Heavy Psoriasis Patients Benefit Especially from Weight-Based Treatments
In a poster introduced at the summer American Academy of Dermatology meeting, Mark Lebwohl, M.D., presented findings from four randomized, Phase III, placebo-controlled trials and an open-label study confirming that the injectable biologic drug efalizumab (Raptiva), the dosing of which is weight-based, had an acceptable safety and efficacy profile in the treatment of psoriasis in patients weighing over 200 pounds.
In these trials, efalizumab, a humanized anti-CD11a antibody approved for the systemic treatment of adult patients with chronic moderate to severe plaque psoriasis, showed similar safety and efficacy for patients under 200 pounds, as well as the historically more difficult-to-treat subpopulation of patients over that weight. Additionally, treatment response was maintained throughout continuous, long-term therapy of up to 3 years in both groups.
Dr. Lebwohl subsequently discussed with Skin & Aging the study and the special challenges involved in treating heavy patients — particularly those who are obese.
Dr. Lebwohl, who is Professor and Chairman, Department of Dermatology at Mount Sinai School of Medicine, explained that the weight-based dosing in efalizumab offered these patients — whose lesions, like their bodies, are apt to be larger in size than those of lower-weight patients — a more appropriate amount of medication than one-size-fits-all options.
However, for patients who are obese — and psoriasis patients are twice as likely to be overweight compared to the general population — additional issues apply.
“This patient subpopulation may have lesions in skin folds that limit the use of topical agents and phototherapy, as well as comorbidities such as cardiovascular and metabolic diseases that restrict the use of some systemic agents,” he said.
Asked whether obesity in fact predisposes patients to psoriasis, Dr. Lebwohl said that the clearer connection was to disease severity and the vicious cycle of patients’ controlling their weight in the face of the discomfort and embarrassment of the often-disfiguring condition.
“Obesity is clearly associated with more severe psoriasis. To make matters worse, overweight patients with psoriasis are less likely to be physically active and may overeat as a result of low self esteem and other emotional issues,” he maintained. This, he added, exacerbates both the psoriasis and comorbidities associated with heavy individuals such as hypertension, diabetes, or high cholesterol which may influence a dermatologist’s choice of therapy for this subpopulation.
Study Method
Objective. The primary objective of this analysis was to investigate potential associations between PASI response and body weight. It additionally sought to analyze the association between dropout rates, adverse events, and serious adverse events with patient weight.
Patient selection. A total of 2,674 patients with PASI score ≥12 and a body surface area (BSA) of psoriasis ≥10% were included in these analyses. For the analysis of efficacy by patient weight, there were 1,318 patients <200 pounds, and 1,356 patients ≥200 pounds. For the analysis of safety by patient weight, 715 (26.7%) had received placebo, and 1,959 (73.3%) had received efalizumab. The analysis was conducted for three groups of patients from seven studies (four Phase III, and three open-label).
Analysis of PASI response. All data were analyzed in 12-week periods. The numbers and percentages of responders at the end of weeks 12 and 24 were summarized for each patient group by weight using intent-to-treat (ITT) analysis and dropouts were considered non-responders. For the long-term study, the numbers and percentages of responder were summarized at the end of each 3-month (12-week) period until 36 months by weight using ITT analysis where the last observation for dropouts was carried forward.
Findings
Efficacy. At 12 weeks, efficacy was similar for the two groups with 28% of non-heavy patients and 25% of patients achieving PASI-75. At 24 weeks, efficacy was similar for the two groups with 42% of non-heavy patients and 43% of heavy patients achieving PASI-75.
Adverse events. The incidence of adverse events and rate of infection was similar in both patient groups. The most common adverse events observed were a symptom complex that included headache, chills, fever, nausea, and myalgia within 48 hours following the first two injections.
Conclusion
Since efalizumab is dosed by weight, the authors observe, it may produce a more linear response profile across patients of all weights. However, based on the consistency of response and safety profile demonstrated in their study, they conclude that regardless of patient weight, efalizumab appears to be an appropriate biologic agent for heavier patients who have plaque psoriasis.
Lebwohl M, Compton P, Caro I. Efficacy and Safety of Treating Psoriatic Patients ≥200 Pounds with Efalizumab.
The Obesity-Psoriasis Connection
On behalf of the the International Psoriasis Council, a group of experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity.
Authors of the report published in the British Medical Journal noted that the strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care.
This meeting reviewed the evidence-based literature and addressed how in the future, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.
Overwhelmingly, the data presented at this meeting support the linkage of psoriasis to both obesity and increased comorbidity risk.
Recommendations
The authors ultimately offered these recommendations for future investigations:
1. Prospective analyses of broadly representative psoriatic populations with well-matched control populations should examine the chronology of psoriasis-associated obesity and the metabolic syndrome.
