difficult to use
  • 3yr
    I have no concerns (other than financial) over topical JAK inhibitors, and have prescribed it to several AD and vitiligo patients who have failed topical steroids (but I have not yet had an insurance company approve it). I have discussed oral JAK inhibitors with about a dozen patients; after reviewing the online information, all have declined.
  • 3yr
    I am unconcerned about the boxed warnings associated with topical JAK inhibitors. Opzelura works well, is safe and the warnings of oral JAK inh should not be in the same category as the topical JAK inh.
  • 3yr
    I consider as part of my step therapy topicals. If a patient has tried and failed TCS, TCI and still has localized areas amenable to topical therapy would consider topical JAK . Still consider this a short term as the data on combination use of topical with oral JAK or other biologics is lacking. However, nice to have a new effective topical.
  • 3yr
    since the dose exposure is much less than the oral form, i would imagine that it must be safer. however i will like to see more clinical safety data to feel completely confident in prescribing this new treatment. so far i have not seen any major adverse reactions from short term use. the results are actually quite good.
  • 3yr
    Topicals by nature have far fewer systemic effects and are, thus, safer. Starting with topicals makes sense with moving to systemics when topicals fail, especially in moderate cases.
  • 3yr
    I feel the topical therapy is extremely safe and effective with virtually no systemic adverse effects The oral systemic therapy has several black box warnings which require close monitoring of the patients but more highly effective therapy for patients with atopic dermatitis
  • 3yr
    I have no concerns with the safety for topical JAK inhibitors. I feel they are safer than systemic corticosteroids and have less side effects. I have had a degree of success with Opzelura cream, but it is not as effective as the oral JAK inhibitors.
  • 3yr
    The difference in systemic absorption between the oral and topical JAK inhibitors (85% vs. 6%) is significant and gives me much greater comfort in using Opzelura before its oral counterparts. Kind of analogous to the topical calcineurin inhibitors which most of us are now fairly comfortable prescribing regularly. Opzelura, Elidel, and Protopic all have black box warnings for malignancies, but the risks with their oral counterparts are much greater and broader. So far, no issues with tolerability of Opzelura among my patients.
  • 3yr
    Not an easy option for most patients, not to mention the coverage hurdles
  • 3yr
    Have not had anyone have any bad reactions to topical JAKI. For limited areas, this would be preferred to oral anyway. Orals may be more potent and more practical for more extensive cases, but the risk of adverse events / side effects is definitely higher with these orals.
  • 3yr
    I believe you have to look at alternatives other than the JAK inhibitors. For me oral steroid and immunosuppressants. The main side effects are obesity, glucose control, sodium and fluid retention in the steroid patients. So I think the issue should be in comparisone to steroid and immunosuppressants how do the side effects to JAKs hold up. For my patients that are diabetic, obese it stacks up very well.
  • 3yr
    Topical JAKs are definitely more safer and well tolerated. But as mentioned in previous comment should be used in limited quantity to prevent excess bloodstream absorption as this may cause more side effects.
  • 3yr
    In my experience they have been safe with minimal side effects!
  • 3yr
    I need to see more RWE with this class of antineoplastics being used for AD. Once I am comfortable the JAKI are safe for it, and see good efficacy, I will likely prescribe the class.
  • 3yr
    Regarding efficacy, topic JAKs may provide more of an immediate relief regarding symptoms but oral/systemic JAKs are more efficient in long term management, reducing exacerbations.
  • 3yr
    I agree with most of the previous comments. I feel that JAKs are generally safe when used in the right patient (non smoker, no cardiac risks etc.) Topical JAKs should be safer than oral JAKs. That said, there is absorption of topical rux. Therefore, one should be careful about the amount of BSA treated, especially if there is inflamed, broken skin which can lead to greater absorption.
  • 3yr
    As a Pediatric Oncologist and Pediatrician, this information makes me feel that Opzelura cream is reasonable to use after failing topical corticosteroid and moisturizer treatment. I cannot comment on use of oral Ruloxitinib for this indication.
  • 3yr
    It's difficult for family physicians to break into prescribing these meds because of insurance prior authorizations etc.. Even those of us who do a lot of care of the skin.
  • 3yr
    I would feel comfortable prescribing topical JAKi for patients who have not responsed to other treatments based on this data.
    Given the data on the oral versions and as a fanily practice provider, I feel it is unlikely I would initiate someone on that form.
  • 3yr
    I have had no safety issues to date with oral nor topical JAKi. This is very much in agreement with their data, where serious side effects are exceedingly rare. Based on my reading of the data, I think the warning for the topical JAKi is not consistent and overly aggressive when seen in the light of the actual safety data from the medicine's clinical studies. Nonetheless, since the warnings are present on the label I do feel obliged to address them with patients. During these discussions, I try to provide context about the meaning of the warnings and the infrequency or even rarity of serious side effects actually seen.
  • 3yr
    I agree with everyone; topical poses no problems except politically if you have to discuss the warning in the label; I choose the oral patients carefully, but it is somewhat easy since when you tell them about the warnings, they are either willing or not; also depending upon your explantions. Linda Susan Marcus
  • 3yr
    Regarding topical JAKS, I have no safety concerns since they are topical and at low risk of systemic absorption, and my patients seem to tolerate them well.
    I am more cautious about oral JAKS and their associated black box warnings, so I choose my patients carefully and avoid use in patients already at a higher risk for thrombosis or MACE. Have not seen any adverse events in any of my oral JAK patients.
    I have not found the topical JAKs to be overly effective at this point - maybe on par with mid potency topical steroids. But the oral JAKs - rinvoq in particular - have worked very well (and quickly) with sustained improvement in my moderate to severe AD patients who fail dupixent.
  • 3yr
    We are very selective about who gets prescribed a JAK inhibitors. So far the results have been great with no adverse reactions. This appears to be the new direction in treating AD
  • 3yr
    I have no concerns nor have any of my patients experienced AEs from topical JAK inhibitors. Due to the black box applied by the FDA, I do have concerns regarding the safety of the oral agents. I believe there are some issues underlying those studies ultimately leading to the black box warning that may have skewed results and perceptions. My experience has been that the TCIs were not potent enough to control most mild-moderate AD patients, one of the more recent entries into the topical AD market is poorly tolerated by many patients due to burning/stinging, which has limited it's use for me. The recently approved topical JAK has been very effective with no side effects in the patients I have used it. I plan to continue to incorporate it's use for many of those patients.

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