- Email: [email protected]
Fatigue outcomes following withdrawal from and retreatment with adalimumab among patients maintained on adalimumab for moderate to severe psoriasis
P3347
P3349
Successful treatment of moderate to severe plaque psoriasis of the scalp with clobetasol propionate spray, 0.05% Fran E. Cook Bolden, MD, Research Division of the Skin Specialty Group, New York, NY, United States; Bernard S. Goffe, MD, Dermatology Associates, Seattle, WA, United States; Howard L. Sofen, MD, Dermatology Research Associates, Los Angeles, CA, United States; Luz E. Colon, MS, Galderma Laboratories, Fort Worth, TX, United States; Ronald W. Gottschalk, MD, Galderma Laboratories, Fort Worth, TX, United States This study provided additional safety and efficacy data of clobetasol propionate (CP) spray, 0.05% compared to vehicle spray in the treatment of moderate to severe plaque psoriasis of the scalp. This was a multicenter, randomized, double-blind, vehicle-controlled trial of 81 patients, 18 years or older, with moderate to severe plaque psoriasis of the scalp. Patients applied CP spray, 0.05% or vehicle spray to affected area twice daily for 4 weeks. Patients were evaluated for efficacy and safety at baseline and weeks 2 and 4. Patients who were clear at week 2 completed the study at that time. A patient survey addressing the practicability of using a new pump applicator for CP spray, 0.05% delivery was administered at the end of the study. Most of the patients in the ITT population were female (60%, n ¼ 49) and white (78%, n ¼ 63) with Fitzpatrick skin type III (38%, n ¼ 31) or IV (28%, n ¼ 23). The mean history of psoriasis was 11.1 years and mean body surface area affected (including scalp) was 5.2%. At end of treatment, the majority of patients were clear (51%, n ¼ 21) or almost clear (34%, n ¼ 14) in the CP spray, 0.05% group and mild (28%, n ¼ 11) or moderate (45%, n ¼ 18) in the vehicle spray group. The distribution of global severity scores at the end of treatment showed treatment success in 85% of CP spray, 0.05% treated patients versus 13% of vehicle treated patients (P \.001). The majority of the patients in the CP spray, 0.05% group had moderate pruritus (71%, n ¼ 29) at baseline and no pruritus (68%, n ¼ 28) at end of treatment while the majority in the vehicle group had moderate pruritus (60%, n ¼ 24) at baseline and mild (35%, n ¼ 14) or moderate (35%, n ¼ 14) pruritus at end of treatment. Most of the patients had no stinging/burning (68%, n ¼ 38) with CP spray, 0.05% while the vehicle arm had none (40%, n ¼ 16) or mild (38%, n ¼ 15). Patient satisfaction survey results indicated the majority of patients in both groups strongly agreed/agreed the pump applicator made the study products easy to apply to the scalp (CP spray: 85%, n ¼ 35; vehicle: 85%, n ¼ 34) and the directional nozzle on the pump made it easy to apply the products to psoriasis plaques on their scalps (CP spray: 80%, n ¼ 33; vehicle: 88%, n ¼ 35). There were a total of 16 adverse events (AEs) reported by 8 patients in the CP spray, 0.05% group and six AEs reported by five patients in the vehicle spray group. Most of the AEs were mild or moderate in severity and definitely unrelated or unlikely to be related to the study medication.
Analysis of vitamin D analogs for treatment of psoriasis Farah Awadalla, MD, Virginia Commonwealth University, Richmond, VA, United States; Brad Yentzer, MD, WFU School of Medicine, Winston Salem, NC, United States; Steven Feldman, MD, PhD, WFU School of Medicine, Winston Salem, NC, United States Background: Psoriasis is one of the most common dermatologic diseases, and vitamin D analogs are a nonsteroid alternative for topical treatment. Our objective is to assess the use of topical steroids and vitamin D analogues in the treatment of psoriasis. Methods: Study researchers analyzed the National Ambulatory Medical Care Survey data from 1994 to 2007 for the diagnosis of psoriasis and prescriptions for topical corticosteroid use as well as calcipotriene. Results: There were an estimated 27 million psoriasis encounters from 1994 to 2007. Dermatologists were responsible for 68% of these encounters followed by family practice and internal medicine with 11.19% and 10.95% of encounters, respectively. Dermatologists prescribed calcipotriene in 17.55%, followed by rheumatology with 10.91%, family practice with 8.91%, and internal medicine with 6.07%. The use of calcipotriene in psoriasis encounters from 1994 to 2007 ranged from 7.17% to 21.7%. It was prescribed slightly more for men than women, and most frequently prescribed for whites than other races. Calcipotriene plus betamethasone was prescribed in 13.01% and 8.33% of psoriasis visits in 2006 and 2007, respectively. Unlike calcipotriene alone, calcipotriene plus betamethasone was prescribed 3 times as much for women with psoriasis than men. Dermatologists were responsible for 85%, 73.98%, and 81.72% of all prescriptions throughout specialties to treat psoriasis with calcipotriene, calcipotriene plus betamethasone, and other topical corticosteroids, respectively. Discussion: Psoriasis is mostly treated by dermatologists who on average use topical steroids in 50% of visits and vitamin D analogues in approximately 10% to 20% of visits. It is unclear why there is a discrepancy in prescribing of vitamin D analogs for different sexes and races. Nonetheless, physicians may be underusing them for psoriasis treatment. Commercial support: None identified.
