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Intralesional injections of alefacept may predict systemic response to intramuscular alefacept: Results from a pilot study
Intralesional injections of alefacept may predict systemic response to intramuscular alefacept: Results from a pilot study
Necrolytic acral erythema responding to antiviral therapy and zinc supplementation
(Poster reference number 5042)
(Poster reference number 4651)
Faranak Kamangar, University of California, San Francisco, San Francisco, CA, United States; Eric Lee, MD, University of California, San Francisco, San Francisco, CA, United States; John Koo, MD, University of California, San Francisco, San Francisco, CA, United States; Kelly Park, MD, University of California, San Francisco, San Francisco, CA, United States; Kristine Busse, MD, University of California, San Francisco, San Francisco, CA, United States; Misha Heller, University of California, San Francisco, San Francisco, CA, United States; Tina Bhutani, MD, University of California, San Francisco, San Francisco, CA, United States Background: Alefacept was the first biologic to be approved by the FDA in 2003, has no evidence-based concern for serious adverse events, has one of the longest durations of therapeutic effect, and is the only biologic officially approved for intermittent use. It is the least used biologic agent due to its erratic efficacy and slow onset of action. Maximal efficacy is seen approximately 6 weeks following a full 12week course of the medication. Patients undergo the cost and inconvenience of 3 months of weekly intramuscular injections and then a prolonged follow-up phase before they can be deemed a responder or nonresponder. At that point, only about one in three patients actually achieve a PASI 75, making treatment with alefacept frustrating for both physicians and patients. In this study, we aimed to find a quick and easy predictive test to determine if someone would be a responder or a nonresponder to alefacept prior to initiating systemic treatment. We tested intralesional injections of alefacept to a small psoriatic target plaque and then correlated the intralesional response with subsequent clinical response to a full 12week course of the medication.
Bassel Mahmoud, MD, PhD, Henry Ford Hospital, Detroit, MI, United States; Henry Lim, MD, Henry Ford Hospital, Detroit, MI, United States
Methods: 14 patients completed the full 22 week protocol which consisted of 3 phases: (1) phase I: intralesional injection to a small psoriatic plaque followed by 2 weeks of observation and assessment of plaque improvement; (2) phase II: 12-week course of intramuscular alefacept—15 mg IM weekly; (3) phase III: 6-week followup observational period.
Background: Necrolytic acral erythema (NAE) is an uncommon, chronic, papulosquamous, and occasionally vesiculobullous eruption, first described in 1996 as a cutaneous manifestation of hepatitis C virus (HCV) infection. NAE can be distinguished from the other necrolytic erythemas in its predilection for acral localization, lack of periorificial involvement, and association with hepatitis C infection. Case report: A 51-year-old Pakistani man with history of active HCV infection presented with seven months history of itchy thick, erythematous, hyperkeratotic, well-demarcated plaques on the dorsum of both feet and upper legs. Histopathologic examination showed psoriasiform dermatitis suggestive of necrolytic acral erythema. Patient was started on antiviral therapy in the form of pegylated interferon-alfa 2b and ribavirin. Serum zinc level was low (42 ug/dL, N: 60-130) and patient was given 220 mg of zinc sulfate PO twice daily. After 4 months of treatment, patient’s condition improved: HCV RNA became undetectable, liver functions improved, and serum zinc level increased. Skin lesions also responded well with decreased thickness and redness of the skin plaques, leaving postinflammatory hyperpigmentation. Discussion: NAE has been described as a cutaneous marker for HCV infection. Skin lesions poorly respond to topical steroids. Studies have shown that high concentrations of extracellular zinc suppress apoptosis by repressing the activation of endonuclease; and that deprivation of cellular zinc induces apoptosis both in vivo and in vitro. Furthermore, zinc supplementation has an antiinflammatory effect and enhances the results of interferon therapy in patients with HCV. Commercial support: None identified.
