- Email: [email protected]
Lichen planus pigmentosus inversus: A case report of a rare entity
3232
3255
Ixekizumab, a novel antieIL-17A antibody, exhibits low immunogenicity during long-term treatment in patients with psoriasis Andrew Blauvelt, MD, MBA, Oregon Medical Research Center, Portland, OR, United States; Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Craig Leonardi, MD, Central Dermatology, St. Louis, MO, United States; Kenneth Gordon, MD, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Thomas Luger, MD, University of M€ unster, M€ unster, Germany; Mamitoro Ohtsuki, MD, PhD, Jichi Medical University, Shimotsuke, Japan; Brian Nickoloff, MD, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Lisa Kerr, MS, Eli Lilly and Company, Indianapolis, IN, United States; Gregory Cameron, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany Objectives: Anti-drug antibodies (ADA) can result in reduced biologic efficacy over time in patients (pts) with psoriasis. Here we evaluate treatment-emergent ADA (TEADA) to ixekizumab, an anti-IL-17A monoclonal antibody, for association with maintenance of efficacy and safety. Methods: The presence of ADAs was evaluated in pts from the induction period (012 weeks [wks]) of 3 randomized, controlled trials [RCTs] and the maintenance period (12-60 wks) of 2 of the 3 RCTs with the same randomized, blinded design. The induction period analyses included ADA-evaluable pts randomized to 80 mg ixekizumab either every 2 wks (IXE Q2W; N ¼ 1150) or 4 wks (IXE Q4W; N ¼ 1143) following a 160-mg starting dose. The maintenance period analyses included IXE responders at wk 12 who were rerandomized to IXE Q4W (N ¼ 397) or IXE Q12W (N ¼ 382). ADA serum trough levels were assessed using a highly drug-tolerant affinity capture elution screening assay. Results: Serum levels of TE-ADA were divided into negative, low, moderate, and high titer groups. At 12 wks, the vast majority of pts were TE-ADA negative (IXE Q2W: 91.0%; IXE Q4W: 86.6%). Additionally, among IXE Q2W and Q4W pts, respectively, 5.7% and 8.0% had low, 1.6% and 3.0% had moderate, and 1.7% and 2.4% had high TEADA titers at 12 wks. When evaluating efficacy during the induction period in pts receiving IXE Q2W, only pts with high TE-ADA titers had reduced responses in PASI compared to TE-ADA negative pts, with 12-wk mean percent improvement from baseline PASI (last observation carried forward [LOCF]) of 91.7%, 85.7%, 88.7%, and 53.5% for pts with negative, low, moderate, and high TE-ADA titer, respectively. The 12-wk PASI 75 response rates (nonresponder imputation) were 90.7%, 84.8%, 83.3%, and 36.8% for IXE Q2W pts with negative, low, moderate, and high TE-ADA titers, respectively. At 60 wks for IXE Q2W pts re-randomized to IXE Q4W during the maintenance period, 84.8% were TE-ADA negative, 14.2% had low, 0.9% had moderate, and none had high TE-ADA titer. Efficacy at 60 wks was similar between all TE-ADA groups with mean percent improvement from baseline PASI (LOCF) of 94.3% for negative, 97.0% for low, and 100% for moderate TE-ADA titer pts. IXE Q4W data was similar. No safety findings were correlated to ADA. Conclusions: TE-ADA levels against ixekizumab did not affect maintenance of response up to 60 wks among initial responders to ixekizumab. There was no correlation between TE-ADA and safety findings.
