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Lichen planus along the lines of Blaschko
P2747
P2749
PASI-100 is associated with better dermatology-specific patient reported outcomes compared with PASI-75e99: Subanalysis of a phase II psoriasis trial of adalimumab Kenneth Gordon, MD, Dermatology, Evanston Northwestern Healthcare, Skokie, IL, United States; Alexa Kimball, MD, MPH, Massachusetts General and Brigham and Women’s Hospitals, Harvard Medical School, Boston, MA, United States; Richard Langley, MD, Dalhousie University, Halifax, NS, Canada; Martin Okun, MD, PhD, Abbott Laboratories, Abbott Park, IL, United States
Lichen planus along the lines of Blaschko Manjeet Mehmi, MBChB, Birmingham Skin Centre, Birmingham, United Kingdom; Periasamy Balasubramaniam, MBBS, MD, Birmingham Skin Centre, Birmingham, United Kingdom; Virginia Hill, MD, Birmingham Children’s Hospital, Birmingham, United Kingdom
Objective: To determine whether the difference between PASI-100 and PASI-75e99 is clinically meaningful, as assessed by patient reported outcomes in adalimumabtreated patients. Methods: Randomized treatment arms included: 1) placebo (n = 52); 2) adalimumab 80 mg subcutaneously (sc) at week 0, then adalimumab 40 mg sc every other week (eow) starting at week 1 (n = 45); and 3) adalimumab 80 mg sc at weeks 0 and 1, then adalimumab 40 mg sc weekly starting at week 2 (n = 50). At week 12, placebo patients were switched to adalimumab 40 mg eow (placebo/adalimumab eow). Skin (PASI) and patient reported outcomes (DLQI) were assessed up to week 60. Results: At week 60, PASI-75e99/100 response ratios were 38%/17% for the placebo/adalimumab eow 1 adalimumab eow group and 38%/26% for the adalimumab weekly group (observed analysis). Pooling patients with similar percentage PASI improvement across treatment arms, patients with PASI \50 (n = 5), 50e74 (n = 18), 75e99 (n = 54), and 100 (n = 29) at week 60 had mean DLQI scores (lower score indicates better health status) of 3.0, 3.3, 1.8, and 0.3, respectively. Mean reductions from baseline in DLQI were 6.0, 8.8, 11.5, and 11.1, respectively (MCID estimated at 5.7). At week 60, 0%/28%/37%/79% of patients with PASI \50/50e74/75e99/100 had a DLQI score of 0, respectively, 20%/17%/35%/10% had a DLQI score of 1, respectively, 40%/17%/7%/10% had a DLQI score of 2, respectively, and 40%/39%/20%/0% had a DLQI score of $3, respectively.
A 14-year-old boy with a 12-year history of atopic dermatitis presented with a 2-month history of a lichenoid eruption on the forearm and shins, also occurring in a blaschkoid pattern on the left side of his abdomen. A skin biopsy revealed histological features of lichen planus (LP). There was no previous history of hepatitis B or C. The LP responded well to twice daily moderate potency topical steroid application over the course of 3 months. Of all LP patients, 0.24-0.62% display the linear LP variant. Linear LP usually occurs in strips or segments of skin larger than can be explained solely by the Koebner phenomenon. Multiple lesions can be seen in a pattern previously described as zosteriform. Only a few cases have been described occurring along Blaschko’s lines. Blaschko’s lines were first described in 1901. Lesions following Blaschko’s lines present with a characteristic V-shape near the posterior midline, linear pattern on the trunk and limbs, S-shape or whorls on the abdomen, and whorls on the scalp. The areas demarcated by Blaschko’s lines do not correspond to any known vascular, nervous, or lymphatic structures in the skin. It is believed that there is loss of heterozygosity and cutaneous mosaicism for mutations leading to the linear distribution of skin diseases seen along Blaschko’s lines. The course of blaschkoid LP in children is usually self-limiting with most children responding well to topical or oral steroid therapy as demonstrated in our case. There have been 20 cases reported in the English literature of childhood linear LP occurring along Blaschko’s lines. In view of the expanding number of patients with this rare clinical presentation, we agree with Kabbash et al’s suggestion that linear LP distributed along the lines of Blaschko should be renamed lichen planus, Blaschko subtype. Commercial support: None identified.