Results: There was a perfect correlation for this sample between intralesional responders/nonresponders and those with/without a 70% improvement in their overall PASI score from baseline leading to a significant association (P ¼ .0003). Conclusion: Although our sample size was small with no control arm, there was a perfect correlation—patients who responded to an intralesional injection of alefacept to a small plaque all achieved at least 70% improvement of their psoriasis after a 12-week course of the medication. None of the patients who did not respond to the intralesional injection reached 70% improvement of their PASI scores. This study provides a quick and easy predictive test to predetermine alefacept responders and nonresponders. Using this method may spare nonresponder patients the costs and inconvenience of multiple intramuscular injections and may help to make alefacept a more attractive treatment choice for physicians. Commercial support: This is an investigator initiated trial, funded by Astellas Pharmaceutical. Malignancy rates in the ustekinumab psoriasis clinical trial program: Update with up to 4 years of follow-up and comparisons to the general United States population
(Poster reference number 4777)
K. A. Papp, Probity Medical Research, Waterloo, Canada; J. C. Prinz, University of Munich, Munich, Germany; K. B. Gordon, University of Chicago Pritzker School of Medicine/NorthShore University Health System, Skokie, IL, United States; P. O. Szapary, Centocor Research and Development, Inc, Malvern, PA, United States Background: Malignancy rates were evaluated in ustekinumab clinical trials, now with up to 4 years of exposure, and compared with rates expected in the general US population. Methods: Rates of basal (BCC) and squamous cell (SCC) cancers or nonmelanoma skin cancers (NMSCs) and all other malignancies cumulatively and by year of exposure were evaluated in moderate to severe psoriasis patients in phase II and III trials. For malignancies other than NMSC, standardized incidence ratios (SIRs) compared observed malignancy rates in ustekinumab-treated patients to rates expected in the US population adjusted for age, sex and race based on data in the National Institutes of Health SEER database (2009). Results: 3117 patients were treated with ustekinumab with 6791 patient-years of follow-up (PY) for up to 4 years (2261, 1286, and 619 patients treated for $ 2, $ 3, and $ 4 years, respectively). Incidence of NMSC/100PY for ustekinumab 45 and 90 mg was 0.70 (95% CI, 0.43-1.09) and 0.53 (95% CI, 0.33-0.82), respectively; 41cases were observed (34 BCC and 10 SCC skin cancers [BCC:SCC, 3:1]). Incidences/100PY of NMSC by year evaluated were 0.94 (95% CI, 0.60-1.40) Year 1, 0.49 (95% CI, 0.21-0.96) Year 2, 0.41 (95% CI, 0.15-0.88) Year 3, and 0.27 (95% CI, 0.05-0.78) Year 4. Incidence/100PY of other malignancies for ustekinumab 45 and 90 mg was 0.63 (95% CI, 0.37-1.00) and 0.61 (95% CI, 0.39-0.91), respectively; 42 cases were observed and included ($ 2 cases) prostate, breast, melanoma in situ, colorectal, renal, head and neck, bladder, and leukemia. Respective rates of other malignancies were 0.39 (95% CI, 0.19-0.72) Year 1, 0.97 (95% CI, 0.56-1.58) Year 2, 0.34 (95% CI, 0.11-0.79) Year 3, 0.97 (95% CI, 0.49-1.74) Year 4. Rate of other malignancies reported in ustekinumab-treated patients was comparable to that expected in the general population (SIR ¼ 1.06 [95% CI, 0.76-1.43]).
Observation of the behavior of cell-mediated immunity in psoriatic patients treated with ustekinumab: Early results
(Poster reference number 5489)
Giovanna Malara, MD, Dermatology Department, Papardo Hospital, Messina, Italy; Elena Giunta, MD, Virology Department, Messina, Italy; Michele Lo Re, MD, Dermatology Department, Papardo Hospital, Messina, Italy
Conclusion: Rates of NMSC and other malignancies have remained stable compared with earlier analyses without an apparent dose effect. The observed malignancy rate was consistent with the expected rate in the general US population in the SEER database. Analyses with 5 years of follow-up are planned to continue examining the impact of IL-12/23 blockade on malignancy rates.
Psoriasis is a very common condition affecting approximately 2% of the general population, and is considered to be ‘‘T cellemediated dependent.’’ Several recent studies have shown that interleukin (IL) 12 and 23 have a central role in the development and maintenance of psoriatic lesions; for this reason a new biologic drug called ustekinumab has recently been created targeting p40, a subunit common to both IL-12 and IL-23. We carried out two different tests on a group of patients receiving ustikinumab. First, the assessment of the cell-mediated immune response in blood samples taken at weeks 0, 4, and 16 of treatment in order to detect leukocyte subsets such as CD3+, CD4+, CD8+, CD19+, NK, and CD4 na€ıve and memory. Second, biopsies of both healthy and affected skin were taken at the same time intervals to determine the existence/quantity of CD3, CD4, and CD8. Both the above mentioned tests evaluate the possible modification of cell-mediated immunity in patients undergoing treatment. The authors discuss the preliminary outcomes of this study.
Commercial support: Sponsored by Centocor Research and Development, Inc.
