Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1)
Background Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). Objectives The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to
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| Veröffentlicht in: | American journal of clinical dermatology 2020-04, Vol.21 (2), p.275-284 |
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| creator | Schlessinger, Joel Shepard, Julie S. Gower, Richard Su, John C. Lynde, Charles Cha, Amy Ports, William C. Purohit, Vivek Takiya, Liza Werth, John L. Zang, Chuanbo Vlahos, Bonnie |
| description | Background
Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).
Objectives
The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to |
| doi_str_mv | 10.1007/s40257-020-00510-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7125059</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2389239409</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-b869802e5b01ef1914928d016a66fcd9115da0ef0659e1169d4243c61cda84cb3</originalsourceid><addsrcrecordid>eNp9kcFuEzEQhlcIREvhBTggS1xAqmHs3XV2EUJapQEiJSqiwNXy2rOJy8YOtlOUG1fegqfgAXgUnoRNUwpcOIxmpPnn_0b6s-w-gycMYPQ0FsDLEQUOFKBkQMWN7JCxUU1ZVVU3L-eSQinYQXYnxnMYlBzE7ewg55xxBsVh9v1MdZi2x2TSdaiTvUCHMR4T5Qx5s1RhpbT_aB0mqyPxHRkHG1Xrg--RWEemrlMuRdIs0JCcJP_zy9fnQ_Hix7e5d2kZyWeblmRue0OTp3NvMKiEpEl-bTU5wYGQbLLxGWl2wIhk-oGcrtHRmWqxJ2dpY7bk0Y7bnCAZN28nhD2-m93qVB_x3lU_yt6_nLwbv6az01fTcTOjuhgVibaVqCvgWLbAsGM1K2peGWBCCdFpUzNWGgXYgShrZEzUpuBFrgXTRlWFbvOj7MXed71pV2g0uhRUL9fBrlTYSq-s_Hfj7FIu_IUcMV5CWQ8GD68Mgv-0wZjkud8EN_wseV7VPK8L2Kn4XqWDjzFgd01gIHdZy33WcshPXmYtxXD04O_frk9-hzsI8r0gDiu3wPCH_R_bX47fttE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2389239409</pqid></control><display><type>article</type><title>Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1)</title><source>MEDLINE</source><source>Springer Online Journals</source><creator>Schlessinger, Joel ; Shepard, Julie S. ; Gower, Richard ; Su, John C. ; Lynde, Charles ; Cha, Amy ; Ports, William C. ; Purohit, Vivek ; Takiya, Liza ; Werth, John L. ; Zang, Chuanbo ; Vlahos, Bonnie</creator><creatorcontrib>Schlessinger, Joel ; Shepard, Julie S. ; Gower, Richard ; Su, John C. ; Lynde, Charles ; Cha, Amy ; Ports, William C. ; Purohit, Vivek ; Takiya, Liza ; Werth, John L. ; Zang, Chuanbo ; Vlahos, Bonnie ; CARE 1 Investigators ; on behalf of the CARE 1 Investigators</creatorcontrib><description>Background
Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).
Objectives
The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study.
Methods
Infants (3 to < 24 months) with Investigator’s Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory).
Results
Included were 137 infants total (mean age [SD], 13.6 months [6.42]), with 21 in the PK cohort (12.7 months [6.58]). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was − 57.5%, and mean change in Patient-Oriented Eczema Measure total score was − 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years.
Conclusions
In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mild-to-moderate AD with systemic exposures similar to patients aged ≥ 2 years.
Clinical Trial Registration
NCT03356977.
Plain Language Summary
Atopic dermatitis (AD) is a skin disease that causes inflamed and itchy skin. Crisaborole is an ointment that is approved to treat patients aged 2 years and older with mild-to-moderate AD. This clinical trial studied crisaborole in infants with mild-to-moderate AD who were 3 to under 24 months old. These infants were treated with crisaborole twice a day for 28 days. The trial studied crisaborole’s safety, effectiveness, and absorption into the bloodstream. In total, 137 infants were treated. Although side effects of some sort occurred in about two-thirds of patients, only 1 in 6 patients experienced side effects that were attributed to crisaborole. When these side effects did occur, these were mainly pain, discomfort, or redness where crisaborole was applied. Fewer than 1 in 25 patients experienced each side effect where crisaborole was applied. The doctors saw improvement in the AD symptoms of some patients at day 29 of the study compared to the beginning of the study. Crisaborole blood-level measurements in this age group were consistent with those seen in patients aged 2 years and older. Overall, crisaborole was considered well tolerated and effective in infants (3 to under 24 months old) with mild-to-moderate AD.
