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SAN DIEGO — , according to late breaker data presented at the annual meeting of the American Academy of Dermatology.
Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to Rodney D. Sinclair, MD, professor of dermatology at the University of Melbourne, Australia.
His remarks were derived specifically from new long-term follow-up with baricitinib, the first JAK inhibitor approved for AA, but the pattern appears to be similar with ritlecitinib, the only other JAK inhibitor approved for AA, and for several if not all JAK inhibitors in phase 3 AA trials.
“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported
A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.
Providing the most recent analysis in patients with severe AA participating in the phase 3 BRAVE-AA1 and BRAVE-AA2 trials of baricitinib, which were published together in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied.
In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups.
Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks.
Response Curves Climb More Slowly With Severe Alopecia
While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76.
The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small.
Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.
Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration.
“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.
To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said.
The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.
This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration ALLEGRO trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a summary published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.
In the context of late breaking 68-week data with deuruxolitinib, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.
The difference between AA and most other inflammatory conditions treated with a JAK inhibitor is that “it takes time to treat,” Dr. King said.
Time Factor Is Important for Response
“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.
“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”
Asked to comment, Melissa Piliang, MD, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.
“In my clinical experience, 6 months is not long enough to assess response,” she told this news organization. “Some patients have hair growth after 18 months to 2 years” of treatment. Additional studies to identify the characteristics and predictors of late response, she said, “would be very helpful, as would trials allowing multiple therapies to simulate real-world practice.”
Like Dr. Sinclair, Dr. Piliang is interested in the possibility of combining a JAK inhibitor with another therapy aimed specially at promoting hair regrowth.
“Using a secondary therapy to stimulate regrowth as an addition to an anti-inflammatory medicine like a JAK inhibitor might speed up response in some patients,” she speculated. Dr. Sinclair reports financial relationships with more than 30 pharmaceutical companies, including Eli Lilly, the manufacturer of baricitinib. Dr. King reports financial relationships with multiple companies, including Concert Pharmaceuticals (consultant and investigator), the manufacturer of deuruxolitinib. Dr. Piliang reports financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble.
SAN DIEGO — , according to late breaker data presented at the annual meeting of the American Academy of Dermatology.
Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to Rodney D. Sinclair, MD, professor of dermatology at the University of Melbourne, Australia.
His remarks were derived specifically from new long-term follow-up with baricitinib, the first JAK inhibitor approved for AA, but the pattern appears to be similar with ritlecitinib, the only other JAK inhibitor approved for AA, and for several if not all JAK inhibitors in phase 3 AA trials.
“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported
A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.
Providing the most recent analysis in patients with severe AA participating in the phase 3 BRAVE-AA1 and BRAVE-AA2 trials of baricitinib, which were published together in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied.
In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups.
Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks.
Response Curves Climb More Slowly With Severe Alopecia
While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76.
The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small.
Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.
Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration.
“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.
To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said.
The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.
This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration ALLEGRO trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a summary published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.
In the context of late breaking 68-week data with deuruxolitinib, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.
The difference between AA and most other inflammatory conditions treated with a JAK inhibitor is that “it takes time to treat,” Dr. King said.
Time Factor Is Important for Response
“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.
“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”
Asked to comment, Melissa Piliang, MD, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.
“In my clinical experience, 6 months is not long enough to assess response,” she told this news organization. “Some patients have hair growth after 18 months to 2 years” of treatment. Additional studies to identify the characteristics and predictors of late response, she said, “would be very helpful, as would trials allowing multiple therapies to simulate real-world practice.”
Like Dr. Sinclair, Dr. Piliang is interested in the possibility of combining a JAK inhibitor with another therapy aimed specially at promoting hair regrowth.
