Ruxolitinib-associated exfoliative dermatitis
1
P6346 Onychopharmacokinetics of terbinafine hydrochloride penetration from a novel topical formulation into the human nail in vitro Xiaoying Hui, MD, University of California San Francisco, Dermatology, San Francisco, CA, United States; Ake Lindahl, Zelmic AB, Lund, Sweden; Maibach Howard, MD, University of California San Francisco, Dermatology, San Francisco, CA, United States; Sonia Lamel, MD, University of California San Francisco, Dermatology, San Francisco, CA, United States This study determined the onychopharmacokinetics, nail absorption, distribution, and penetration of [14C]-terbinafine hydrochloride in a new topical formulation into/through the human finger nail using the in vitro finite dose model. This study determined the penetration rate of terbinafine hydrochloride from multiple doses of topical formulation applied daily for 14 days. Results showed that the total dose recovery (mass balance) was almost 100%. The concentration of terbinafine hydrochloride in the deeper nail plate (ventral/intermediate layers) and the cotton pad nail bed samples after the 14-day treatment were 613 6 145g/g and (6 S.D.) and 27 6 1.2 g/cm 3 (or 1.9 6 0.6 g/cm 3 daily) on average, respectively. In comparison with nail concentration data from literature, the results show that higher amounts of terbinafine hydrochloride reached the deep nail plate and/or the nail bed after a 14-day topical treatment with this topical formulation in vitro. Commercial support: None identified. P6579 Patients adherence and biologic drug survival in dermatology: An Italian center experience Andrea D’Alessio, Hospital Pharmacy, University Hospital A. Gemelli, Rome, Italy; Barbara Bolletta, Hospital Pharmacy, University Hospital A. Gemelli, Rome, Italy; Clara De Simone, Dermatology Unit, University Hospital A. Gemelli, Rome, Italy; Enrica Maria Proli, Hospital Pharmacy, University Hospital A. Gemelli, Rome, Italy; Leonardo Celleno, Dermatology Unit, Columbus Integrated Complex, Rome, Italy; Nicoletta Virginia Pecora, Hospital Pharmacy, Columbus Integrated Complex, Rome, Italy; Rita Fraschetti, Hospital Pharmacy, University Hospital A. Gemelli, Rome, Italy Background: Biologic drugs are a therapeutic option in treating psoriasis (Pso). Their efficacy and safety profile have been widely documented. However some issues, like patient compliance, need more attention, because they are possible causes of poor therapy adherence. The objective is to compare drug survival in Pso patients (pts) and to identify possible predictors of treatment adherence. Methods: Pts with Pso under treatment with biologic drugs (TNF alfa blockers etanercept and adalimumab and anti-IL12/23 ustekinumab) during 2011 were included in a prospective observational study conducted by Gemelli Hospital and Columbus Integrated Complex pharmacies. Pts data collected included: age, sex, disease and drug. The sample was characterized by compliance and therapy duration using mean and standard deviation (for continuous variables), frequency and percentage (categorical variables). Time to drug discontinuation was evaluated as the difference between starting date of treatment and date of drug termination or end of study. Differences in drug discontinuation time were analysed using Kaplan- Meier curves and assessed by the log-rank test. The identification of the reasons for therapy discontinuation was performed using a multivariate Cox regression model. Results were expressed as hazard ratios (HRs) and confidence intervals at 95% (95% CI). Results: 180 pts with a mean age of 49 years (613.2) and mean treatment duration of 18.6 months (615.3) were analyzed. Overall global retention rate was 75% (Eta 72.9%, Ada 74.2%, Ust 86.4%). All kind of interruptions occurred in 45 pts (25%), these were caused by clinical remission in 11 pts (6.1%; Eta 3.1%, Ada 11.3%, Ust 4.6% respectively), adverse reactions in 9 pts (5%; Eta 7, 3%, Ada 3.2%), inefficacy in 13 pts (7.2%; Eta 6.3%, Ada 8.1%, Ust 9.1%). 24-months survival rate was lower with Eta, but not significantly because of poor sample size (HR 1.12- 95%CI 0.22-5.7; P ¼ .9). Conclusions: The results obtained demonstrate biologics effectiveness in the treatment of Pso in terms of clinical remission that allowed therapy discontinuation. A good long term global retention has been documented. Adherence was instead influenced by adverse reactions and inefficacy appearance. Data highlight some factors that may determine therapeutic failure of biological drugs in Pso pts, but these findings need further confirmation in larger population, with a longer follow-up. Commercial support: None identified. P7076 Ruxolitinib-associated exfoliative dermatitis John Fournier, MD, Roger Williams Medical Center, Deparment of Dermatology and Skin Surgery, Providence, RI, United States; Catherine Breen, MD, Roger Williams Medical Center, Department of Dermatology and Skin Surgery, Providence, RI, United States; Linda Zhou, MD, Roger Williams Medical Center, Department of Dermatology and Skin Surgery, Providence, RI, United States; Satori Iwamoto, MD, PhD, Roger Williams Medical Center, Department of Dermatology and Skin Surgery, Providence, RI, United States A 61-year-old male with a 15-year history of myelofibrosis presented to the emergency room with a 1-week history of leg swelling, shortness of breath, and rash. The patient was subsequently admitted to the hospital with lower leg edema, anemia, and rash. Physical examination revealed erythematous macules and 2- to 3-mm erythematous papules on the