- Email: [email protected]
What screening tests should be done? An evidence-based assessment of screening tests needed when using systemic agents to treat psoriasis
POSTER DISCUSSION SESSION 493—PSORIASIS I P17 Serious adverse drug events in infliximab-treated patients compared with the general and psoriasis populations J. M. Gelfand, MD, University of Pennsylvania, Philadelphia, PA, United States; J. Diels, MS, Johnson & Johnson Pharmaceutical Group Strategic Marketing, Raritan, NJ, United States; M. Bala, PhD, Centocor Research and Development, Inc., Malvern, PA, United States; S. Li, PhD, Centocor Research and Development, Inc., Malvern, PA, United States Objective: To compare rates of serious adverse events in infliximab (IFX)-treated patients in psoriasis clinical trials to the general and psoriasis populations. Methods: Data for the integrated safety analysis from clinical trials were obtained from randomized, placebo (PBO) controlled trials in moderate-to-severe psoriasis patients (EXPRESS, EXPRESS II, and SPIRIT). IFX doses included 3 to 5 mg/kg induction followed by scheduled or PRN maintenance (EXPRESS, EXPRESS II). Standardized mortality ratios (SMRs) compared mortality rates in IFX patients to what was expected in the US population. Mortality data for the psoriasis population were obtained from UK medical records databases, the General Practice Research Database (GPRD), and The Health Improvement Network (THIN). The MarketScan Claims Database was used to determine hospitalization and serious infection rates in the US psoriasis population. Results: In clinical trials, the total number of patients in the IFX and PBO grps were 1373 and 334, respectively. Number of deaths was 1 (0.09/100 patient-yrs [95% CI: 0.00,0.50]) and 0 (0/100 patient-yrs [95% CI: 0.00, 2.58]) for the combined IFX and PBO grps, respectively. SMR for IFX patients was 0.17; in comparison, SMR for a similar cohort of psoriasis patients in the GPRD and THIN databases were 1.13 (95% CI: 1.01, 1.27) and 1.26 (95% CI: 0.65, 2.21), respectively. Number of patients with $ 1 hospitalization was 83 (7.69/100 patient-yrs [95% CI: 6.13, 9.54]) and 8 (7.02/100 patient-yrs [95% CI: 3.03, 13.84]) for the combined IFX and PBO groups, respectively, and 8.05/100 patient-yrs (95% CI: 6.5,9.9) for the US psoriasis population. The number of patients with $ 1 serious infection was 20 (1.82/100 patient-yrs [95% CI: 1.11, 2.81]) and 2 (1.73/100 patient-yrs [95% CI: 0.21, 6.23]) for the combined IFX and PBO grps, respectively, and 1.40/100 patient-yrs (95% CI: 0.80, 2.27) for the US psoriasis population. The number of patients with $ 1 serious opportunistic infection was 2 (0.18/100 patient-yrs [95% CI: 0.02. 0.65]) and 0 (0/100 patient-yrs [95% CI: 0.00, 2.58]) for the combined IFX and PBO groups, respectively. Conclusions: Rates of mortality, hospitalizations, and serious infections were comparable between IFX and PBO patients in trials; the rate of opportunistic infections was slightly higher in the IFX group. Compared to the general and psoriasis populations, rates of mortality were lower in IFX patients; rates of serious infections and hospitalization rates were similar in IFX patients compared to the psoriasis population.