“Using a secondary therapy to stimulate regrowth as an addition to an anti-inflammatory medicine like a JAK inhibitor might speed up response in some patients,” she speculated. Dr. Sinclair reports financial relationships with more than 30 pharmaceutical companies, including Eli Lilly, the manufacturer of baricitinib. Dr. King reports financial relationships with multiple companies, including Concert Pharmaceuticals (consultant and investigator), the manufacturer of deuruxolitinib. Dr. Piliang reports financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble.
SAN DIEGO — , according to late breaker data presented at the annual meeting of the American Academy of Dermatology.
Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to Rodney D. Sinclair, MD, professor of dermatology at the University of Melbourne, Australia.
His remarks were derived specifically from new long-term follow-up with baricitinib, the first JAK inhibitor approved for AA, but the pattern appears to be similar with ritlecitinib, the only other JAK inhibitor approved for AA, and for several if not all JAK inhibitors in phase 3 AA trials.
“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported
A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.
Providing the most recent analysis in patients with severe AA participating in the phase 3 BRAVE-AA1 and BRAVE-AA2 trials of baricitinib, which were published together in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied.
In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups.
Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks.
Response Curves Climb More Slowly With Severe Alopecia
While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76.
The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small.
Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.
Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration.
“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.
To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said.
The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.
This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration ALLEGRO trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a summary published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.
In the context of late breaking 68-week data with deuruxolitinib, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.
The difference between AA and most other inflammatory conditions treated with a JAK inhibitor is that “it takes time to treat,” Dr. King said.
Time Factor Is Important for Response
“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.
“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”
Asked to comment, Melissa Piliang, MD, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.
“In my clinical experience, 6 months is not long enough to assess response,” she told this news organization. “Some patients have hair growth after 18 months to 2 years” of treatment. Additional studies to identify the characteristics and predictors of late response, she said, “would be very helpful, as would trials allowing multiple therapies to simulate real-world practice.”
Like Dr. Sinclair, Dr. Piliang is interested in the possibility of combining a JAK inhibitor with another therapy aimed specially at promoting hair regrowth.
“Using a secondary therapy to stimulate regrowth as an addition to an anti-inflammatory medicine like a JAK inhibitor might speed up response in some patients,” she speculated. Dr. Sinclair reports financial relationships with more than 30 pharmaceutical companies, including Eli Lilly, the manufacturer of baricitinib. Dr. King reports financial relationships with multiple companies, including Concert Pharmaceuticals (consultant and investigator), the manufacturer of deuruxolitinib. Dr. Piliang reports financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167622</fileName> <TBEID>0C04F75C.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F75C</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>Long-term JAKi for Alopecia</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240412T115533</QCDate> <firstPublished>20240412T120100</firstPublished> <LastPublished>20240412T120100</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240412T120059</CMSDate> <articleSource>FROM AAD 2024 </articleSource> <facebookInfo/> <meetingNumber>2884-24</meetingNumber> <byline>Ted Bosworth</byline> <bylineText>TED BOSWORTH</bylineText> <bylineFull>TED BOSWORTH</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>In patients with alopecia areata (AA), the decision of when to give up on JAK inhibitors because of an inadequate response is being complicated by long-term fol</metaDescription> <articlePDF/> <teaserImage>301114</teaserImage> <teaser>Delayed but clinically significant responses are seen a year or more after starting JAK inhibitors for alopecia areata. </teaser> <title>Alopecia Areata: Late Responses Complicate Definition of JAK Inhibitor Failure</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>skin</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">13</term> </publications> <sections> <term>53</term> <term canonical="true">39313</term> </sections> <topics> <term canonical="true">219</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012820.jpg</altRep> <description role="drol:caption">Dr. Brett King</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012821.jpg</altRep> <description role="drol:caption">Dr. Melissa Piliang</description> <description role="drol:credit">Dr. Piliang</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Alopecia Areata: Late Responses Complicate Definition of JAK Inhibitor Failure</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">SAN DIEGO</span> — <span class="tag metaDescription"> In patients with alopecia areata (AA), the decision of when to give up on JAK inhibitors because of an inadequate response is being complicated by long-term follow-up showing that some patients accrue hair very slowly</span>, according to late breaker data presented at the annual meeting of the American Academy of Dermatology.