2. Psoriasis and obesity (or the metabolic syndrome) should be mechanistically, and not solely epidemiologically, demonstrated as inter-related and perhaps mutually potentiating. With that in mind, future investigations should examine not only the absolute levels of adipocytokines but also how the endocrine⁄immunological functions of adipose tissue directly interact with the pathophysiology of psoriasis.
3. The effects of various systemic therapies for psoriasis, including traditional and biological agents, on comorbidity need to be prospectively measured.
4. The effects of obesity on therapy should be evaluated.
5. This question should be addressed: Do direct interventions regarding weight loss, smoking and alcohol reduction and better lipid, glucose and blood pressure control positively affect psoriasis severity?
6. Future prospective psoriasis studies and registries, at a minimum, should capture weight and ⁄or abdominal circumference, height, comprehensive metabolic laboratory measurements, fasting lipids, and blood pressure measurements, so that potential relationships between cardiac risk factors and effective therapy can be established.
7. Biomarkers of psoriatic inflammation must be identified in patients.
8. Future studies should examine for the presence of psoriatic arthritis, which is now known to affect between 10% and 40% of patients with psoriasis. Furthermore, the findings of such studies should stratify the results based on the presence or absence of joint disease or, more specifically, enthesopathy.
9. Studies on circulating vascular endothelial progenitor cells should be evaluated in psoriasis populations.
10. Studies on the genetics of psoriasis should include examination of mutations in genes known to regulate adipose tissue, obesity, and other facets of the metabolic syndrome.
11. To accomplish the above objectives, the authors’ final recommendation is that dermatologists collaborate with colleagues in endocrinology, genetics, cardiology, vascular biology, hepatology, pharmacology and rheumatology to promote psoriasis as an important healthcare policy issue.
Conclusion
Pointing out its association with obesity and significant systemic inflammation and that it affects 2% of the population worldwide, the authors surmise that psoriasis warrants a more comprehensive, prospective and multidisciplinary investigative approach to better to clarify the nature of its comorbidities — both epidemiologically and mechanistically.
Sterry W, Strober BE, Menter A. Obesity In Psoriasis: The Metabolic, Clinical and Therapeutic Implications. Report of an Interdisciplinary Conference and Review. Br J Dermatol. 2007 Oct;157(4):649-55.
Ustekinumab Reduces Psoriasis Severity
Ustekinumab, an experimental self-injectable biologic that targets interleukins, was reportedly found to substantially reduced the severity of psoriasis.
According to the study of some 1,230 patients, more than two-thirds of those taking ustekinumab achieved at least a 75% reduction in psoriasis at week 12 of treatment versus 4% with placebo.
Many analysts consider ustekinumab a potential follow-up to Centocor’s existing anti-inflammatory
drug, Remicade.
Centocor filed a Biologics License Application for ustekinumab in early December 2007. Approval could come some time this year.
Psoriasis Patients Found to Generate Greater Health Care Costs Than Others
A retrospective analysis using the PharMetrics database of patients with a diagnosis of psoriasis (ICD-9 code 696.1) from January 1, 2000, through June 30, 2005, determined that this group generated healthcare costs and resource consumption at a much higher rate than non-psoriasis patients.
Methods
The study cohort consisted of 178,411 patients. Among them, 31,033 patients had psoriasis, more than 50% were females, and mean age was 43 years. Moderate to severe psoriasis patients had received treatment with biologics, systemic therapy, or phototherapy.
To be included in the analysis, patient had to have been continuously enrolled for 6 months pre- and 12 months post-psoriasis diagnosis and to have had two distinct claims for psoriasis. The control group of patients without an inflammatory disease diagnosis was matched on age and gender.
Mean per-patient healthcare costs and resource utilization were calculated for patients in the year following their initial psoriasis diagnosis. Multivariable linear regression analysis was conducted to determine the impact of psoriasis on total healthcare costs, adjusting for age, gender, and comorbidities (Deyo-Charlson comorbidity index score).
Results
Psoriasis patients had higher comorbidities than the controls (0.66 vs. 0.44, p<0.0001). Mean annual total healthcare costs for all psoriasis patients were $4,987, compared with $2,667 (p<0.0001) for controls. Inpatient and physician costs constituted over 50% of the total healthcare costs in the psoriasis cohort. Total healthcare visits were almost two times higher for the psoriasis cohort compared with the controls (15.3 vs. 7.5, p<0.0001). Physician office visits constituted 78% of the resource utilization in the psoriasis cohort.
In this study, 20.5% of the patients had moderate to severe psoriasis; moderate to severe psoriasis patients had three times higher mean total healthcare costs ($7,632 vs $2,376, p<0.0001) and mean total resource utilization (23.4 vs 6.7, p<0.0001) compared with controls.
After adjusting the regression analysis, psoriasis patients’ total healthcare costs were 175% higher than the controls. Patients with moderate to severe psoriasis had 251% higher costs compared with controls after adjusting the regression analysis.