Lichen planus in a 12-year-old male with Noonan syndrome Lola Adekunle, Drexel Dermatology, Philadelphia, PA, United States; Chloe Etzler, MD, Drexel Dermatology, Philadelphia, PA, United States; Herbert Allen, MD, Drexel Dermatology, Philadelphia, PA, United States Lichen planus (LP) is a chronic inflammatory dermatosis of the skin and mucous membranes which is uncommon in children. We report a rare case of LP in a 12-yearold African American male with a history of Noonan syndrome (NS). Our patient presented with six months of extremely pruritic, flat-topped, purple-brown lesions involving his face and body. Histopathology revealed hyperkeratosis, hypergranulosis, a moderate irregular acanthosis, and a band-like infiltrate of lymphocytes and histiocytes in the upper dermis. Based on clinical and histopathologic findings, diagnosis was consistent with LP. The patient was treated with clobetasol 0.05% ointment and fluocinolone 0.025% cream with improvement. The classic presentation of LP features flat-topped, intensely pruritic, polygonal, violaceous papules and plaques with Wickham striae on flexural surfaces and mucous membranes. LP is uncommon in children, representing just 1-4% of cases. NS is an autosomal dominant genetic disorder involving the RAS-MAPK pathway that comprises characteristics such as short stature, facial dysmorphism, congenital heart defects, and learning disabilities. Dermatologic manifestations include woolly hair, abnormal pigmentation including multiple nevi, lentigines, and cafe au lait macules, and keratosis pilaris. There are no known reports of concurrent LP and Noonan syndrome. This case highlights the presentation of a common disease in an uncommon population. Commercial support: None identified.
Supported by Eli Lilly and Company.
3192 LAS41008 (dimethyl fumarate) improves health related quality of life and physician’s global assessment in the treatment of moderate to severe chronic plaque psoriasis: The BRIDGE study Ulrich Mrowietz, MD, Universit€atsklinikum Schleswig-Holstein, Kiel, Germany; Wolf-Godehard Ocker, MD, Almirall Hermal GmbH, Reinbek, Germany; Veronica Tebbs, MD, Island View Consulting, Nottingham, United Kingdom; Rosario Rodriguez, MD, Almirall SA, Barcelona, Spain; Rosa Lamarca, PhD, Almirall SA, Barcelona, Spain Introduction: Psoriasis is a debilitating disease; impairment of patient’s healthrelated quality of life (HrQoL) is comparable with that observed in other chronic conditions. HrQoL is a factor in the choice of medicinal product in clinical practice. Objective: To investigate safety, efficacy and impact on HrQoL of LAS41008 in the management of patients with moderate to severe chronic plaque psoriasis.
2929
Patients and methods: The efficacy, safety and effect on HrQoL of LAS41008 (dimethyl fumarate, DMF) were assessed in this 16-week, double-blind study. Patients were randomized to either LAS41008 (DMF), to LASW1835 (DMF and ethylhydrogenfumarate salts) or placebo in a 2:2:1 ratio, followed by a 52-week offtreatment period. The coprimary efficacy endpoints were clinical response by Physician’s Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI75) at week 16. Dermatology Life Quality Index (DLQI) at week 16 was a secondary endpoint. Treatment comparisons were based on P values from an asymptotic Wald test for risk difference. ANCOVA model was used for DLQI scores. Results: Overall, 671 patients were efficacy evaluable (267 LAS41008, 273 LASW1835 and 131 placebo). Mean age was 44.4 (SD ¼ 14.5) years and 64.7% were male. At baseline, around 60% of the patients had moderate PGA scores (PGA ¼ 3), mean PASI score was 16.3 (SD ¼ 6.0) and mean DLQI score 11.5 (SD ¼ 6.6). At week 16, a greater proportion of patients had clear/almost clear PGA scores on LAS41008 than placebo (33.0% vs 13.0%, respectively, P \.0001) and significantly better DLQI scores were reported in LAS41008-treated patients compared to placebo, 5.4 (SD ¼ 6.1) and 8.5 (SD ¼ 6.9), respectively (adjusted mean treatment difference of -3.23, P \.0001). Similarly with LASW1835, 37.4% were clear/almost clear (PGA). Mean DLQI score was 6.0 (SD ¼ 7.2). Conclusions: Study data show LAS41008 provides benefits in both HrQoL and PGA after 16 weeks in patients with moderate to severe chronic plaque psoriasis.