P19 Short- and long-term efficacy and safety of adalimumab in a pivotal phase III study in adult patients with moderate to severe chronic plaque psoriasis Alan Menter, MD, Texas Dermatology Research Institute, Dallas, TX, United States; Kim Papp, MD, Probity Medical Research, Waterloo, ON, Canada; Craig Leonardi, MD, Central Dermatology Inc., St. Louis, MO, United States; Lisa Frevert, MD, MPA, Abbott Laboratories, Parsippany, NJ, United States Objective: To evaluate short- and long-term clinical efficacy and safety of subcutaneously administered adalimumab in patients with moderate to severe chronic plaque psoriasis and to determine the proportion of patients losing a therapeutic response after withdrawal of long-term continuous adalimumab therapy. Methods: M03-656 is a 52-week, randomized, double-blind, placebo-controlled, multicenter, phase III study in patients with moderate to severe chronic plaque psoriasis (PASI $ 12, PGA of at least ‘‘moderate,’’ BSA $ 10%). The study consists of 3 treatment periods (A, B, and C) during which PASI 50/75/90/100 and PGA will be evaluated at weeks 4, 8, 12, 16, 24, 33, 40, 44, 48, and 52 using non-responder imputation. In Period A, patients are randomized 2:1 to receive adalimumab 80 mg at week 0 followed by 40 mg every other week (EOW) from week 1 through week 15 or placebo. Patients who achieve a $ PASI 75 at week 16 continue into the 17-week, open-label portion of the study, Period B. In Period B, patients receive adalimumab 40 mg EOW starting at week 17 through week 31. Placebo patients begin adalimumab 80 mg at week 16 followed by 40 mg EOW starting at week 17 through week 31. Patients who achieve at least a PASI 75 response at week 33 continue into Period C and are re-randomized, 1:1 to receive adalimumab or placebo, to compare the percentages of patients losing therapeutic response from week 33 to week 52. Patients who achieve PASI \75 response at week 16 and patients who achieve $ PASI 50 but PASI \75 at week 33 are eligible for continued treatment with adalimumab 40 mg EOW in a long-term, open-label extension study. Patients originally randomized in Period A to receive placebo and who are eligible for Period C continue to receive adalimumab 40 mg EOW in a blinded fashion. This study has 2 independent primary endpoints. The first primary endpoint is the proportion of patients achieving $ PASI 75 at week 16. The second primary endpoint is the proportion of patients losing therapeutic response between week s 33 and 52. Loss of adequate response is defined as: PASI \50 after week 33 relative to week 0 or a 6-point increase in the PASI score relative to week 33 (absolute change from week 33 improvement), whichever criterion is the more stringent for the patient. Six patient-reported outcome measures will be assessed, including DLQI and SF-36. Adverse events will be collected throughout the 52-week period. Results: One thousand two hundred and 12 patients were randomized to receive adalimumab at week 0. The mean age was 45 years (range, 18-82). Of 1212 patients, 804 (66%) were male and 1100 (91%) were white. 100% supported by Abbott.
Supported by Centocor, Inc.
P18 Utilization of narrow-band UVB light therapy and etanercept for the treatment of psoriasis (UNITE): Characteristics of PASI responders Leon Kircik, MD, Indiana University School of Medicine and Physicians Skin Care, Louisville, KY, United States; Craig Elmets, MD, University of Alabama at Birmingham, Birmingham, AL, United States; Alan Menter, MD, Baylor University Medical Center, Dallas, TX, United States; John Koo, MD, University of California at San Francisco, San Francisco, CA, United States Clinical trials in psoriasis often use the Psoriasis Area and Severity Index (PASI) 75 (indicating a 75% or greater improvement from baseline in PASI score) as a measure of response to therapy. PASI scores range from 0 to 72 on a severity scale, with higher scores indicating worse disease. Because of the high rate of complete psoriasis clearance—as measured by attainment of PASI 100 responses—in the Utilization of NB-UVB Light Therapy and Etanercept for the Treatment of Psoriasis (UNITE) trial, we are able to examine the characteristics of patients with severe psoriasis who achieved these higher response rates when receiving the combination of etanercept with NB-UVB. Adult patients with chronic plaque psoriasis and PASI score of 15 or greater at baseline received 50 mg etanercept twice-weekly (BIW) in combination with NB-UVB 3 times-weekly (TIW) for 12 weeks in this open-label, single-arm study. The primary endpoint was the proportion of patients achieving a PASI 75 response at week 12, while other analyses included the proportions of patients achieving PASI 90 and PASI 100. Analyses included all patients who received at least 1 dose of etanercept and NB-UVB phototherapy; analyses were conducted using a lastobservation-carried-forward approach. Of the 86 patients who received treatment, 26% achieved a PASI 100 response at week 12, 58% achieved PASI 90, and 85% achieved PASI 75. Potential relationships between patient characteristics and the likelihood of achieving a PASI 100 in this study will be presented, including comparisons of baseline and treatment characteristics of patients in the top quartile of PASI responders through 12 weeks of treatment with the bottom quartile of responders. Data from the UNITE study offer a unique opportunity to examine the characteristics of patients with psoriasis who achieved a complete psoriasis clearance with a combination of etanercept BIW and NB-UVB therapy TIW. Analyses are currently being performed, and data will be forthcoming. Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc, and by Wyeth Pharmaceuticals.