Conclusions
Noting the high healthcare costs and resource consumption of psoriasis patients, the authors called for additional studies to assess differences in quality of life and health outcomes related to specific treatments for patients with psoriasis.
Dabbous O, Thompson HC, Meissner B, Rahman MI. Impact of Psoriasis on Healthcare Costs and Resource Utilization in Patients Compared to Patients Without Psoriasis from a Payer Perspective.
Infliximab Response Found to be Consistent Across Patients with Psoriasis
To assess the consistency of infliximab (Remicade) response among different subgroups of patients with moderate to severe psoriasis, the impact of gender, obesity, age, baseline psoriasis severity, concomitant psoriatic arthritis (PsA), or prior therapies on response to infliximab was studied in an integrated efficacy analysis.
Methods
Data from three randomized, placebo-controlled clinical trials (SPIRIT, EXPRESS and EXPRESS II) that evaluated the use of infliximab in patients with moderate to severe psoriasis were included in this integrated analysis.
Patients received placebo, infliximab 3 mg/kg, or infliximab 5 mg/kg at 0, 2 and 6 weeks. The common primary endpoint at week 10 was the proportion of patients achieving ≥75% improvement in the Psoriasis Area and Severity Index (PASI 75) from baseline. Safety data through week 16 were pooled for analysis.
Results
Of the 1,462 patients included in this analysis, 70.6% and 79.3% in the infliximab 3 and 5 mg/kg groups, respectively, achieved at least a PASI 75 response at week 10, compared with 2.7% in the placebo group (both p<0.001). The proportions of patients achieving PASI 75 at week 10 were consistent in subgroups defined by baseline demographic characteristics (gender, age, body mass index) and also defined by baseline disease characteristics (PASI severity, body surface area, presence of psoriatic arthritis). Consistent results were also observed regardless of psoriasis therapeutic history. Infliximab treatment was generally well tolerated by the majority of study participants.
Conclusion
A consistently high level of clinical response to infliximab was demonstrated across subgroups defined by a variety of baseline demographic and disease characteristics in patients with psoriasis. Infliximab was similarly effective regardless of previous use of phototherapy or major conventional systemic therapies.
The Obese Subgroup
Integrated efficacy analyses were conducted to determine the consistency of response to infliximab among different subgroups of patients — including those who were obese — with moderate to severe psoriasis within these three studies.
Responses by gender and baseline age (<40 years, ≥40 years) and by baseline body mass index (BMI; <25, ≥25 to <30, ≥3)were recorded and evaluated.
Reich K, Menter A, Plotnick M, Guzzo C, Li S, Gottlieb AB. Consistency of Infliximab Response Across Subgroups of Patients With Psoriasis: Integrated Results From Randomized Clinical Trials.
Phase III Data Suggest Golimumab (CNTO 148) Significantly Improves Skin and Nails As Well as Arthritis in Patients with Psoriatic Arthritis
According to findings from the largest Phase III biologic study ever completed in subjects with psoriatic arthritis, patients with active psoriatic arthritis receiving monthly subcutaneous injections of golimumab (CNTO 148), a next-generation human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, experienced significant and sustained improvements in the joint and skin manifestations of the disease, achieving primary and secondary endpoints
This 24-week efficacy and safety results of the randomized, placebo-controlled GO-REVEAL study showed that at week 14 of the 405-patient study in subjects with active psoriatic arthritis, 51% of patients receiving golimumab
50 mg and 45% of patients receiving golimumab 100 mg experienced at least 20% improvement in arthritis signs and symptoms (ACR 20) compared with 9% of patients receiving placebo (p < 0.001 for both comparisons). It further demonstrated that patients treated with golimumab, maintained significant improvements in arthritis through week 24. These patients also showed substantial and sustained improvements in skin and nail psoriatic disease (as measured by a 75% reduction in Psoriasis Area and Severity Index [PASI 75] in patients with baseline body surface area with psoriasis of at least 3%, and the Nail Psoriasis Severity Index [NAPSI]).
Key Data Points
Skin symptoms. At 14 weeks, 40% and 58% of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieved at least 75% improvement (PASI 75) in the skin symptoms of PsA. At 6 months, 56% and 66% of patients in the respective golimumab treatment groups achieved PASI 75.
Arthritis symptoms. At 14 weeks, 51% of patients receiving golimumab 50 mg and 45% of patients receiving golimumab 100 mg achieved at least a 20% reduction in signs and symptoms of PsA; 30% and 28% of patients in the respective golimumab treatment groups achieved at least a 50% reduction. These results persisted through 6 months.
The REVEAL Study
Objective. To assess the efficacy and safety of golimumab in reducing signs and symptoms of active PsA and associated skin and nail disease.
Patient Information. Enrolled population included 405 adults with at least three or more swollen and tender joints. Across placebo and golimumab groups at baseline, the mean age ranged from 46 to 48 years, the mean swollen/tender joint counts were 12-14/22-24, the mean HAQ scores were 1.0 to 1.1, and the mean PASI scores were 8.4 to 11.1. Placebo and golimumab groups were balanced for baseline demographic and disease characteristics.