Lichen planus pigmentosus inversus: A case report of a rare entity Andrea Mabry, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Jay Kincannon, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Sarah Shalin, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Jerad Gardner, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States Case report: A 71-year-old woman presented with a 5-year history of progressive, asymptomatic erythematous hyperpigmented rash involving the intertriginous areas. She had no history of trauma to the areas of involvement. The patient was in good health, without a history of hepatitis or malignancy. Medications included bupropion, aspirin, and fluoxetine. Physical examination revealed annular violaceous to brown macules and patches with the long axis following the flexural fold and involving the inframammary chest, axillae, and gluteal cleft. Oral mucosa, hair, and nails were uninvolved. She had no other sites of skin involvement. Dermoscopic evaluation revealed diffuse erythematous brown patches containing multiple granular gray-brown dots and an overlying scale. Laboratory data, complete blood cell count, liver function tests, and electrolytes were within normal limits, including negative serologic tests for syphilis, HIV, hepatitis B and C viruses. Skin biopsies of the gluteal cleft revealed an atrophic epidermis, interface dermatitis with focal basal vacuolization, scattered dyskeratotic cells present along the dermoepidermal junction, marked pigment incontinence with melanophages in the papillary dermis. Topical calcineurin inhibitor therapy was initiated after the diagnosis of LPP inversus was made. Discussion: Lichen planus pigmentosus-inversus (LPP inversus) is a rare variant of lichen planus, with only 24 total cases reported in the medical literature. It presents as asymptomatic to mildly pruritic hyperpigmented macules and/or patches involving intertriginous and flexural areas and skin folds, most commonly the axilla and groin. The etiology of LPP inversus is thought to be T-cell mediated cytotoxic activity against basal keratinocytes. Treatment success with calcineurin inhibitors and high potency corticosteroids has been limited. Spontaneous regression has been documented. This represents a rare clinical variant of lichen planus.
Supported 100% by Almirall S.A.
Commercial support: None identified.
AB258
J AM ACAD DERMATOL
MAY 2016
3255
Ixekizumab, a novel antieIL-17A antibody, exhibits low immunogenicity during long-term treatment in patients with psoriasis Andrew Blauvelt, MD, MBA, Oregon Medical Research Center, Portland, OR, United States; Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Craig Leonardi, MD, Central Dermatology, St. Louis, MO, United States; Kenneth Gordon, MD, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Thomas Luger, MD, University of M€ unster, M€ unster, Germany; Mamitoro Ohtsuki, MD, PhD, Jichi Medical University, Shimotsuke, Japan; Brian Nickoloff, MD, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Lisa Kerr, MS, Eli Lilly and Company, Indianapolis, IN, United States; Gregory Cameron, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany Objectives: Anti-drug antibodies (ADA) can result in reduced biologic efficacy over time in patients (pts) with psoriasis. Here we evaluate treatment-emergent ADA (TEADA) to ixekizumab, an anti-IL-17A monoclonal antibody, for association with maintenance of efficacy and safety. Methods: The presence of ADAs was evaluated in pts from the induction period (012 weeks [wks]) of 3 randomized, controlled trials [RCTs] and the maintenance period (12-60 wks) of 2 of the 3 RCTs with the same randomized, blinded design. The induction period analyses included ADA-evaluable pts randomized to 80 mg ixekizumab either every 2 wks (IXE Q2W; N ¼ 1150) or 4 wks (IXE Q4W; N ¼ 1143) following a 160-mg starting dose. The maintenance period analyses included IXE responders at wk 12 who were rerandomized to IXE Q4W (N ¼ 397) or IXE Q12W (N ¼ 382). ADA serum trough levels were assessed using a highly drug-tolerant affinity capture elution screening assay. Results: Serum levels of TE-ADA were divided into