Commercial support: None identified.
AB196
J AM ACAD DERMATOL
APRIL 2012
Necrolytic acral erythema responding to antiviral therapy and zinc supplementation
(Poster reference number 5042)
(Poster reference number 4651)
Faranak Kamangar, University of California, San Francisco, San Francisco, CA, United States; Eric Lee, MD, University of California, San Francisco, San Francisco, CA, United States; John Koo, MD, University of California, San Francisco, San Francisco, CA, United States; Kelly Park, MD, University of California, San Francisco, San Francisco, CA, United States; Kristine Busse, MD, University of California, San Francisco, San Francisco, CA, United States; Misha Heller, University of California, San Francisco, San Francisco, CA, United States; Tina Bhutani, MD, University of California, San Francisco, San Francisco, CA, United States Background: Alefacept was the first biologic to be approved by the FDA in 2003, has no evidence-based concern for serious adverse events, has one of the longest durations of therapeutic effect, and is the only biologic officially approved for intermittent use. It is the least used biologic agent due to its erratic efficacy and slow onset of action. Maximal efficacy is seen approximately 6 weeks following a full 12week course of the medication. Patients undergo the cost and inconvenience of 3 months of weekly intramuscular injections and then a prolonged follow-up phase before they can be deemed a responder or nonresponder. At that point, only about one in three patients actually achieve a PASI 75, making treatment with alefacept frustrating for both physicians and patients. In this study, we aimed to find a quick and easy predictive test to determine if someone would be a responder or a nonresponder to alefacept prior to initiating systemic treatment. We tested intralesional injections of alefacept to a small psoriatic target plaque and then correlated the intralesional response with subsequent clinical response to a full 12week course of the medication.
Bassel Mahmoud, MD, PhD, Henry Ford Hospital, Detroit, MI, United States; Henry Lim, MD, Henry Ford Hospital, Detroit, MI, United States
Methods: 14 patients completed the full 22 week protocol which consisted of 3 phases: (1) phase I: intralesional injection to a small psoriatic plaque followed by 2 weeks of observation and assessment of plaque improvement; (2) phase II: 12-week course of intramuscular alefacept—15 mg IM weekly; (3) phase III: 6-week followup observational period.
Background: Necrolytic acral erythema (NAE) is an uncommon, chronic, papulosquamous, and occasionally vesiculobullous eruption, first described in 1996 as a cutaneous manifestation of hepatitis C virus (HCV) infection. NAE can be distinguished from the other necrolytic erythemas in its predilection for acral localization, lack of periorificial involvement, and association with hepatitis C infection. Case report: A 51-year-old Pakistani man with history of active HCV infection presented with seven months history of itchy thick, erythematous, hyperkeratotic, well-demarcated plaques on the dorsum of both feet and upper legs. Histopathologic examination showed psoriasiform dermatitis suggestive of necrolytic acral erythema. Patient was started on antiviral therapy in the form of pegylated interferon-alfa 2b and ribavirin. Serum zinc level was low (42 ug/dL, N: 60-130) and patient was given 220 mg of zinc sulfate PO twice daily. After 4 months of treatment, patient’s condition improved: HCV RNA became undetectable, liver functions improved, and serum zinc level increased. Skin lesions also responded well with decreased thickness and redness of the skin plaques, leaving postinflammatory hyperpigmentation. Discussion: NAE has been described as a cutaneous marker for HCV infection. Skin lesions poorly respond to topical steroids. Studies have shown that high concentrations of extracellular zinc suppress apoptosis by repressing the activation of endonuclease; and that deprivation of cellular zinc induces apoptosis both in vivo and in vitro. Furthermore, zinc supplementation has an antiinflammatory effect and enhances the results of interferon therapy in patients with HCV. Commercial support: None identified.