Method
Patients were randomly assigned to receive subcutaneous injections of placebo (placebo) or golimumab (50 or 100 mg) at weeks 0, 4, 8, 12, 16, and 20.
Patients with inadequate arthritis response at week 16 were switched in a blinded manner to golimumab 50 mg (placebo patients) or golimumab 100 mg (golimumab 50 and 100 patients).
Placebo and golimumab 50 mg patients had their last observation prior to change in treatment carried forward for the week-24 efficacy analyses; the observed values at week 24 were used for golimumab 100 patients.
Concomitant methotrexate was allowed but not required.
The primary endpoint (ACR20 at week 14) was analyzed by the Cochran-Mantel-Haenszel test with stratification by methotrexate use.
Results
Efficacy. Golimumab was found to be significantly better than placebo in improving signs and symptoms of PsA .
The two golimumab doses were comparable in efficacy, and patients switching from golimumab 50 to 100 had minimal improvement from week 16 to 24.
Concomitant methotrexate did not affect efficacy.
Safety. Golimumab was generally well tolerated, with 2.4% of golimumab patients experiencing serious adverse events (SAEs) through week 24 vs. 6.2% of placebo patients. Injection site reactions were rare and occurred in 4.8% of golimumab and 2.7% of placebo patients. Antibodies to golimumab were detected in 4.6% of golimumab patients through week 24. One SAE of malignancy (prostate cancer) and two cases of basal cell carcinoma were reported in golimumab patients. There were no reports of tuberculosis or opportunistic infections.
Conclusion
In patients with active PsA, golimumab 50 and 100 mg for 24 weeks significantly improved active PsA and psoriatic skin and nail disease through week 24 and was generally well tolerated.
Abbott’s ABT-874 Found Highly Effective For Psoriasis Even After Discontinuation
A Phase II study evaluating the effectiveness of Abbott’s investigational anti-IL-12/23 antibody ABT-874 showed that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy. In the study, patients who achieved 75% improvement in psoriasis signs and symptoms (PASI 75) at 12 weeks stopped receiving ABT-874. At 24 weeks, more than two-thirds of these patients maintained at least 50% improvement (PASI 50).
Study Background and Results
Initial Phase II Study
In a 12-week, double-blind, placebo-controlled study, 180 patients with moderate to severe psoriasis were randomized evenly to six treatment groups: a single, subcutaneous 200-mg injection of ABT-874 at week zero; 100 mg every other week for 12 weeks; 200 mg weekly for 4 weeks; 200 mg every other week for 12 weeks; 200 mg weekly for 12 weeks; or matching placebo. The primary study endpoint was the proportion of patients achieving 75% improvement in the degree and severity of skin lesions after 12 weeks, measured by the Psoriasis Area and Severity Index (PASI).
At least 90% of patients achieved PASI 75 at week 12 in all ABT-874 treatment groups except the single-dose group (200 mg at week zero). (Results were, respectively, 63%, 93%, 90%, 93%, and 90%, vs. 3% of those receiving placebo; p<0.001 for all groups.) Also, in the same four treatment groups, more than half of patients achieved 90% improvement in skin clearance (results were, respectively, 17%, 53%, 63%, 77%, 53%, vs. 0% of those receiving placebo; p<0.001 for all groups except the single-dose group, 200 mg at week 0).
Continuation Study
A Phase II follow-up study evaluating the effectiveness of ABT-874 in patients with moderate to severe psoriasis found that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy.
In the continuation of the Phase II study, treatment with ABT-874 was discontinued in patients who met the primary endpoint. Maintenance of PASI response was evaluated through week 48.
Reported results from 24 weeks. Substantial percentages of PASI 75 responders in the active treatments arms had maintained ≥ PASI 50 responses. Results were 68% (13 out of 19 patients), 71% (20 of 28), 81% (22 of 27), 89% (25 of 28), and 85% (23 of 27) in the five ABT-874 dosing groups, respectively.
Adverse events. The most common adverse events observed were injection-site reactions, nasopharyngitis, upper respiratory infections, and response that is not addressed by any therapy available today.
Heavy Psoriasis Patients Benefit Especially from Weight-Based Treatments
In a poster introduced at the summer American Academy of Dermatology meeting, Mark Lebwohl, M.D., presented findings from four randomized, Phase III, placebo-controlled trials and an open-label study confirming that the injectable biologic drug efalizumab (Raptiva), the dosing of which is weight-based, had an acceptable safety and efficacy profile in the treatment of psoriasis in patients weighing over 200 pounds.