negative, low, moderate, and high titer groups. At 12 wks, the vast majority of pts were TE-ADA negative (IXE Q2W: 91.0%; IXE Q4W: 86.6%). Additionally, among IXE Q2W and Q4W pts, respectively, 5.7% and 8.0% had low, 1.6% and 3.0% had moderate, and 1.7% and 2.4% had high TEADA titers at 12 wks. When evaluating efficacy during the induction period in pts receiving IXE Q2W, only pts with high TE-ADA titers had reduced responses in PASI compared to TE-ADA negative pts, with 12-wk mean percent improvement from baseline PASI (last observation carried forward [LOCF]) of 91.7%, 85.7%, 88.7%, and 53.5% for pts with negative, low, moderate, and high TE-ADA titer, respectively. The 12-wk PASI 75 response rates (nonresponder imputation) were 90.7%, 84.8%, 83.3%, and 36.8% for IXE Q2W pts with negative, low, moderate, and high TE-ADA titers, respectively. At 60 wks for IXE Q2W pts re-randomized to IXE Q4W during the maintenance period, 84.8% were TE-ADA negative, 14.2% had low, 0.9% had moderate, and none had high TE-ADA titer. Efficacy at 60 wks was similar between all TE-ADA groups with mean percent improvement from baseline PASI (LOCF) of 94.3% for negative, 97.0% for low, and 100% for moderate TE-ADA titer pts. IXE Q4W data was similar. No safety findings were correlated to ADA. Conclusions: TE-ADA levels against ixekizumab did not affect maintenance of response up to 60 wks among initial responders to ixekizumab. There was no correlation between TE-ADA and safety findings.
Lichen planus in a 12-year-old male with Noonan syndrome Lola Adekunle, Drexel Dermatology, Philadelphia, PA, United States; Chloe Etzler, MD, Drexel Dermatology, Philadelphia, PA, United States; Herbert Allen, MD, Drexel Dermatology, Philadelphia, PA, United States Lichen planus (LP) is a chronic inflammatory dermatosis of the skin and mucous membranes which is uncommon in children. We report a rare case of LP in a 12-yearold African American male with a history of Noonan syndrome (NS). Our patient presented with six months of extremely pruritic, flat-topped, purple-brown lesions involving his face and body. Histopathology revealed hyperkeratosis, hypergranulosis, a moderate irregular acanthosis, and a band-like infiltrate of lymphocytes and histiocytes in the upper dermis. Based on clinical and histopathologic findings, diagnosis was consistent with LP. The patient was treated with clobetasol 0.05% ointment and fluocinolone 0.025% cream with improvement. The classic presentation of LP features flat-topped, intensely pruritic, polygonal, violaceous papules and plaques with Wickham striae on flexural surfaces and mucous membranes. LP is uncommon in children, representing just 1-4% of cases. NS is an autosomal dominant genetic disorder involving the RAS-MAPK pathway that comprises characteristics such as short stature, facial dysmorphism, congenital heart defects, and learning disabilities. Dermatologic manifestations include woolly hair, abnormal pigmentation including multiple nevi, lentigines, and cafe au lait macules, and keratosis pilaris. There are no known reports of concurrent LP and Noonan syndrome. This case highlights the presentation of a common disease in an uncommon population. Commercial support: None identified.
Supported by Eli Lilly and Company.
3192 LAS41008 (dimethyl fumarate) improves health related quality of life and physician’s global assessment in the treatment of moderate to severe chronic plaque psoriasis: The BRIDGE study Ulrich Mrowietz, MD, Universit€atsklinikum Schleswig-Holstein, Kiel, Germany; Wolf-Godehard Ocker, MD, Almirall Hermal GmbH, Reinbek, Germany; Veronica Tebbs, MD, Island View Consulting, Nottingham, United Kingdom; Rosario Rodriguez, MD, Almirall SA, Barcelona, Spain; Rosa Lamarca, PhD, Almirall SA, Barcelona, Spain Introduction: Psoriasis is a debilitating disease; impairment of patient’s healthrelated quality of life (HrQoL) is comparable with that observed in other chronic conditions. HrQoL is a factor in the choice of medicinal product in clinical practice. Objective: To investigate safety, efficacy and impact on HrQoL of LAS41008 in the management of patients with moderate to severe chronic plaque psoriasis.