Video abstract
ED1XZ2KJgk9TFtCNKJWX6P
Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: An Open-Label, Phase 4 Study (MP4 40891 MB)</description><identifier>ISSN: 1175-0561</identifier><identifier>EISSN: 1179-1888</identifier><identifier>DOI: 10.1007/s40257-020-00510-6</identifier><identifier>PMID: 32212104</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Antibiotics ; Babies ; Boron Compounds - adverse effects ; Boron Compounds - pharmacokinetics ; Bridged Bicyclo Compounds, Heterocyclic - adverse effects ; Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics ; Caregivers ; Dermatitis ; Dermatitis, Atopic - drug therapy ; Dermatology ; Drug dosages ; Eczema ; FDA approval ; Female ; Histamine ; Humans ; Infant ; Light therapy ; Male ; Medicine ; Medicine & Public Health ; NCT ; NCT03356977 ; Original ; Original Research Article ; Pain ; Pediatrics ; Pharmacokinetics ; Pharmacology/Toxicology ; Pharmacotherapy ; Phosphodiesterase 4 Inhibitors - adverse effects ; Phosphodiesterase 4 Inhibitors - pharmacokinetics ; Propylene Glycol - blood ; Treatment Outcome</subject><ispartof>American journal of clinical dermatology, 2020-04, Vol.21 (2), p.275-284</ispartof><rights>The Author(s) 2020</rights><rights>Copyright Springer Nature B.V. Apr 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-b869802e5b01ef1914928d016a66fcd9115da0ef0659e1169d4243c61cda84cb3</citedby><cites>FETCH-LOGICAL-c474t-b869802e5b01ef1914928d016a66fcd9115da0ef0659e1169d4243c61cda84cb3</cites><orcidid>0000-0002-4021-5423</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40257-020-00510-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40257-020-00510-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32212104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schlessinger, Joel</creatorcontrib><creatorcontrib>Shepard, Julie S.</creatorcontrib><creatorcontrib>Gower, Richard</creatorcontrib><creatorcontrib>Su, John C.</creatorcontrib><creatorcontrib>Lynde, Charles</creatorcontrib><creatorcontrib>Cha, Amy</creatorcontrib><creatorcontrib>Ports, William C.</creatorcontrib><creatorcontrib>Purohit, Vivek</creatorcontrib><creatorcontrib>Takiya, Liza</creatorcontrib><creatorcontrib>Werth, John L.</creatorcontrib><creatorcontrib>Zang, Chuanbo</creatorcontrib><creatorcontrib>Vlahos, Bonnie</creatorcontrib><creatorcontrib>CARE 1 Investigators</creatorcontrib><creatorcontrib>on behalf of the CARE 1 Investigators</creatorcontrib><title>Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1)</title><title>American journal of clinical dermatology</title><addtitle>Am J Clin Dermatol</addtitle><addtitle>Am J Clin Dermatol</addtitle><description>Background
Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).
Objectives
The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study.
Methods
Infants (3 to < 24 months) with Investigator’s Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory).
Results
Included were 137 infants total (mean age [SD], 13.6 months [6.42]), with 21 in the PK cohort (12.7 months [6.58]). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was − 57.5%, and mean change in Patient-Oriented Eczema Measure total score was − 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years.
Conclusions
In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mild-to-moderate AD with systemic exposures similar to patients aged ≥ 2 years.
Clinical Trial Registration
NCT03356977.
Plain Language Summary
Atopic dermatitis (AD) is a skin disease that causes inflamed and itchy skin. Crisaborole is an ointment that is approved to treat patients aged 2 years and older with mild-to-moderate AD. This clinical trial studied crisaborole in infants with mild-to-moderate AD who were 3 to under 24 months old. These infants were treated with crisaborole twice a day for 28 days. The trial studied crisaborole’s safety, effectiveness, and absorption into the bloodstream. In total, 137 infants were treated. Although side effects of some sort occurred in about two-thirds of patients, only 1 in 6 patients experienced side effects that were attributed to crisaborole. When these side effects did occur, these were mainly pain, discomfort, or redness where crisaborole was applied. Fewer than 1 in 25 patients experienced each side effect where crisaborole was applied. The doctors saw improvement in the AD symptoms of some patients at day 29 of the study compared to the beginning of the study. Crisaborole blood-level measurements in this age group were consistent with those seen in patients aged 2 years and older. Overall, crisaborole was considered well tolerated and effective in infants (3 to under 24 months old) with mild-to-moderate AD.