FEBRUARY 2007
P20 What screening tests should be done? An evidence-based assessment of screening tests needed when using systemic agents to treat psoriasis William Huang, MPH, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest University Health Sciences, Winston-Salem, NC, United States The development of new treatments for psoriasis provides dermatologists new ways to help control the disease but raise questions about what laboratory screening tests are required. As of yet, there is no consensus or guideline for dermatologists to follow, and there may be misconceptions about the relative need for screening tests. Current practice ranges from no testing to blanket screening panels. The purpose of this review are: (1) to systematically review the literature on the use of screening and monitoring tests when initiating and continuing patients on traditional systemic (methotrexate, cyclosporine, acitretin) and newer biologic (adalimumab, alefacept, efalizumab, etanercept, infliximab) treatments for moderate to severe psoriasis or psoriatic arthritis AND (2) To develop practical guidelines for dermatologists on which to base screening tests performed for these systemic treatments. We searched the Cochrane Collaborative database (including the Cochrane Database of Systematic Reviews [Cochrane Reviews] and the Cochrane Central Register of Controlled Trials [Clinical Trials]) and the MEDLINE database using Medical Subject Headings (MeSH or MH) as search terms when available or key words when appropriate. We compiled published data on risk and risk assessment related to systemic psoriasis treatments, used expert opinion where appropriate when published clinical data is not adequately informative, and assigned evidence grades for various screening tests based on standard methods of the US Preventive Services Task Force (USPSTF). Finally, we developed a series of practical flowcharts for following patients on the different systemic medications. This study was supported by a grant from Abbott Laboratories.
J AM ACAD DERMATOL
AB5
P19 Short- and long-term efficacy and safety of adalimumab in a pivotal phase III study in adult patients with moderate to severe chronic plaque psoriasis Alan Menter, MD, Texas Dermatology Research Institute, Dallas, TX, United States; Kim Papp, MD, Probity Medical Research, Waterloo, ON, Canada; Craig Leonardi, MD, Central Dermatology Inc., St. Louis, MO, United States; Lisa Frevert, MD, MPA, Abbott Laboratories, Parsippany, NJ, United States Objective: To evaluate short- and long-term clinical efficacy and safety of subcutaneously administered adalimumab in patients with moderate to severe chronic plaque psoriasis and to determine the proportion of patients losing a therapeutic response after withdrawal of long-term continuous adalimumab therapy. Methods: M03-656 is a 52-week, randomized, double-blind, placebo-controlled, multicenter, phase III study in patients with moderate to severe chronic plaque psoriasis (PASI $ 12, PGA of at least ‘‘moderate,’’ BSA $ 10%). The study consists of 3 treatment periods (A, B, and C) during which PASI 50/75/90/100 and PGA will be evaluated at weeks 4, 8, 12, 16, 24, 33, 40, 44, 48, and 52 using non-responder imputation. In Period A, patients are randomized 2:1 to receive adalimumab 80 mg at week 0 followed by 40 mg every other week (EOW) from week 1 through week 15 or placebo. Patients who achieve a $ PASI 75 at week 16 continue into the 17-week, open-label portion of the study, Period B. In Period B, patients receive adalimumab 40 mg EOW starting at week 17 through week 31. Placebo patients begin adalimumab 80 mg at week 16 followed by 40 mg EOW starting at week 17 through week 31. Patients who achieve at least a PASI 75 response at week 33 continue into Period C and are re-randomized, 1:1 to receive adalimumab or placebo, to compare the percentages of patients losing therapeutic response from week 33 to week 52. Patients who achieve PASI \75 response at week 16 and patients who achieve $ PASI 50 but PASI \75 at week 33 are eligible for continued treatment with adalimumab 40 mg EOW in a long-term, open-label extension study. Patients originally randomized in Period A to receive placebo and who are eligible for Period C continue to receive adalimumab 40 mg EOW in a blinded fashion. This study has 2 independent primary endpoints. The first primary endpoint is the proportion of patients achieving $ PASI 75 at week 16. The second primary endpoint is the proportion of patients losing therapeutic response between week s 33 and 52. Loss of adequate response is defined as: PASI \50 after week 33 relative to week 0 or a 6-point increase in the PASI score relative to week 33 (absolute change from week 33 improvement), whichever criterion is the more stringent for the patient. Six patient-reported outcome measures will be assessed, including DLQI and SF-36. Adverse events will be collected throughout the 52-week period. Results: One thousand two hundred and 12 patients were randomized to receive adalimumab at week 0. The mean age was 45 years (range, 18-82). Of 1212 patients, 804 (66%) were male and 1100 (91%) were white. 100% supported by Abbott.