In these trials, efalizumab, a humanized anti-CD11a antibody approved for the systemic treatment of adult patients with chronic moderate to severe plaque psoriasis, showed similar safety and efficacy for patients under 200 pounds, as well as the historically more difficult-to-treat subpopulation of patients over that weight. Additionally, treatment response was maintained throughout continuous, long-term therapy of up to 3 years in both groups.
Dr. Lebwohl subsequently discussed with Skin & Aging the study and the special challenges involved in treating heavy patients — particularly those who are obese.
Dr. Lebwohl, who is Professor and Chairman, Department of Dermatology at Mount Sinai School of Medicine, explained that the weight-based dosing in efalizumab offered these patients — whose lesions, like their bodies, are apt to be larger in size than those of lower-weight patients — a more appropriate amount of medication than one-size-fits-all options.
However, for patients who are obese — and psoriasis patients are twice as likely to be overweight compared to the general population — additional issues apply.
“This patient subpopulation may have lesions in skin folds that limit the use of topical agents and phototherapy, as well as comorbidities such as cardiovascular and metabolic diseases that restrict the use of some systemic agents,” he said.
Asked whether obesity in fact predisposes patients to psoriasis, Dr. Lebwohl said that the clearer connection was to disease severity and the vicious cycle of patients’ controlling their weight in the face of the discomfort and embarrassment of the often-disfiguring condition.
“Obesity is clearly associated with more severe psoriasis. To make matters worse, overweight patients with psoriasis are less likely to be physically active and may overeat as a result of low self esteem and other emotional issues,” he maintained. This, he added, exacerbates both the psoriasis and comorbidities associated with heavy individuals such as hypertension, diabetes, or high cholesterol which may influence a dermatologist’s choice of therapy for this subpopulation.
Study Method
Objective. The primary objective of this analysis was to investigate potential associations between PASI response and body weight. It additionally sought to analyze the association between dropout rates, adverse events, and serious adverse events with patient weight.
Patient selection. A total of 2,674 patients with PASI score ≥12 and a body surface area (BSA) of psoriasis ≥10% were included in these analyses. For the analysis of efficacy by patient weight, there were 1,318 patients <200 pounds, and 1,356 patients ≥200 pounds. For the analysis of safety by patient weight, 715 (26.7%) had received placebo, and 1,959 (73.3%) had received efalizumab. The analysis was conducted for three groups of patients from seven studies (four Phase III, and three open-label).
Analysis of PASI response. All data were analyzed in 12-week periods. The numbers and percentages of responders at the end of weeks 12 and 24 were summarized for each patient group by weight using intent-to-treat (ITT) analysis and dropouts were considered non-responders. For the long-term study, the numbers and percentages of responder were summarized at the end of each 3-month (12-week) period until 36 months by weight using ITT analysis where the last observation for dropouts was carried forward.
Findings
Efficacy. At 12 weeks, efficacy was similar for the two groups with 28% of non-heavy patients and 25% of patients achieving PASI-75. At 24 weeks, efficacy was similar for the two groups with 42% of non-heavy patients and 43% of heavy patients achieving PASI-75.
Adverse events. The incidence of adverse events and rate of infection was similar in both patient groups. The most common adverse events observed were a symptom complex that included headache, chills, fever, nausea, and myalgia within 48 hours following the first two injections.
Conclusion
Since efalizumab is dosed by weight, the authors observe, it may produce a more linear response profile across patients of all weights. However, based on the consistency of response and safety profile demonstrated in their study, they conclude that regardless of patient weight, efalizumab appears to be an appropriate biologic agent for heavier patients who have plaque psoriasis.
Lebwohl M, Compton P, Caro I. Efficacy and Safety of Treating Psoriatic Patients ≥200 Pounds with Efalizumab.
The Obesity-Psoriasis Connection
On behalf of the the International Psoriasis Council, a group of experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity.
Authors of the report published in the British Medical Journal noted that the strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care.
This meeting reviewed the evidence-based literature and addressed how in the future, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.
Overwhelmingly, the data presented at this meeting support the linkage of psoriasis to both obesity and increased comorbidity risk.
Recommendations
The authors ultimately offered these recommendations for future investigations:
1. Prospective analyses of broadly representative psoriatic populations with well-matched control populations should examine the chronology of psoriasis-associated obesity and the metabolic syndrome.
2. Psoriasis and obesity (or the metabolic syndrome) should be mechanistically, and not solely epidemiologically, demonstrated as inter-related and perhaps mutually potentiating. With that in mind, future investigations should examine not only the absolute levels of adipocytokines but also how the endocrine⁄immunological functions of adipose tissue directly interact with the pathophysiology of psoriasis.
3. The effects of various systemic therapies for psoriasis, including traditional and biological agents, on comorbidity need to be prospectively measured.
4. The effects of obesity on therapy should be evaluated.
5. This question should be addressed: Do direct interventions regarding weight loss, smoking and alcohol reduction and better lipid, glucose and blood pressure control positively affect psoriasis severity?