2929
Patients and methods: The efficacy, safety and effect on HrQoL of LAS41008 (dimethyl fumarate, DMF) were assessed in this 16-week, double-blind study. Patients were randomized to either LAS41008 (DMF), to LASW1835 (DMF and ethylhydrogenfumarate salts) or placebo in a 2:2:1 ratio, followed by a 52-week offtreatment period. The coprimary efficacy endpoints were clinical response by Physician’s Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI75) at week 16. Dermatology Life Quality Index (DLQI) at week 16 was a secondary endpoint. Treatment comparisons were based on P values from an asymptotic Wald test for risk difference. ANCOVA model was used for DLQI scores. Results: Overall, 671 patients were efficacy evaluable (267 LAS41008, 273 LASW1835 and 131 placebo). Mean age was 44.4 (SD ¼ 14.5) years and 64.7% were male. At baseline, around 60% of the patients had moderate PGA scores (PGA ¼ 3), mean PASI score was 16.3 (SD ¼ 6.0) and mean DLQI score 11.5 (SD ¼ 6.6). At week 16, a greater proportion of patients had clear/almost clear PGA scores on LAS41008 than placebo (33.0% vs 13.0%, respectively, P \.0001) and significantly better DLQI scores were reported in LAS41008-treated patients compared to placebo, 5.4 (SD ¼ 6.1) and 8.5 (SD ¼ 6.9), respectively (adjusted mean treatment difference of -3.23, P \.0001). Similarly with LASW1835, 37.4% were clear/almost clear (PGA). Mean DLQI score was 6.0 (SD ¼ 7.2). Conclusions: Study data show LAS41008 provides benefits in both HrQoL and PGA after 16 weeks in patients with moderate to severe chronic plaque psoriasis.
Lichen planus pigmentosus inversus: A case report of a rare entity Andrea Mabry, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Jay Kincannon, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Sarah Shalin, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Jerad Gardner, MD, University of Arkansas for Medical Sciences, Little Rock, AR, United States Case report: A 71-year-old woman presented with a 5-year history of progressive, asymptomatic erythematous hyperpigmented rash involving the intertriginous areas. She had no history of trauma to the areas of involvement. The patient was in good health, without a history of hepatitis or malignancy. Medications included bupropion, aspirin, and fluoxetine. Physical examination revealed annular violaceous to brown macules and patches with the long axis following the flexural fold and involving the inframammary chest, axillae, and gluteal cleft. Oral mucosa, hair, and nails were uninvolved. She had no other sites of skin involvement. Dermoscopic evaluation revealed diffuse erythematous brown patches containing multiple granular gray-brown dots and an overlying scale. Laboratory data, complete blood cell count, liver function tests, and electrolytes were within normal limits, including negative serologic tests for syphilis, HIV, hepatitis B and C viruses. Skin biopsies of the gluteal cleft revealed an atrophic epidermis, interface dermatitis with focal basal vacuolization, scattered dyskeratotic cells present along the dermoepidermal junction, marked pigment incontinence with melanophages in the papillary dermis. Topical calcineurin inhibitor therapy was initiated after the diagnosis of LPP inversus was made. Discussion: Lichen planus pigmentosus-inversus (LPP inversus) is a rare variant of lichen planus, with only 24 total cases reported in the medical literature. It presents as asymptomatic to mildly pruritic hyperpigmented macules and/or patches involving intertriginous and flexural areas and skin folds, most commonly the axilla and groin. The etiology of LPP inversus is thought to be T-cell mediated cytotoxic activity against basal keratinocytes. Treatment success with calcineurin inhibitors and high potency corticosteroids has been limited. Spontaneous regression has been documented. This represents a rare clinical variant of lichen planus.
Supported 100% by Almirall S.A.
Commercial support: None identified.
AB258
J AM ACAD DERMATOL
MAY 2016