Video abstract
ED1XZ2KJgk9TFtCNKJWX6P
Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: An Open-Label, Phase 4 Study (MP4 40891 MB)</description><subject>Antibiotics</subject><subject>Babies</subject><subject>Boron Compounds - adverse effects</subject><subject>Boron Compounds - pharmacokinetics</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - adverse effects</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics</subject><subject>Caregivers</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - drug therapy</subject><subject>Dermatology</subject><subject>Drug dosages</subject><subject>Eczema</subject><subject>FDA approval</subject><subject>Female</subject><subject>Histamine</subject><subject>Humans</subject><subject>Infant</subject><subject>Light therapy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>NCT</subject><subject>NCT03356977</subject><subject>Original</subject><subject>Original Research Article</subject><subject>Pain</subject><subject>Pediatrics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Phosphodiesterase 4 Inhibitors - adverse effects</subject><subject>Phosphodiesterase 4 Inhibitors - pharmacokinetics</subject><subject>Propylene Glycol - blood</subject><subject>Treatment Outcome</subject><issn>1175-0561</issn><issn>1179-1888</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kcFuEzEQhlcIREvhBTggS1xAqmHs3XV2EUJapQEiJSqiwNXy2rOJy8YOtlOUG1fegqfgAXgUnoRNUwpcOIxmpPnn_0b6s-w-gycMYPQ0FsDLEQUOFKBkQMWN7JCxUU1ZVVU3L-eSQinYQXYnxnMYlBzE7ewg55xxBsVh9v1MdZi2x2TSdaiTvUCHMR4T5Qx5s1RhpbT_aB0mqyPxHRkHG1Xrg--RWEemrlMuRdIs0JCcJP_zy9fnQ_Hix7e5d2kZyWeblmRue0OTp3NvMKiEpEl-bTU5wYGQbLLxGWl2wIhk-oGcrtHRmWqxJ2dpY7bk0Y7bnCAZN28nhD2-m93qVB_x3lU_yt6_nLwbv6az01fTcTOjuhgVibaVqCvgWLbAsGM1K2peGWBCCdFpUzNWGgXYgShrZEzUpuBFrgXTRlWFbvOj7MXed71pV2g0uhRUL9fBrlTYSq-s_Hfj7FIu_IUcMV5CWQ8GD68Mgv-0wZjkud8EN_wseV7VPK8L2Kn4XqWDjzFgd01gIHdZy33WcshPXmYtxXD04O_frk9-hzsI8r0gDiu3wPCH_R_bX47fttE</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Schlessinger, Joel</creator><creator>Shepard, Julie S.</creator><creator>Gower, Richard</creator><creator>Su, John C.</creator><creator>Lynde, Charles</creator><creator>Cha, Amy</creator><creator>Ports, William C.</creator><creator>Purohit, Vivek</creator><creator>Takiya, Liza</creator><creator>Werth, John L.</creator><creator>Zang, Chuanbo</creator><creator>Vlahos, Bonnie</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4021-5423</orcidid></search><sort><creationdate>20200401</creationdate><title>Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1)</title><author>Schlessinger, Joel ; Shepard, Julie S. ; Gower, Richard ; Su, John C. ; Lynde, Charles ; Cha, Amy ; Ports, William C. ; Purohit, Vivek ; Takiya, Liza ; Werth, John L. ; Zang, Chuanbo ; Vlahos, Bonnie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-b869802e5b01ef1914928d016a66fcd9115da0ef0659e1169d4243c61cda84cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibiotics</topic><topic>Babies</topic><topic>Boron Compounds - adverse effects</topic><topic>Boron Compounds - pharmacokinetics</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - adverse effects</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics</topic><topic>Caregivers</topic><topic>Dermatitis</topic><topic>Dermatitis, Atopic - drug therapy</topic><topic>Dermatology</topic><topic>Drug dosages</topic><topic>Eczema</topic><topic>FDA approval</topic><topic>Female</topic><topic>Histamine</topic><topic>Humans</topic><topic>Infant</topic><topic>Light therapy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>NCT</topic><topic>NCT03356977</topic><topic>Original</topic><topic>Original Research Article</topic><topic>Pain</topic><topic>Pediatrics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Phosphodiesterase 4 Inhibitors - adverse effects</topic><topic>Phosphodiesterase 4 Inhibitors - pharmacokinetics</topic><topic>Propylene Glycol - blood</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schlessinger, Joel</creatorcontrib><creatorcontrib>Shepard, Julie S.</creatorcontrib><creatorcontrib>Gower, Richard</creatorcontrib><creatorcontrib>Su, John C.</creatorcontrib><creatorcontrib>Lynde, Charles</creatorcontrib><creatorcontrib>Cha, Amy</creatorcontrib><creatorcontrib>Ports, William C.</creatorcontrib><creatorcontrib>Purohit, Vivek</creatorcontrib><creatorcontrib>Takiya, Liza</creatorcontrib><creatorcontrib>Werth, John L.</creatorcontrib><creatorcontrib>Zang, Chuanbo</creatorcontrib><creatorcontrib>Vlahos, Bonnie</creatorcontrib><creatorcontrib>CARE 1 Investigators</creatorcontrib><creatorcontrib>on behalf of the CARE 1 Investigators</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of clinical dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schlessinger, Joel</au><au>Shepard, Julie S.</au><au>Gower, Richard</au><au>Su, John C.</au><au>Lynde, Charles</au><au>Cha, Amy</au><au>Ports, William C.</au><au>Purohit, Vivek</au><au>Takiya, Liza</au><au>Werth, John L.</au><au>Zang, Chuanbo</au><au>Vlahos, Bonnie</au><aucorp>CARE 1 Investigators</aucorp><aucorp>on behalf of the CARE 1 Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1)</atitle><jtitle>American journal of clinical dermatology</jtitle><stitle>Am J Clin Dermatol</stitle><addtitle>Am J Clin Dermatol</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>21</volume><issue>2</issue><spage>275</spage><epage>284</epage><pages>275-284</pages><issn>1175-0561</issn><eissn>1179-1888</eissn><abstract>Background
Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).