6. Future prospective psoriasis studies and registries, at a minimum, should capture weight and ⁄or abdominal circumference, height, comprehensive metabolic laboratory measurements, fasting lipids, and blood pressure measurements, so that potential relationships between cardiac risk factors and effective therapy can be established.
7. Biomarkers of psoriatic inflammation must be identified in patients.
8. Future studies should examine for the presence of psoriatic arthritis, which is now known to affect between 10% and 40% of patients with psoriasis. Furthermore, the findings of such studies should stratify the results based on the presence or absence of joint disease or, more specifically, enthesopathy.
9. Studies on circulating vascular endothelial progenitor cells should be evaluated in psoriasis populations.
10. Studies on the genetics of psoriasis should include examination of mutations in genes known to regulate adipose tissue, obesity, and other facets of the metabolic syndrome.
11. To accomplish the above objectives, the authors’ final recommendation is that dermatologists collaborate with colleagues in endocrinology, genetics, cardiology, vascular biology, hepatology, pharmacology and rheumatology to promote psoriasis as an important healthcare policy issue.
Conclusion
Pointing out its association with obesity and significant systemic inflammation and that it affects 2% of the population worldwide, the authors surmise that psoriasis warrants a more comprehensive, prospective and multidisciplinary investigative approach to better to clarify the nature of its comorbidities — both epidemiologically and mechanistically.
Sterry W, Strober BE, Menter A. Obesity In Psoriasis: The Metabolic, Clinical and Therapeutic Implications. Report of an Interdisciplinary Conference and Review. Br J Dermatol. 2007 Oct;157(4):649-55.
Ustekinumab Reduces Psoriasis Severity
Ustekinumab, an experimental self-injectable biologic that targets interleukins, was reportedly found to substantially reduced the severity of psoriasis.
According to the study of some 1,230 patients, more than two-thirds of those taking ustekinumab achieved at least a 75% reduction in psoriasis at week 12 of treatment versus 4% with placebo.
Many analysts consider ustekinumab a potential follow-up to Centocor’s existing anti-inflammatory
drug, Remicade.
Centocor filed a Biologics License Application for ustekinumab in early December 2007. Approval could come some time this year.
Psoriasis Patients Found to Generate Greater Health Care Costs Than Others
A retrospective analysis using the PharMetrics database of patients with a diagnosis of psoriasis (ICD-9 code 696.1) from January 1, 2000, through June 30, 2005, determined that this group generated healthcare costs and resource consumption at a much higher rate than non-psoriasis patients.
Methods
The study cohort consisted of 178,411 patients. Among them, 31,033 patients had psoriasis, more than 50% were females, and mean age was 43 years. Moderate to severe psoriasis patients had received treatment with biologics, systemic therapy, or phototherapy.
To be included in the analysis, patient had to have been continuously enrolled for 6 months pre- and 12 months post-psoriasis diagnosis and to have had two distinct claims for psoriasis. The control group of patients without an inflammatory disease diagnosis was matched on age and gender.
Mean per-patient healthcare costs and resource utilization were calculated for patients in the year following their initial psoriasis diagnosis. Multivariable linear regression analysis was conducted to determine the impact of psoriasis on total healthcare costs, adjusting for age, gender, and comorbidities (Deyo-Charlson comorbidity index score).
Results
Psoriasis patients had higher comorbidities than the controls (0.66 vs. 0.44, p<0.0001). Mean annual total healthcare costs for all psoriasis patients were $4,987, compared with $2,667 (p<0.0001) for controls. Inpatient and physician costs constituted over 50% of the total healthcare costs in the psoriasis cohort. Total healthcare visits were almost two times higher for the psoriasis cohort compared with the controls (15.3 vs. 7.5, p<0.0001). Physician office visits constituted 78% of the resource utilization in the psoriasis cohort.
In this study, 20.5% of the patients had moderate to severe psoriasis; moderate to severe psoriasis patients had three times higher mean total healthcare costs ($7,632 vs $2,376, p<0.0001) and mean total resource utilization (23.4 vs 6.7, p<0.0001) compared with controls.
After adjusting the regression analysis, psoriasis patients’ total healthcare costs were 175% higher than the controls. Patients with moderate to severe psoriasis had 251% higher costs compared with controls after adjusting the regression analysis.
Conclusions
Noting the high healthcare costs and resource consumption of psoriasis patients, the authors called for additional studies to assess differences in quality of life and health outcomes related to specific treatments for patients with psoriasis.
Dabbous O, Thompson HC, Meissner B, Rahman MI. Impact of Psoriasis on Healthcare Costs and Resource Utilization in Patients Compared to Patients Without Psoriasis from a Payer Perspective.
Infliximab Response Found to be Consistent Across Patients with Psoriasis
To assess the consistency of infliximab (Remicade) response among different subgroups of patients with moderate to severe psoriasis, the impact of gender, obesity, age, baseline psoriasis severity, concomitant psoriatic arthritis (PsA), or prior therapies on response to infliximab was studied in an integrated efficacy analysis.