</p> <p>Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to <span class="Hyperlink"><a href="https://findanexpert.unimelb.edu.au/profile/2015-rodney-sinclair">Rodney D. Sinclair, MD</a></span>, professor of dermatology at the University of Melbourne, Australia.<br/><br/>His remarks were derived specifically from new long-term follow-up with <span class="Hyperlink"><a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s007lbl.pdf">baricitinib</a></span>, the first JAK inhibitor <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/975487">approved for AA</a></span>, but the pattern appears to be similar with <span class="Hyperlink"><a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215830s000lbl.pdf">ritlecitinib</a></span>, the only other JAK inhibitor <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/993663">approved for AA</a></span>, and for several if not all JAK inhibitors in phase 3 AA trials.<br/><br/>“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported <br/><br/>A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.<br/><br/>Providing the most recent analysis in patients with severe AA participating in the phase 3 <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT03570749">BRAVE-AA1</a></span> and <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT03899259">BRAVE-AA2</a></span> trials of baricitinib, which were <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2110343">published together</a></span> in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied. <br/><br/>In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups. <br/><br/>Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks. <br/><br/><br/><br/></p> <h2>Response Curves Climb More Slowly With Severe Alopecia</h2> <p>While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76. </p> <p>The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small. <br/><br/>Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.<br/><br/>Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration. <br/><br/>“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.<br/><br/>To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said. <br/><br/>The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.<br/><br/>This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT03732807?term=NCT03732807&rank=1&tab=results">ALLEGRO</a></span> trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a <span class="Hyperlink"><a href="https://link.springer.com/article/10.1007/s40265-023-01928-y">summary</a></span> published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.<br/><br/>In the context of late breaking 68-week data with <span class="Hyperlink">deuruxolitinib</span>, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, <span class="Hyperlink"><a href="https://medicine.yale.edu/profile/brett-king/">Brett King, MD, PhD</a></span>, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.[[{"fid":"301114","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Brett King, Yale University School of Medicine, New Haven, CT","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Brett King"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>The difference between AA and most other inflammatory conditions treated with a JAK inhibitor is that “it takes time to treat,” Dr. King said. <br/><br/><br/><br/></p> <h2>Time Factor Is Important for Response</h2> <p>“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.</p> <p>“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”<br/><br/>Asked to comment, <span class="Hyperlink"><a href="https://my.clevelandclinic.org/staff/7887-melissa-piliang">Melissa Piliang, MD</a></span>, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.[[{"fid":"301115","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Melissa Piliang, MD, Chair of Dermatology at the Cleveland Clinic, Cleveland, Ohio","field_file_image_credit[und][0][value]":"Dr. Piliang","field_file_image_caption[und][0][value]":"Dr. Melissa Piliang"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>“In my clinical experience, 6 months is not long enough to assess response,” she told this news organization. “Some patients have hair growth after 18 months to 2 years” of treatment. Additional studies to identify the characteristics and predictors of late response, she said, “would be very helpful, as would trials allowing multiple therapies to simulate real-world practice.”<br/><br/>Like Dr. Sinclair, Dr. Piliang is interested in the possibility of combining a JAK inhibitor with another therapy aimed specially at promoting hair regrowth.<br/><br/>“Using a secondary therapy to stimulate regrowth as an addition to an anti-inflammatory medicine like a JAK inhibitor might speed up response in some patients,” she speculated. Dr. Sinclair reports financial relationships with more than 30 pharmaceutical companies, including Eli Lilly, the manufacturer of baricitinib. Dr. King reports financial relationships with multiple companies, including Concert Pharmaceuticals (consultant and investigator), the manufacturer of deuruxolitinib. Dr. Piliang reports financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM AAD 2024