trunk and upper and lower extremities. Over the next several days the morbilliform rash evolved into widespread confluent erythema over the trunk and extremities. A 3-mm punch biopsy was done on the left arm. Superficial and deep perivascular granulomatous inflammation composed of lymphocytes, histiocytes, rare foreign body giant cells, and scattered eosinophils was seen on biopsy. Clinicopathologic correlation supported a drug reaction. Ruxolitinib was tapered over the next several weeks. The patient was also treated with the aggressive use of emollients, as well as triamcinolone 0.1% cream to the trunk, desonide 0.05% cream to the face, and an oral prednisone taper. Significant improvement, namely reduced erythema and diminished scale, was seen within 1 week of the onset of treatment. There was near resolution of the exfoliative dermatitis several weeks after discharge from the hospital. Three weeks before the appearance of the morbilliform rash the patient began ruxolitinib for the treatment of myelofibrosis. He had no other new medications within the previous 6 months. Ruxolitinib is a novel treatment approved for myelofibrosis in 2011. Ruxolitinib is an orally bioavailable selective inhibitor of JAK1 and JAK2. A result of this selective inhibition is decreased levels of phosphorylated JAK2, and therefore decreased activity of the JAK/STAT pathway. To the best of our knowledge this is the first reported case of ruxolitinib associated with rash or exfoliative dermatitis. Commercial support: None identified. P6966 The effect of folate supplementation on methotrexate efficacy in psoriasis patients Amir Al-Dabagh, Wake Forest School of Medicine, Winston-Salem, NC, United States; Megan Kinney, MD, Wake Forest School of Medicine, Winston-Salem, NC, United States; Scott Davis, Wake Forest School of Medicine, Winston-Salem, NC, United States; Steve Feldman, MD, PhD, Wake Forest School of Medicine, Winston-Salem, NC, United States Background: Methotrexate (MTX) is an effective treatment for psoriasis but its use is limited by its toxicity. Folate has been supplemented to reduce adverse events, although it may influence efficacy. Purpose: The objective of this study was to review the literature involving the use of folate in patients (particular those with psoriasis) treated with MTX and analyze current trends in folate use. Methods: We searched PubMed from 1 May 1989 through 1 April 2012 using the terms ‘‘folic acid,’’ ‘‘folinic acid,’’ ‘‘supplementation,’’ and ‘‘methotrexate.’’ We also used the National Ambulatory Medical Care Survey database (NAMCS) to collect data regarding trends in MTX use and folate supplementation by physicians in the United States from 1993 through 2009. We assessed data including number of MTX visits, rate of folate use, diagnoses, specialty of physician, and demographics of patients. We used linear regression to analyze the change in folic acid use over time. Results: Twenty-nine published trials were included addressing folic acid supple- mentation with MTX; the majority found a benefit to folic acid supplementation, but there were only 9 in psoriasis. Dermatologists were among the highest prescribers of MTX, and psoriasis was also commonly treated with MTX. Folic acid supplemen- tation significantly increased over this time period (P \ .0001). However, dermatologists ranked lowest for their folate use, coprescribing folate to only 9.1% of MTX-treated patients. Limitations: Data only included outpatient visits to nonefederally employed physicians. Also, in contrast to rheumatoid arthritis, there is a scarcity of literature describing the effect of folate on MTX toxicity and efficacy in psoriasis patients. Conclusion: Dermatologists were the least likely specialists to supplement MTX with folic acid. Additional studies with larger sample sizes are warranted to form an accurate and complete assessment of folate’s influence on MTX toxicity and efficacy in psoriasis patients. Commercial support: None identified. APRIL 2013 JAM ACAD DERMATOL AB181
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Transcript of Ruxolitinib-associated exfoliative dermatitis
P6346Onychopharmacokinetics of terbinafine hydrochloride penetration froma novel topical formulation into the human nail in vitro
Xiaoying Hui, MD, University of California San Francisco, Dermatology, SanFrancisco, CA, United States; �Ake Lindahl, Zelmic AB, Lund, Sweden; MaibachHoward, MD, University of California San Francisco, Dermatology, San Francisco,CA, United States; Sonia Lamel, MD, University of California San Francisco,Dermatology, San Francisco, CA, United States
This study determined the onychopharmacokinetics, nail absorption, distribution,and penetration of [14C]-terbinafine hydrochloride in a new topical formulationinto/through the human finger nail using the in vitro finite dose model. This studydetermined the penetration rate of terbinafine hydrochloride frommultiple doses oftopical formulation applied daily for 14 days. Results showed that the total doserecovery (mass balance) was almost 100%. The concentration of terbinafinehydrochloride in the deeper nail plate (ventral/intermediate layers) and the cottonpad nail bed samples after the 14-day treatment were 613 6 145�g/g and (6 S.D.)and 27 6 1.2 �g/cm3 (or 1.9 6 0.6 �g/cm3 daily) on average, respectively. Incomparison with nail concentration data from literature, the results show thathigher amounts of terbinafine hydrochloride reached the deep nail plate and/or thenail bed after a 14-day topical treatment with this topical formulation in vitro.