Commercial support: Support provided by Galderma Laboratories.
P3350
P3348 Safety and bioavailability of two calcipotriene formulations in subjects with mild to moderate plaque-type psoriasis Robert Matheson, MD, Oregon Medical Research Center, Portland, OR, United States; Edward Hsia, Stiefel, a GSK company, Palo Alto, CA, United States; Melody Wyres, Stiefel, a GSK company, Palo Alto, CA, United States; Xue Ge, Stiefel, a GSK company, Palo Alto, CA, United States Calcipotriene is a vitamin D3 analogue used as therapy for psoriasis. Calcipotriene foam 0.005% uses a novel foam vehicle technology that was developed to make it easy to apply and to spread over large body surface areas while delivering calcipotriene without residue, a deficiency of other vehicles. The objective of this study was to evaluate the safety and bioavailability of calcipotriene foam, 0.005% and calcipotriene ointment, 0.005% in subjects with plaque-type psoriasis. This singlecenter, open-label study randomized subjects with plaque-type psoriasis in a 1:1 ratio to calcipotriene foam or ointment. Subjects applied a fixed-dose of 3.5 g of study product twice-daily for 2 weeks to all affected psoriatic areas of the body. Safety was assessed based upon adverse event (AE) reporting and changes in albumin-adjusted serum calcium levels to evaluate the effect on calcium metabolism. A bioanalytical assay was developed and validated to measure the circulating plasma levels of calcipotriene using reversed-phase high-performance liquid chromatography and mass spectrometry with a lower limit of quantification of 10 pg/mL, the most sensitive method ever reported. Bioavailability was evaluated within 1 hour before treatment application on days 1, 8 (and at 1, 3, 6, and 10 hours after morning application), and 15 (and at 1 hour after morning application). Thirty-two subjects (16:16 foam and ointment) were enrolled with similar mean percent body surface areas affected between the treatment groups. The median daily product usage was higher (6.80 g) in subjects using calcipotriene foam than in subjects using calcipotriene ointment (5.55 g). No albumin-adjusted calcium levels were above the upper limit of normal. No serious or unusual AEs reported were reported. Because only six subjects (1 in calcipotriene foam group; 5 in calcipotriene ointment group) had measurable levels of calcipotriene (all below 25pg/mL) during the study, pharmacokinetic parameters including Cmax, Tmax, and AUC could not be computed. The measurable concentrations indicated there was no significant difference in the systemic exposure and accumulation of calcipotriene between topically administered foam and ointment formulations. Topical application of calcipotriene foam or calcipotriene ointment twice daily for 2 consecutive weeks appeared to be safe, well tolerated, and resulted in similarly low systemic exposure in subjects $ 12 years of age with mild to moderate plaque-type psoriasis. Commercial support: 100% sponsored by Stiefel, a GSK company.