Supported by Centocor, Inc.
P18 Utilization of narrow-band UVB light therapy and etanercept for the treatment of psoriasis (UNITE): Characteristics of PASI responders Leon Kircik, MD, Indiana University School of Medicine and Physicians Skin Care, Louisville, KY, United States; Craig Elmets, MD, University of Alabama at Birmingham, Birmingham, AL, United States; Alan Menter, MD, Baylor University Medical Center, Dallas, TX, United States; John Koo, MD, University of California at San Francisco, San Francisco, CA, United States Clinical trials in psoriasis often use the Psoriasis Area and Severity Index (PASI) 75 (indicating a 75% or greater improvement from baseline in PASI score) as a measure of response to therapy. PASI scores range from 0 to 72 on a severity scale, with higher scores indicating worse disease. Because of the high rate of complete psoriasis clearance—as measured by attainment of PASI 100 responses—in the Utilization of NB-UVB Light Therapy and Etanercept for the Treatment of Psoriasis (UNITE) trial, we are able to examine the characteristics of patients with severe psoriasis who achieved these higher response rates when receiving the combination of etanercept with NB-UVB. Adult patients with chronic plaque psoriasis and PASI score of 15 or greater at baseline received 50 mg etanercept twice-weekly (BIW) in combination with NB-UVB 3 times-weekly (TIW) for 12 weeks in this open-label, single-arm study. The primary endpoint was the proportion of patients achieving a PASI 75 response at week 12, while other analyses included the proportions of patients achieving PASI 90 and PASI 100. Analyses included all patients who received at least 1 dose of etanercept and NB-UVB phototherapy; analyses were conducted using a lastobservation-carried-forward approach. Of the 86 patients who received treatment, 26% achieved a PASI 100 response at week 12, 58% achieved PASI 90, and 85% achieved PASI 75. Potential relationships between patient characteristics and the likelihood of achieving a PASI 100 in this study will be presented, including comparisons of baseline and treatment characteristics of patients in the top quartile of PASI responders through 12 weeks of treatment with the bottom quartile of responders. Data from the UNITE study offer a unique opportunity to examine the characteristics of patients with psoriasis who achieved a complete psoriasis clearance with a combination of etanercept BIW and NB-UVB therapy TIW. Analyses are currently being performed, and data will be forthcoming. Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc, and by Wyeth Pharmaceuticals.
FEBRUARY 2007
P20 What screening tests should be done? An evidence-based assessment of screening tests needed when using systemic agents to treat psoriasis William Huang, MPH, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest University Health Sciences, Winston-Salem, NC, United States The development of new treatments for psoriasis provides dermatologists new ways to help control the disease but raise questions about what laboratory screening tests are required. As of yet, there is no consensus or guideline for dermatologists to follow, and there may be misconceptions about the relative need for screening tests. Current practice ranges from no testing to blanket screening panels. The purpose of this review are: (1) to systematically review the literature on the use of screening and monitoring tests when initiating and continuing patients on traditional systemic (methotrexate, cyclosporine, acitretin) and newer biologic (adalimumab, alefacept, efalizumab, etanercept, infliximab) treatments for moderate to severe psoriasis or psoriatic arthritis AND (2) To develop practical guidelines for dermatologists on which to base screening tests performed for these systemic treatments. We searched the Cochrane Collaborative database (including the Cochrane Database of Systematic Reviews [Cochrane Reviews] and the Cochrane Central Register of Controlled Trials [Clinical Trials]) and the MEDLINE database using Medical Subject Headings (MeSH or MH) as search terms when available or key words when appropriate. We compiled published data on risk and risk assessment related to systemic psoriasis treatments, used expert opinion where appropriate when published clinical data is not adequately informative, and assigned evidence grades for various screening tests based on standard methods of the US Preventive Services Task Force (USPSTF). Finally, we developed a series of practical flowcharts for following patients on the different systemic medications. This study was supported by a grant from Abbott Laboratories.
J AM ACAD DERMATOL
AB5