Conclusions: Long-term adalimumab treatment of patients with psoriasis provided sustained and clinically meaningful improvement. Overall, patients who achieved PASI-100 typically had superior dermatology-specific patient reported outcomes compared with patients who achieved PASI-75e99. 100% supported by Abbott.
P2748 Efficacy of adalimumab by disease duration in psoriatic arthritis: Subanalysis of ADEPT Ernest Choy, MD, King’s College, London, United Kingdom; Dafna Gladman, MD, University of Toronto Department of Medicine, Toronto, ON, Canada; Eric Sasso, MD, Abbott Laboratories, Abbott Park, IL, United States Objective: To determine the 24- and 48-week (wk) efficacy of adalimumab for arthritis and psoriasis in ADEPT patients (pts) classified according to duration of psoriatic arthritis (PsA) at baseline (BL). Methods: ADEPT was a placebo (pbo)-controlled, phase III study of adalimumab in pts with active PsA who had failed NSAID therapy. Pts were stratified by methotrexate use and degree of psoriasis (\3% and $3% BSA) and randomized to receive adalimumab 40 mg eow or pbo for 24 wks. Upon completion of ADEPT, pts were eligible to receive adalimumab 40 mg eow in the open-label extension (OLE). The present post-hoc analysis determined efficacy in pts categorized according to BL PsA duration: \2, 2 to \5, 5 to \10, and $10 years (yrs). Analyses were conducted on the ITT population, using NRI for ACR and PASI response rates and LOCF for other measures. Safety was evaluated throughout the study. Results: Of 313 pts (151 adalimumab, 162 pbo) enrolled in ADEPT, 285 entered the OLE. BL data were similar between groups. Overall, at wk 24, ACR20/50/70 response rates were 57/39/23 (adalimumab) vs. 15/6/1 (pbo), and PASI-50/75/90 response rates (pts with $ 3% BSA) were 75/59/42 (adalimumab) vs. 12/1/0 (pbo). For the adalimumab arm, BL PsA disease duration was \ 2 yrs for 26, 2-5 yrs for 29, 5e10 yrs for 35, and $10 yrs for 61 pts. By disease duration subgroup, the wk 24 ACR 20/50/70 response rates were 46*/38z/23y (\2 yrs PsA); 66z/52z/28z (2-5 yrs PsA); 54z/34*/23y (5-10 yrs PsA); and 59z/36z/20y ($ 10 yrs PsA) (*p \ 0.05, yp \ 0.01, zp \ 0.001 vs. pbo). For the 69 adalimumab-treated pts with $ 3% BSA, wk 24 PASI-50/75/90 response rates were 69*/46y/38* (\ 2 yrs), 80z/60y/40* (2-5 yrs), 78z/72z/39z (5-10 yrs) and 75z/69z/46z ($ 10 yrs) (*p \ 0.05, yp \ 0.01, z p \ 0.001 vs. pbo). For the disease-duration subgroups of the 151 adalimumabtreated pts, mean BL HAQ and DAS28 scores were 0.8/0.9/1.0/2.0 and 4.7/4.6/4.8/4.9, respectively; mean changes from BL to wk 24 in HAQ were e0.3*/e0.5z/e0.3/e0.4z (*p \ 0.05, zp \ 0.001 vs. pbo) and in DAS28 were 1.5z/e1.7z/e1.5z/e1.8z (zp \ 0.001). Mean TJC and SJC reduced from BL to wk 24 in all subgroups. Clinical responses were maintained to wk 48 in all disease duration subgroups. Adalimumab was generally well-tolerated during the blinded phase of ADEPT and the first 24 wks of the OLE. Conclusion: Adalimumab had clinical efficacy against arthritis and psoriasis for pts from all categories of PsA disease duration in ADEPT. 100% supported by Abbott Laboratories.