FEBRUARY 2011
Fatigue outcomes following withdrawal from and retreatment with adalimumab among patients maintained on adalimumab for moderate to severe psoriasis Kim Papp, Probity Medical Research, Waterloo, Ontario, Canada; Eric Wu, Analysis Group, Boston, MA, United States; Orin Goldblum, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott Laboratories, Abbott Park, IL, United States Objective: To describe fatigue outcomes following withdrawal from and retreatment with adalimumab (ADA) treatment for moderate to severe psoriasis (Ps). Methods: Patients maintained on open-label ADA with a Physician’s Global Assessment (PGA) of ‘‘clear’’ or ‘‘minimal’’ at two consecutive visits were subsequently withdrawn from ADA and followed until relapse (PGA ‘‘moderate’’ or worse) or end of study phase. Sixteen weeks of ADA retreatment were then initiated with an 80-mg dose followed by 40 mg every other week. The Functional Assessment of Chronic Illness TherapyeFatigue (FACIT-F) questionnaire was assessed at withdrawal and every 4 weeks thereafter. FACIT-F scores range from 0 (worst) to 52 (best) and were described as mean scores compared to the general population (GP; mean ¼ 43.6) after withdrawal and retreatment, and proportions of patients with changes $ the minimum clinically important difference (MCID; 3 units). Pearson correlations were assessed between changes in FACIT-F, Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). Analyses were stratified by relapse status and history of psoriatic arthritis (PsA). Results: Before withdrawal (N ¼ 280), mean FACIT-F was 44.8, comparable to GP. After withdrawal (N ¼ 265), mean FACIT-F was 41.9, significantly worse than GP (P ¼ .01), and 58% had experienced $ MCID worsening in FACIT-F. Proportions with $ MCID worsening were greater among patients with (N ¼ 165) versus without (N ¼ 100) relapse (62 vs 50%; P ¼ .049) and those with (N ¼ 63) versus without (N ¼ 202) PsA (71% vs 53%; P ¼ .01). After 16 weeks of ADA retreatment, mean FACIT-F was 44.4 (comparable to GP); 49% experienced $ MCID improvement. During retreatment, proportions with $ MCID improvement were greater among patients with vs. without prior relapse (54% vs 40%; P ¼ .02) and those with versus without PsA (60% vs 45%; P ¼ .03). Improvements in FACIT-F were positively correlated with improvements in PASI (r ¼ 0.20; P \ .01) and DLQI (r ¼ 0.46; P \.01) after retreatment. Conclusions: Ps patients maintained on ADA had mean fatigue similar to the GP. Withdrawal of ADA was associated with clinically significant worsening of fatigue for the majority of patients, and especially for patients allowed to relapse before restarting ADA or with a history of PsA. After restarting ADA, fatigue returned to levels seen in the GP. The reductions in fatigue showed greater correlation with improvements in dermatologic quality of life than with signs of skin disease. Commercial support: This study was funded by Abbott Laboratories.
J AM ACAD DERMATOL
AB157
P3349
Successful treatment of moderate to severe plaque psoriasis of the scalp with clobetasol propionate spray, 0.05% Fran E. Cook Bolden, MD, Research Division of the Skin Specialty Group, New York, NY, United States; Bernard S. Goffe, MD, Dermatology Associates, Seattle, WA, United States; Howard L. Sofen, MD, Dermatology Research Associates, Los Angeles, CA, United States; Luz E. Colon, MS, Galderma Laboratories, Fort Worth, TX, United States; Ronald W. Gottschalk, MD, Galderma Laboratories, Fort Worth, TX, United States This study provided additional safety and efficacy data of clobetasol propionate (CP) spray, 0.05% compared to vehicle spray in the treatment of moderate to severe plaque psoriasis of the scalp. This was a multicenter, randomized, double-blind, vehicle-controlled trial of 81 patients, 18 years or older, with moderate to severe plaque psoriasis of the scalp. Patients applied CP spray, 0.05% or vehicle spray to affected area twice daily for 4 weeks. Patients were evaluated for efficacy and safety at baseline and weeks 2 and 4. Patients who were clear at week 2 completed the study at that time. A patient survey addressing the practicability of using a new pump applicator for CP spray, 0.05% delivery was administered at the end of the study. Most of the patients in the ITT population were female (60%, n ¼ 49) and white (78%, n ¼ 63) with Fitzpatrick skin type III (38%, n ¼ 31) or IV (28%, n ¼ 23). The mean history of psoriasis was 11.1 years and mean body surface area affected (including scalp) was 5.2%. At end of treatment, the majority of patients were clear (51%, n ¼ 21) or almost clear (34%, n ¼ 14) in the CP spray, 0.05% group and mild (28%, n ¼ 11) or moderate (45%, n ¼ 18) in the vehicle spray group. The distribution of global severity scores at the end of treatment showed treatment success in 85% of CP spray, 0.05% treated patients versus 13% of vehicle treated patients (P \.001). The majority of the patients in the CP spray, 0.05% group had moderate pruritus (71%, n ¼ 29) at baseline and no pruritus (68%, n ¼ 28) at end of treatment while the majority in the vehicle group had moderate pruritus (60%, n ¼ 24) at baseline and mild (35%, n ¼ 14) or moderate (35%, n ¼ 14) pruritus at end of treatment. Most of the patients had no stinging/burning (68%, n ¼ 38) with CP spray, 0.05% while the vehicle arm had none (40%, n ¼ 16) or mild (38%, n ¼ 15). Patient satisfaction survey results indicated the majority of patients in both groups strongly agreed/agreed the pump applicator made the study products easy to apply to the scalp (CP spray: 85%, n ¼ 35; vehicle: 85%, n ¼ 34) and the directional nozzle on the pump made it easy to apply the products to psoriasis plaques on their scalps (CP spray: 80%, n ¼ 33; vehicle: 88%, n ¼ 35). There were a total of 16 adverse events (AEs) reported by 8 patients in the CP spray, 0.05% group and six AEs reported by five patients in the vehicle spray group. Most of the AEs were mild or moderate in severity and definitely unrelated or unlikely to be related to the study medication.