Methods
Data from three randomized, placebo-controlled clinical trials (SPIRIT, EXPRESS and EXPRESS II) that evaluated the use of infliximab in patients with moderate to severe psoriasis were included in this integrated analysis.
Patients received placebo, infliximab 3 mg/kg, or infliximab 5 mg/kg at 0, 2 and 6 weeks. The common primary endpoint at week 10 was the proportion of patients achieving ≥75% improvement in the Psoriasis Area and Severity Index (PASI 75) from baseline. Safety data through week 16 were pooled for analysis.
Results
Of the 1,462 patients included in this analysis, 70.6% and 79.3% in the infliximab 3 and 5 mg/kg groups, respectively, achieved at least a PASI 75 response at week 10, compared with 2.7% in the placebo group (both p<0.001). The proportions of patients achieving PASI 75 at week 10 were consistent in subgroups defined by baseline demographic characteristics (gender, age, body mass index) and also defined by baseline disease characteristics (PASI severity, body surface area, presence of psoriatic arthritis). Consistent results were also observed regardless of psoriasis therapeutic history. Infliximab treatment was generally well tolerated by the majority of study participants.
Conclusion
A consistently high level of clinical response to infliximab was demonstrated across subgroups defined by a variety of baseline demographic and disease characteristics in patients with psoriasis. Infliximab was similarly effective regardless of previous use of phototherapy or major conventional systemic therapies.
The Obese Subgroup
Integrated efficacy analyses were conducted to determine the consistency of response to infliximab among different subgroups of patients — including those who were obese — with moderate to severe psoriasis within these three studies.
Responses by gender and baseline age (<40 years, ≥40 years) and by baseline body mass index (BMI; <25, ≥25 to <30, ≥3)were recorded and evaluated.
Reich K, Menter A, Plotnick M, Guzzo C, Li S, Gottlieb AB. Consistency of Infliximab Response Across Subgroups of Patients With Psoriasis: Integrated Results From Randomized Clinical Trials.
Phase III Data Suggest Golimumab (CNTO 148) Significantly Improves Skin and Nails As Well as Arthritis in Patients with Psoriatic Arthritis
According to findings from the largest Phase III biologic study ever completed in subjects with psoriatic arthritis, patients with active psoriatic arthritis receiving monthly subcutaneous injections of golimumab (CNTO 148), a next-generation human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, experienced significant and sustained improvements in the joint and skin manifestations of the disease, achieving primary and secondary endpoints
This 24-week efficacy and safety results of the randomized, placebo-controlled GO-REVEAL study showed that at week 14 of the 405-patient study in subjects with active psoriatic arthritis, 51% of patients receiving golimumab
50 mg and 45% of patients receiving golimumab 100 mg experienced at least 20% improvement in arthritis signs and symptoms (ACR 20) compared with 9% of patients receiving placebo (p < 0.001 for both comparisons). It further demonstrated that patients treated with golimumab, maintained significant improvements in arthritis through week 24. These patients also showed substantial and sustained improvements in skin and nail psoriatic disease (as measured by a 75% reduction in Psoriasis Area and Severity Index [PASI 75] in patients with baseline body surface area with psoriasis of at least 3%, and the Nail Psoriasis Severity Index [NAPSI]).
Key Data Points
Skin symptoms. At 14 weeks, 40% and 58% of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieved at least 75% improvement (PASI 75) in the skin symptoms of PsA. At 6 months, 56% and 66% of patients in the respective golimumab treatment groups achieved PASI 75.
Arthritis symptoms. At 14 weeks, 51% of patients receiving golimumab 50 mg and 45% of patients receiving golimumab 100 mg achieved at least a 20% reduction in signs and symptoms of PsA; 30% and 28% of patients in the respective golimumab treatment groups achieved at least a 50% reduction. These results persisted through 6 months.
The REVEAL Study
Objective. To assess the efficacy and safety of golimumab in reducing signs and symptoms of active PsA and associated skin and nail disease.
Patient Information. Enrolled population included 405 adults with at least three or more swollen and tender joints. Across placebo and golimumab groups at baseline, the mean age ranged from 46 to 48 years, the mean swollen/tender joint counts were 12-14/22-24, the mean HAQ scores were 1.0 to 1.1, and the mean PASI scores were 8.4 to 11.1. Placebo and golimumab groups were balanced for baseline demographic and disease characteristics.
Method
Patients were randomly assigned to receive subcutaneous injections of placebo (placebo) or golimumab (50 or 100 mg) at weeks 0, 4, 8, 12, 16, and 20.
Patients with inadequate arthritis response at week 16 were switched in a blinded manner to golimumab 50 mg (placebo patients) or golimumab 100 mg (golimumab 50 and 100 patients).