AB186
J AM ACAD DERMATOL
P2750 A cost-efficacy analysis of anti-TNF therapies in psoriasis using PASI scores Ramesh Arjunji, PhD, Centocor, Inc., Horsham, PA, United States; Boxiong Tang, MD, Centocor, Inc., Horsham, PA, United States; Omar Dabbous, MD, Centocor, Inc., Horsham, PA, United States; Mirza Rahman, MD, Centocor, Inc., Horsham, PA, United States Objective: To estimate the cost-efficacy of infliximab and etanercept compared to placebo in patients with moderate to severe psoriasis (PsO) using 24-week PASI scores. Methods: We analyzed the cost-efficacy based on their incremental benefit versus placebo using the number needed to treat (NNT) and cost per successfully treated patient using published clinical trials data; inclusion and exclusion criteria were similar in these pivotal trials. This model estimates the cost-efficacy for the average dose of anti-TNF induction 1 maintenance therapy over a one-year period, compared to placebo. For infliximab, dosed at 5 mg/kg, the average number of vials per dose was 4.5, total infusions per patient per year was 8.75, and administration cost per infusion was $225. Etanercept was assumed to be administered at 50 mg/dose twice a week for the first three months and at 25 mg/dose twice a week for the rest of the year. The cost of adverse events was not included in the cost-efficacy estimation. The PASI-50, PASI-75, and PASI-90 response rates at 24 weeks were used as the measures of efficacy. Patients were included for PASI response if their baseline BSA psoriasis [ = 10%. Results: In the infliximab trial (EXPRESS), based on the 24 week data, the NNT was 1.19, 1.28, and 1.75 for PASI-50, PASI-75, and PASI-90 response, respectively. For infliximab, based on the AWP-15%, the annual cost to achieve NNT was $28,747, $30,959, and $42,365 for PASI-50, PASI-75, and PASI-90 response, respectively. In the etanercept trial (global phase III trial)), based on the 24 week data, the NNT was 1.43 and 1.96 for PASI-50 and PASI-75 response, respectively (efficacy data unavilable for 24 week PASI-90 response). The corresponding annual cost to achieve NNT based on the AWP-15%, was $29,801 and $40,903 for PASI-50 and PASI-75 response, respectively. Conclusions: The cost-efficacy measure based on the NNT and annual cost to achieve NNT showed meaningful difference between infliximab and etanercept. However, the cost-effectiveness in clinical practice will depend on the actual dose used, and the actual effectiveness achieved. Moreover, the incremental costeffectiveness of one product compared to another cannot be reliably estimated without a head-to-head trial. Centocor sponsored study.
FEBRUARY 2007
P2749
PASI-100 is associated with better dermatology-specific patient reported outcomes compared with PASI-75e99: Subanalysis of a phase II psoriasis trial of adalimumab Kenneth Gordon, MD, Dermatology, Evanston Northwestern Healthcare, Skokie, IL, United States; Alexa Kimball, MD, MPH, Massachusetts General and Brigham and Women’s Hospitals, Harvard Medical School, Boston, MA, United States; Richard Langley, MD, Dalhousie University, Halifax, NS, Canada; Martin Okun, MD, PhD, Abbott Laboratories, Abbott Park, IL, United States
Lichen planus along the lines of Blaschko Manjeet Mehmi, MBChB, Birmingham Skin Centre, Birmingham, United Kingdom; Periasamy Balasubramaniam, MBBS, MD, Birmingham Skin Centre, Birmingham, United Kingdom; Virginia Hill, MD, Birmingham Children’s Hospital, Birmingham, United Kingdom
Objective: To determine whether the difference between PASI-100 and PASI-75e99 is clinically meaningful, as assessed by patient reported outcomes in adalimumabtreated patients. Methods: Randomized treatment arms included: 1) placebo (n = 52); 2) adalimumab 80 mg subcutaneously (sc) at week 0, then adalimumab 40 mg sc every other week (eow) starting at week 1 (n = 45); and 3) adalimumab 80 mg sc at weeks 0 and 1, then adalimumab 40 mg sc weekly starting at week 2 (n = 50). At week 12, placebo patients were switched to adalimumab 40 mg eow (placebo/adalimumab eow). Skin (PASI) and patient reported outcomes (DLQI) were assessed up to week 60. Results: At week 60, PASI-75e99/100 response ratios were 38%/17% for the placebo/adalimumab eow 1 adalimumab eow group and 38%/26% for the adalimumab weekly group (observed analysis). Pooling patients with similar percentage PASI improvement across treatment arms, patients with PASI \50 (n = 5), 50e74 (n = 18), 75e99 (n = 54), and 100 (n = 29) at week 60 had mean DLQI scores (lower score indicates better health status) of 3.0, 3.3, 1.8, and 0.3, respectively. Mean reductions from baseline in DLQI were 6.0, 8.8, 11.5, and 11.1, respectively (MCID estimated at 5.7). At week 60, 0%/28%/37%/79% of patients with PASI \50/50e74/75e99/100 had a DLQI score of 0, respectively, 20%/17%/35%/10% had a DLQI score of 1, respectively, 40%/17%/7%/10% had a DLQI score of 2, respectively, and 40%/39%/20%/0% had a DLQI score of $3, respectively.