Analysis of vitamin D analogs for treatment of psoriasis Farah Awadalla, MD, Virginia Commonwealth University, Richmond, VA, United States; Brad Yentzer, MD, WFU School of Medicine, Winston Salem, NC, United States; Steven Feldman, MD, PhD, WFU School of Medicine, Winston Salem, NC, United States Background: Psoriasis is one of the most common dermatologic diseases, and vitamin D analogs are a nonsteroid alternative for topical treatment. Our objective is to assess the use of topical steroids and vitamin D analogues in the treatment of psoriasis. Methods: Study researchers analyzed the National Ambulatory Medical Care Survey data from 1994 to 2007 for the diagnosis of psoriasis and prescriptions for topical corticosteroid use as well as calcipotriene. Results: There were an estimated 27 million psoriasis encounters from 1994 to 2007. Dermatologists were responsible for 68% of these encounters followed by family practice and internal medicine with 11.19% and 10.95% of encounters, respectively. Dermatologists prescribed calcipotriene in 17.55%, followed by rheumatology with 10.91%, family practice with 8.91%, and internal medicine with 6.07%. The use of calcipotriene in psoriasis encounters from 1994 to 2007 ranged from 7.17% to 21.7%. It was prescribed slightly more for men than women, and most frequently prescribed for whites than other races. Calcipotriene plus betamethasone was prescribed in 13.01% and 8.33% of psoriasis visits in 2006 and 2007, respectively. Unlike calcipotriene alone, calcipotriene plus betamethasone was prescribed 3 times as much for women with psoriasis than men. Dermatologists were responsible for 85%, 73.98%, and 81.72% of all prescriptions throughout specialties to treat psoriasis with calcipotriene, calcipotriene plus betamethasone, and other topical corticosteroids, respectively. Discussion: Psoriasis is mostly treated by dermatologists who on average use topical steroids in 50% of visits and vitamin D analogues in approximately 10% to 20% of visits. It is unclear why there is a discrepancy in prescribing of vitamin D analogs for different sexes and races. Nonetheless, physicians may be underusing them for psoriasis treatment. Commercial support: None identified.
Commercial support: Support provided by Galderma Laboratories.