Results: There was a perfect correlation for this sample between intralesional responders/nonresponders and those with/without a 70% improvement in their overall PASI score from baseline leading to a significant association (P ¼ .0003). Conclusion: Although our sample size was small with no control arm, there was a perfect correlation—patients who responded to an intralesional injection of alefacept to a small plaque all achieved at least 70% improvement of their psoriasis after a 12-week course of the medication. None of the patients who did not respond to the intralesional injection reached 70% improvement of their PASI scores. This study provides a quick and easy predictive test to predetermine alefacept responders and nonresponders. Using this method may spare nonresponder patients the costs and inconvenience of multiple intramuscular injections and may help to make alefacept a more attractive treatment choice for physicians. Commercial support: This is an investigator initiated trial, funded by Astellas Pharmaceutical. Malignancy rates in the ustekinumab psoriasis clinical trial program: Update with up to 4 years of follow-up and comparisons to the general United States population
(Poster reference number 4777)
K. A. Papp, Probity Medical Research, Waterloo, Canada; J. C. Prinz, University of Munich, Munich, Germany; K. B. Gordon, University of Chicago Pritzker School of Medicine/NorthShore University Health System, Skokie, IL, United States; P. O. Szapary, Centocor Research and Development, Inc, Malvern, PA, United States Background: Malignancy rates were evaluated in ustekinumab clinical trials, now with up to 4 years of exposure, and compared with rates expected in the general US population. Methods: Rates of basal (BCC) and squamous cell (SCC) cancers or nonmelanoma skin cancers (NMSCs) and all other malignancies cumulatively and by year of exposure were evaluated in moderate to severe psoriasis patients in phase II and III trials. For malignancies other than NMSC, standardized incidence ratios (SIRs) compared observed malignancy rates in ustekinumab-treated patients to rates expected in the US population adjusted for age, sex and race based on data in the National Institutes of Health SEER database (2009). Results: 3117 patients were treated with ustekinumab with 6791 patient-years of follow-up (PY) for up to 4 years (2261, 1286, and 619 patients treated for $ 2, $ 3, and $ 4 years, respectively). Incidence of NMSC/100PY for ustekinumab 45 and 90 mg was 0.70 (95% CI, 0.43-1.09) and 0.53 (95% CI, 0.33-0.82), respectively; 41cases were observed (34 BCC and 10 SCC skin cancers [BCC:SCC, 3:1]). Incidences/100PY of NMSC by year evaluated were 0.94 (95% CI, 0.60-1.40) Year 1, 0.49 (95% CI, 0.21-0.96) Year 2, 0.41 (95% CI, 0.15-0.88) Year 3, and 0.27 (95% CI, 0.05-0.78) Year 4. Incidence/100PY of other malignancies for ustekinumab 45 and 90 mg was 0.63 (95% CI, 0.37-1.00) and 0.61 (95% CI, 0.39-0.91), respectively; 42 cases were observed and included ($ 2 cases) prostate, breast, melanoma in situ, colorectal, renal, head and neck, bladder, and leukemia. Respective rates of other malignancies were 0.39 (95% CI, 0.19-0.72) Year 1, 0.97 (95% CI, 0.56-1.58) Year 2, 0.34 (95% CI, 0.11-0.79) Year 3, 0.97 (95% CI, 0.49-1.74) Year 4. Rate of other malignancies reported in ustekinumab-treated patients was comparable to that expected in the general population (SIR ¼ 1.06 [95% CI, 0.76-1.43]).
Observation of the behavior of cell-mediated immunity in psoriatic patients treated with ustekinumab: Early results
(Poster reference number 5489)
Giovanna Malara, MD, Dermatology Department, Papardo Hospital, Messina, Italy; Elena Giunta, MD, Virology Department, Messina, Italy; Michele Lo Re, MD, Dermatology Department, Papardo Hospital, Messina, Italy
Conclusion: Rates of NMSC and other malignancies have remained stable compared with earlier analyses without an apparent dose effect. The observed malignancy rate was consistent with the expected rate in the general US population in the SEER database. Analyses with 5 years of follow-up are planned to continue examining the impact of IL-12/23 blockade on malignancy rates.
Psoriasis is a very common condition affecting approximately 2% of the general population, and is considered to be ‘‘T cellemediated dependent.’’ Several recent studies have shown that interleukin (IL) 12 and 23 have a central role in the development and maintenance of psoriatic lesions; for this reason a new biologic drug called ustekinumab has recently been created targeting p40, a subunit common to both IL-12 and IL-23. We carried out two different tests on a group of patients receiving ustikinumab. First, the assessment of the cell-mediated immune response in blood samples taken at weeks 0, 4, and 16 of treatment in order to detect leukocyte subsets such as CD3+, CD4+, CD8+, CD19+, NK, and CD4 na€ıve and memory. Second, biopsies of both healthy and affected skin were taken at the same time intervals to determine the existence/quantity of CD3, CD4, and CD8. Both the above mentioned tests evaluate the possible modification of cell-mediated immunity in patients undergoing treatment. The authors discuss the preliminary outcomes of this study.
Commercial support: Sponsored by Centocor Research and Development, Inc.
Commercial support: None identified.
AB196
J AM ACAD DERMATOL
APRIL 2012