A 14-year-old boy with a 12-year history of atopic dermatitis presented with a 2-month history of a lichenoid eruption on the forearm and shins, also occurring in a blaschkoid pattern on the left side of his abdomen. A skin biopsy revealed histological features of lichen planus (LP). There was no previous history of hepatitis B or C. The LP responded well to twice daily moderate potency topical steroid application over the course of 3 months. Of all LP patients, 0.24-0.62% display the linear LP variant. Linear LP usually occurs in strips or segments of skin larger than can be explained solely by the Koebner phenomenon. Multiple lesions can be seen in a pattern previously described as zosteriform. Only a few cases have been described occurring along Blaschko’s lines. Blaschko’s lines were first described in 1901. Lesions following Blaschko’s lines present with a characteristic V-shape near the posterior midline, linear pattern on the trunk and limbs, S-shape or whorls on the abdomen, and whorls on the scalp. The areas demarcated by Blaschko’s lines do not correspond to any known vascular, nervous, or lymphatic structures in the skin. It is believed that there is loss of heterozygosity and cutaneous mosaicism for mutations leading to the linear distribution of skin diseases seen along Blaschko’s lines. The course of blaschkoid LP in children is usually self-limiting with most children responding well to topical or oral steroid therapy as demonstrated in our case. There have been 20 cases reported in the English literature of childhood linear LP occurring along Blaschko’s lines. In view of the expanding number of patients with this rare clinical presentation, we agree with Kabbash et al’s suggestion that linear LP distributed along the lines of Blaschko should be renamed lichen planus, Blaschko subtype. Commercial support: None identified.
Conclusions: Long-term adalimumab treatment of patients with psoriasis provided sustained and clinically meaningful improvement. Overall, patients who achieved PASI-100 typically had superior dermatology-specific patient reported outcomes compared with patients who achieved PASI-75e99. 100% supported by Abbott.
P2748 Efficacy of adalimumab by disease duration in psoriatic arthritis: Subanalysis of ADEPT Ernest Choy, MD, King’s College, London, United Kingdom; Dafna Gladman, MD, University of Toronto Department of Medicine, Toronto, ON, Canada; Eric Sasso, MD, Abbott Laboratories, Abbott Park, IL, United States Objective: To determine the 24- and 48-week (wk) efficacy of adalimumab for arthritis and psoriasis in ADEPT patients (pts) classified according to duration of psoriatic arthritis (PsA) at baseline (BL). Methods: ADEPT was a placebo (pbo)-controlled, phase III study of adalimumab in pts with active PsA who had failed NSAID therapy. Pts were stratified by methotrexate use and degree of psoriasis (\3% and $3% BSA) and randomized to receive adalimumab 40 mg eow or pbo for 24 wks. Upon completion of ADEPT, pts were eligible to receive adalimumab 40 mg eow in the open-label extension (OLE). The present post-hoc analysis determined efficacy in pts categorized according to BL PsA duration: \2, 2 to \5, 5 to \10, and $10 years (yrs). Analyses were conducted on the ITT population, using NRI for ACR and PASI response rates and LOCF for other measures. Safety was evaluated throughout the study. Results: Of 313 pts (151 adalimumab, 162 pbo) enrolled in ADEPT, 285 entered the OLE. BL data were similar between groups. Overall, at wk 24, ACR20/50/70 response rates were 57/39/23 (adalimumab) vs. 15/6/1 (pbo), and PASI-50/75/90 response rates (pts with $ 3% BSA) were 75/59/42 (adalimumab) vs. 12/1/0 (pbo). For the adalimumab arm, BL PsA disease duration was \ 2 yrs for 26, 2-5 yrs for 29, 5e10 yrs for 35, and $10 yrs for 61 pts. By disease duration