P3350
P3348 Safety and bioavailability of two calcipotriene formulations in subjects with mild to moderate plaque-type psoriasis Robert Matheson, MD, Oregon Medical Research Center, Portland, OR, United States; Edward Hsia, Stiefel, a GSK company, Palo Alto, CA, United States; Melody Wyres, Stiefel, a GSK company, Palo Alto, CA, United States; Xue Ge, Stiefel, a GSK company, Palo Alto, CA, United States Calcipotriene is a vitamin D3 analogue used as therapy for psoriasis. Calcipotriene foam 0.005% uses a novel foam vehicle technology that was developed to make it easy to apply and to spread over large body surface areas while delivering calcipotriene without residue, a deficiency of other vehicles. The objective of this study was to evaluate the safety and bioavailability of calcipotriene foam, 0.005% and calcipotriene ointment, 0.005% in subjects with plaque-type psoriasis. This singlecenter, open-label study randomized subjects with plaque-type psoriasis in a 1:1 ratio to calcipotriene foam or ointment. Subjects applied a fixed-dose of 3.5 g of study product twice-daily for 2 weeks to all affected psoriatic areas of the body. Safety was assessed based upon adverse event (AE) reporting and changes in albumin-adjusted serum calcium levels to evaluate the effect on calcium metabolism. A bioanalytical assay was developed and validated to measure the circulating plasma levels of calcipotriene using reversed-phase high-performance liquid chromatography and mass spectrometry with a lower limit of quantification of 10 pg/mL, the most sensitive method ever reported. Bioavailability was evaluated within 1 hour before treatment application on days 1, 8 (and at 1, 3, 6, and 10 hours after morning application), and 15 (and at 1 hour after morning application). Thirty-two subjects (16:16 foam and ointment) were enrolled with similar mean percent body surface areas affected between the treatment groups. The median daily product usage was higher (6.80 g) in subjects using calcipotriene foam than in subjects using calcipotriene ointment (5.55 g). No albumin-adjusted calcium levels were above the upper limit of normal. No serious or unusual AEs reported were reported. Because only six subjects (1 in calcipotriene foam group; 5 in calcipotriene ointment group) had measurable levels of calcipotriene (all below 25pg/mL) during the study, pharmacokinetic parameters including Cmax, Tmax, and AUC could not be computed. The measurable concentrations indicated there was no significant difference in the systemic exposure and accumulation of calcipotriene between topically administered foam and ointment formulations. Topical application of calcipotriene foam or calcipotriene ointment twice daily for 2 consecutive weeks appeared to be safe, well tolerated, and resulted in similarly low systemic exposure in subjects $ 12 years of age with mild to moderate plaque-type psoriasis. Commercial support: 100% sponsored by Stiefel, a GSK company.
FEBRUARY 2011
Fatigue outcomes following withdrawal from and retreatment with adalimumab among patients maintained on adalimumab for moderate to severe psoriasis Kim Papp, Probity Medical Research, Waterloo, Ontario, Canada; Eric Wu, Analysis Group, Boston, MA, United States; Orin Goldblum, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott Laboratories, Abbott Park, IL, United States Objective: To describe fatigue outcomes following withdrawal from and retreatment with adalimumab (ADA) treatment for moderate to severe psoriasis (Ps). Methods: Patients maintained on open-label ADA with a Physician’s Global Assessment (PGA) of ‘‘clear’’ or ‘‘minimal’’ at two consecutive visits were subsequently withdrawn from ADA and followed until relapse (PGA ‘‘moderate’’ or worse) or end of study phase. Sixteen weeks of ADA retreatment were then initiated with an 80-mg dose followed by 40 mg every other week. The Functional Assessment of Chronic Illness TherapyeFatigue (FACIT-F) questionnaire was assessed at withdrawal and every 4 weeks thereafter. FACIT-F scores range from 0 (worst) to 52 (best) and were described as mean scores compared to the general population (GP; mean ¼ 43.6) after withdrawal and retreatment, and proportions of patients with changes $ the minimum clinically important difference (MCID; 3 units). Pearson correlations were assessed between changes in FACIT-F, Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). Analyses were stratified by relapse status and history of psoriatic arthritis (PsA). Results: Before withdrawal (N ¼ 280), mean FACIT-F was 44.8, comparable to GP. After withdrawal (N ¼ 265), mean FACIT-F was 41.9, significantly worse than GP (P ¼ .01), and 58% had experienced $ MCID worsening in FACIT-F. Proportions with $ MCID worsening were greater among patients with (N ¼ 165) versus without (N ¼ 100) relapse (62 vs 50%; P ¼ .049) and those with (N ¼ 63) versus without (N ¼ 202) PsA (71% vs 53%; P ¼ .01). After 16 weeks of ADA retreatment, mean FACIT-F was 44.4 (comparable to GP); 49% experienced $ MCID improvement. During retreatment, proportions with $ MCID improvement were greater among patients with vs. without prior relapse (54% vs 40%; P ¼ .02) and those with versus without PsA (60% vs 45%; P ¼ .03). Improvements in FACIT-F were positively correlated with improvements in PASI (r ¼ 0.20; P \ .01) and DLQI (r ¼ 0.46; P \.01) after retreatment. Conclusions: Ps patients maintained on ADA had mean fatigue similar to the GP. Withdrawal of ADA was associated with clinically significant worsening of fatigue for the majority of patients, and especially for patients allowed to relapse before restarting ADA or with a history of PsA. After restarting ADA, fatigue returned to levels seen in the GP. The reductions in fatigue showed greater correlation with improvements in dermatologic quality of life than with signs of skin disease. Commercial support: This study was funded by Abbott Laboratories.
J AM ACAD DERMATOL
AB157