Objectives
The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study.
Methods
Infants (3 to < 24 months) with Investigator’s Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory).
Results
Included were 137 infants total (mean age [SD], 13.6 months [6.42]), with 21 in the PK cohort (12.7 months [6.58]). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was − 57.5%, and mean change in Patient-Oriented Eczema Measure total score was − 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years.
Conclusions
In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mild-to-moderate AD with systemic exposures similar to patients aged ≥ 2 years.
Clinical Trial Registration
NCT03356977.
Plain Language Summary
Atopic dermatitis (AD) is a skin disease that causes inflamed and itchy skin. Crisaborole is an ointment that is approved to treat patients aged 2 years and older with mild-to-moderate AD. This clinical trial studied crisaborole in infants with mild-to-moderate AD who were 3 to under 24 months old. These infants were treated with crisaborole twice a day for 28 days. The trial studied crisaborole’s safety, effectiveness, and absorption into the bloodstream. In total, 137 infants were treated. Although side effects of some sort occurred in about two-thirds of patients, only 1 in 6 patients experienced side effects that were attributed to crisaborole. When these side effects did occur, these were mainly pain, discomfort, or redness where crisaborole was applied. Fewer than 1 in 25 patients experienced each side effect where crisaborole was applied. The doctors saw improvement in the AD symptoms of some patients at day 29 of the study compared to the beginning of the study. Crisaborole blood-level measurements in this age group were consistent with those seen in patients aged 2 years and older. Overall, crisaborole was considered well tolerated and effective in infants (3 to under 24 months old) with mild-to-moderate AD.
Video abstract
ED1XZ2KJgk9TFtCNKJWX6P
Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: An Open-Label, Phase 4 Study (MP4 40891 MB)</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32212104</pmid><doi>10.1007/s40257-020-00510-6</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4021-5423</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1175-0561 |
| ispartof | American journal of clinical dermatology, 2020-04, Vol.21 (2), p.275-284 |
| issn | 1175-0561 1179-1888 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7125059 |
| source | MEDLINE; Springer Online Journals |
| subjects | Antibiotics Babies Boron Compounds - adverse effects Boron Compounds - pharmacokinetics Bridged Bicyclo Compounds, Heterocyclic - adverse effects Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics Caregivers Dermatitis Dermatitis, Atopic - drug therapy Dermatology Drug dosages Eczema FDA approval Female Histamine Humans Infant Light therapy Male Medicine Medicine & Public Health NCT NCT03356977 Original Original Research Article Pain Pediatrics Pharmacokinetics Pharmacology/Toxicology Pharmacotherapy Phosphodiesterase 4 Inhibitors - adverse effects Phosphodiesterase 4 Inhibitors - pharmacokinetics Propylene Glycol - blood Treatment Outcome |
| title | Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T17%3A47%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Safety,%20Effectiveness,%20and%20Pharmacokinetics%20of%20Crisaborole%20in%20Infants%20Aged%203%20to%E2%80%89%3C%E2%80%8924%C2%A0Months%20with%20Mild-to-Moderate%20Atopic%20Dermatitis:%20A%20Phase%20IV%20Open-Label%20Study%20(CrisADe%20CARE%201)&rft.jtitle=American%20journal%20of%20clinical%20dermatology&rft.au=Schlessinger,%20Joel&rft.aucorp=CARE%201%20Investigators&rft.date=2020-04-01&rft.volume=21&rft.issue=2&rft.spage=275&rft.epage=284&rft.pages=275-284&rft.issn=1175-0561&rft.eissn=1179-1888&rft_id=info:doi/10.1007/s40257-020-00510-6&rft_dat=%3Cproquest_pubme%3E2389239409%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2389239409&rft_id=info:pmid/32212104&rfr_iscdi=true |