APRIL 20
cial support: None identified.
CommerP6579Patients adherence and biologic drug survival in dermatology: An Italiancenter experience
Andrea D’Alessio, Hospital Pharmacy, University Hospital A. Gemelli, Rome,Italy; Barbara Bolletta, Hospital Pharmacy, University Hospital A. Gemelli, Rome,Italy; Clara De Simone, Dermatology Unit, University Hospital A. Gemelli, Rome,Italy; Enrica Maria Proli, Hospital Pharmacy, University Hospital A. Gemelli,Rome, Italy; Leonardo Celleno, Dermatology Unit, Columbus IntegratedComplex, Rome, Italy; Nicoletta Virginia Pecora, Hospital Pharmacy, ColumbusIntegrated Complex, Rome, Italy; Rita Fraschetti, Hospital Pharmacy, UniversityHospital A. Gemelli, Rome, Italy
Background: Biologic drugs are a therapeutic option in treating psoriasis (Pso). Theirefficacy and safety profile have been widely documented. However some issues, likepatient compliance, need more attention, because they are possible causes of poortherapy adherence. The objective is to compare drug survival in Pso patients (pts)and to identify possible predictors of treatment adherence.
Methods: Pts with Pso under treatment with biologic drugs (TNF alfa blockersetanercept and adalimumab and anti-IL12/23 ustekinumab) during 2011 wereincluded in a prospective observational study conducted by Gemelli Hospital andColumbus Integrated Complex pharmacies. Pts data collected included: age, sex,disease and drug. The sample was characterized by compliance and therapyduration using mean and standard deviation (for continuous variables), frequencyand percentage (categorical variables). Time to drug discontinuation was evaluatedas the difference between starting date of treatment and date of drug termination orend of study. Differences in drug discontinuation time were analysed using Kaplan-Meier curves and assessed by the log-rank test. The identification of the reasons fortherapy discontinuation was performed using a multivariate Cox regression model.Results were expressed as hazard ratios (HRs) and confidence intervals at 95% (95%CI).
Results: 180 pts with a mean age of 49 years (613.2) andmean treatment duration of18.6 months (615.3) were analyzed. Overall global retention rate was 75% (Eta72.9%, Ada 74.2%, Ust 86.4%). All kind of interruptions occurred in 45 pts (25%),these were caused by clinical remission in 11 pts (6.1%; Eta 3.1%, Ada 11.3%, Ust4.6% respectively), adverse reactions in 9 pts (5%; Eta 7, 3%, Ada 3.2%), inefficacy in13 pts (7.2%; Eta 6.3%, Ada 8.1%, Ust 9.1%). 24-months survival rate was lower withEta, but not significantly because of poor sample size (HR 1.12- 95%CI 0.22-5.7; P¼.9).
Conclusions: The results obtained demonstrate biologics effectiveness in thetreatment of Pso in terms of clinical remission that allowed therapy discontinuation.A good long term global retention has been documented. Adherence was insteadinfluenced by adverse reactions and inefficacy appearance. Data highlight somefactors that may determine therapeutic failure of biological drugs in Pso pts,but these findings need further confirmation in larger population, with a longerfollow-up.
cial support: None identified.