subgroup, the wk 24 ACR 20/50/70 response rates were 46*/38z/23y (\2 yrs PsA); 66z/52z/28z (2-5 yrs PsA); 54z/34*/23y (5-10 yrs PsA); and 59z/36z/20y ($ 10 yrs PsA) (*p \ 0.05, yp \ 0.01, zp \ 0.001 vs. pbo). For the 69 adalimumab-treated pts with $ 3% BSA, wk 24 PASI-50/75/90 response rates were 69*/46y/38* (\ 2 yrs), 80z/60y/40* (2-5 yrs), 78z/72z/39z (5-10 yrs) and 75z/69z/46z ($ 10 yrs) (*p \ 0.05, yp \ 0.01, z p \ 0.001 vs. pbo). For the disease-duration subgroups of the 151 adalimumabtreated pts, mean BL HAQ and DAS28 scores were 0.8/0.9/1.0/2.0 and 4.7/4.6/4.8/4.9, respectively; mean changes from BL to wk 24 in HAQ were e0.3*/e0.5z/e0.3/e0.4z (*p \ 0.05, zp \ 0.001 vs. pbo) and in DAS28 were 1.5z/e1.7z/e1.5z/e1.8z (zp \ 0.001). Mean TJC and SJC reduced from BL to wk 24 in all subgroups. Clinical responses were maintained to wk 48 in all disease duration subgroups. Adalimumab was generally well-tolerated during the blinded phase of ADEPT and the first 24 wks of the OLE. Conclusion: Adalimumab had clinical efficacy against arthritis and psoriasis for pts from all categories of PsA disease duration in ADEPT. 100% supported by Abbott Laboratories.
AB186
J AM ACAD DERMATOL
P2750 A cost-efficacy analysis of anti-TNF therapies in psoriasis using PASI scores Ramesh Arjunji, PhD, Centocor, Inc., Horsham, PA, United States; Boxiong Tang, MD, Centocor, Inc., Horsham, PA, United States; Omar Dabbous, MD, Centocor, Inc., Horsham, PA, United States; Mirza Rahman, MD, Centocor, Inc., Horsham, PA, United States Objective: To estimate the cost-efficacy of infliximab and etanercept compared to placebo in patients with moderate to severe psoriasis (PsO) using 24-week PASI scores. Methods: We analyzed the cost-efficacy based on their incremental benefit versus placebo using the number needed to treat (NNT) and cost per successfully treated patient using published clinical trials data; inclusion and exclusion criteria were similar in these pivotal trials. This model estimates the cost-efficacy for the average dose of anti-TNF induction 1 maintenance therapy over a one-year period, compared to placebo. For infliximab, dosed at 5 mg/kg, the average number of vials per dose was 4.5, total infusions per patient per year was 8.75, and administration cost per infusion was $225. Etanercept was assumed to be administered at 50 mg/dose twice a week for the first three months and at 25 mg/dose twice a week for the rest of the year. The cost of adverse events was not included in the cost-efficacy estimation. The PASI-50, PASI-75, and PASI-90 response rates at 24 weeks were used as the measures of efficacy. Patients were included for PASI response if their baseline BSA psoriasis [ = 10%. Results: In the infliximab trial (EXPRESS), based on the 24 week data, the NNT was 1.19, 1.28, and 1.75 for PASI-50, PASI-75, and PASI-90 response, respectively. For infliximab, based on the AWP-15%, the annual cost to achieve NNT was $28,747, $30,959, and $42,365 for PASI-50, PASI-75, and PASI-90 response, respectively. In the etanercept trial (global phase III trial)), based on the 24 week data, the NNT was 1.43 and 1.96 for PASI-50 and PASI-75 response, respectively (efficacy data unavilable for 24 week PASI-90 response). The corresponding annual cost to achieve NNT based on the AWP-15%, was $29,801 and $40,903 for PASI-50 and PASI-75 response, respectively. Conclusions: The cost-efficacy measure based on the NNT and annual cost to achieve NNT showed meaningful difference between infliximab and etanercept. However, the cost-effectiveness in clinical practice will depend on the actual dose used, and the actual effectiveness achieved. Moreover, the incremental costeffectiveness of one product compared to another cannot be reliably estimated without a head-to-head trial. Centocor sponsored study.
FEBRUARY 2007