Commer13
P7076Ruxolitinib-associated exfoliative dermatitis
John Fournier, MD, Roger Williams Medical Center, Deparment of Dermatologyand Skin Surgery, Providence, RI, United States; Catherine Breen, MD, RogerWilliams Medical Center, Department of Dermatology and Skin Surgery,Providence, RI, United States; Linda Zhou, MD, Roger Williams Medical Center,Department of Dermatology and Skin Surgery, Providence, RI, United States;Satori Iwamoto, MD, PhD, Roger Williams Medical Center, Department ofDermatology and Skin Surgery, Providence, RI, United States
A 61-year-old male with a 15-year history of myelofibrosis presented to theemergency room with a 1-week history of leg swelling, shortness of breath, andrash. The patient was subsequently admitted to the hospital with lower leg edema,anemia, and rash. Physical examination revealed erythematous macules and 2- to3-mm erythematous papules on the trunk and upper and lower extremities. Overthe next several days the morbilliform rash evolved into widespread confluenterythema over the trunk and extremities. A 3-mm punch biopsy was done on the leftarm. Superficial and deep perivascular granulomatous inflammation composed oflymphocytes, histiocytes, rare foreign body giant cells, and scattered eosinophilswas seen on biopsy. Clinicopathologic correlation supported a drug reaction.Ruxolitinib was tapered over the next several weeks. The patient was also treatedwith the aggressive use of emollients, as well as triamcinolone 0.1% cream to thetrunk, desonide 0.05% cream to the face, and an oral prednisone taper. Significantimprovement, namely reduced erythema and diminished scale, was seen within1 week of the onset of treatment. There was near resolution of the exfoliativedermatitis several weeks after discharge from the hospital. Three weeks before theappearance of the morbilliform rash the patient began ruxolitinib for the treatmentof myelofibrosis. He had no other new medications within the previous 6 months.Ruxolitinib is a novel treatment approved for myelofibrosis in 2011. Ruxolitinib is anorally bioavailable selective inhibitor of JAK1 and JAK2. A result of this selectiveinhibition is decreased levels of phosphorylated JAK2, and therefore decreasedactivity of the JAK/STAT pathway. To the best of our knowledge this is the firstreported case of ruxolitinib associated with rash or exfoliative dermatitis.
cial support: None identified.
CommerP6966The effect of folate supplementation on methotrexate efficacy in psoriasispatients
Amir Al-Dabagh, Wake Forest School of Medicine, Winston-Salem, NC, UnitedStates; Megan Kinney, MD, Wake Forest School of Medicine, Winston-Salem, NC,United States; Scott Davis, Wake Forest School of Medicine, Winston-Salem, NC,United States; Steve Feldman, MD, PhD, Wake Forest School of Medicine,Winston-Salem, NC, United States
Background: Methotrexate (MTX) is an effective treatment for psoriasis but its use islimited by its toxicity. Folate has been supplemented to reduce adverse events,although it may influence efficacy.
Purpose: The objective of this study was to review the literature involving the use offolate in patients (particular those with psoriasis) treated with MTX and analyzecurrent trends in folate use.
Methods: We searched PubMed from 1 May 1989 through 1 April 2012 using theterms ‘‘folic acid,’’ ‘‘folinic acid,’’ ‘‘supplementation,’’ and ‘‘methotrexate.’’ We alsoused the National Ambulatory Medical Care Survey database (NAMCS) to collect dataregarding trends in MTX use and folate supplementation by physicians in the UnitedStates from 1993 through 2009. We assessed data including number of MTX visits,rate of folate use, diagnoses, specialty of physician, and demographics of patients.We used linear regression to analyze the change in folic acid use over time.
Results: Twenty-nine published trials were included addressing folic acid supple-mentation with MTX; the majority found a benefit to folic acid supplementation, butthere were only 9 in psoriasis. Dermatologists were among the highest prescribersof MTX, and psoriasis was also commonly treated with MTX. Folic acid supplemen-tation significantly increased over this time period (P \ .0001). However,dermatologists ranked lowest for their folate use, coprescribing folate to only9.1% of MTX-treated patients.
Limitations: Data only included outpatient visits to nonefederally employedphysicians. Also, in contrast to rheumatoid arthritis, there is a scarcity of literaturedescribing the effect of folate on MTX toxicity and efficacy in psoriasis patients.
Conclusion: Dermatologists were the least likely specialists to supplement MTXwith folic acid. Additional studies with larger sample sizes are warranted to form anaccurate and complete assessment of folate’s influence on MTX toxicity and efficacyin psoriasis patients.
cial support: None identified.
CommerJ AM ACAD DERMATOL AB181