Placebo and golimumab 50 mg patients had their last observation prior to change in treatment carried forward for the week-24 efficacy analyses; the observed values at week 24 were used for golimumab 100 patients.
Concomitant methotrexate was allowed but not required.
The primary endpoint (ACR20 at week 14) was analyzed by the Cochran-Mantel-Haenszel test with stratification by methotrexate use.
Results
Efficacy. Golimumab was found to be significantly better than placebo in improving signs and symptoms of PsA .
The two golimumab doses were comparable in efficacy, and patients switching from golimumab 50 to 100 had minimal improvement from week 16 to 24.
Concomitant methotrexate did not affect efficacy.
Safety. Golimumab was generally well tolerated, with 2.4% of golimumab patients experiencing serious adverse events (SAEs) through week 24 vs. 6.2% of placebo patients. Injection site reactions were rare and occurred in 4.8% of golimumab and 2.7% of placebo patients. Antibodies to golimumab were detected in 4.6% of golimumab patients through week 24. One SAE of malignancy (prostate cancer) and two cases of basal cell carcinoma were reported in golimumab patients. There were no reports of tuberculosis or opportunistic infections.
Conclusion
In patients with active PsA, golimumab 50 and 100 mg for 24 weeks significantly improved active PsA and psoriatic skin and nail disease through week 24 and was generally well tolerated.
Abbott’s ABT-874 Found Highly Effective For Psoriasis Even After Discontinuation
A Phase II study evaluating the effectiveness of Abbott’s investigational anti-IL-12/23 antibody ABT-874 showed that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy. In the study, patients who achieved 75% improvement in psoriasis signs and symptoms (PASI 75) at 12 weeks stopped receiving ABT-874. At 24 weeks, more than two-thirds of these patients maintained at least 50% improvement (PASI 50).
Study Background and Results
Initial Phase II Study
In a 12-week, double-blind, placebo-controlled study, 180 patients with moderate to severe psoriasis were randomized evenly to six treatment groups: a single, subcutaneous 200-mg injection of ABT-874 at week zero; 100 mg every other week for 12 weeks; 200 mg weekly for 4 weeks; 200 mg every other week for 12 weeks; 200 mg weekly for 12 weeks; or matching placebo. The primary study endpoint was the proportion of patients achieving 75% improvement in the degree and severity of skin lesions after 12 weeks, measured by the Psoriasis Area and Severity Index (PASI).
At least 90% of patients achieved PASI 75 at week 12 in all ABT-874 treatment groups except the single-dose group (200 mg at week zero). (Results were, respectively, 63%, 93%, 90%, 93%, and 90%, vs. 3% of those receiving placebo; p<0.001 for all groups.) Also, in the same four treatment groups, more than half of patients achieved 90% improvement in skin clearance (results were, respectively, 17%, 53%, 63%, 77%, 53%, vs. 0% of those receiving placebo; p<0.001 for all groups except the single-dose group, 200 mg at week 0).
Continuation Study
A Phase II follow-up study evaluating the effectiveness of ABT-874 in patients with moderate to severe psoriasis found that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy.
In the continuation of the Phase II study, treatment with ABT-874 was discontinued in patients who met the primary endpoint. Maintenance of PASI response was evaluated through week 48.
Reported results from 24 weeks. Substantial percentages of PASI 75 responders in the active treatments arms had maintained ≥ PASI 50 responses. Results were 68% (13 out of 19 patients), 71% (20 of 28), 81% (22 of 27), 89% (25 of 28), and 85% (23 of 27) in the five ABT-874 dosing groups, respectively.
Adverse events. The most common adverse events observed were injection-site reactions, nasopharyngitis, upper respiratory infections, and response that is not addressed by any therapy available today.
Heavy Psoriasis Patients Benefit Especially from Weight-Based Treatments
In a poster introduced at the summer American Academy of Dermatology meeting, Mark Lebwohl, M.D., presented findings from four randomized, Phase III, placebo-controlled trials and an open-label study confirming that the injectable biologic drug efalizumab (Raptiva), the dosing of which is weight-based, had an acceptable safety and efficacy profile in the treatment of psoriasis in patients weighing over 200 pounds.
In these trials, efalizumab, a humanized anti-CD11a antibody approved for the systemic treatment of adult patients with chronic moderate to severe plaque psoriasis, showed similar safety and efficacy for patients under 200 pounds, as well as the historically more difficult-to-treat subpopulation of patients over that weight. Additionally, treatment response was maintained throughout continuous, long-term therapy of up to 3 years in both groups.
Dr. Lebwohl subsequently discussed with Skin & Aging the study and the special challenges involved in treating heavy patients — particularly those who are obese.
Dr. Lebwohl, who is Professor and Chairman, Department of Dermatology at Mount Sinai School of Medicine, explained that the weight-based dosing in efalizumab offered these patients — whose lesions, like their bodies, are apt to be larger in size than those of lower-weight patients — a more appropriate amount of medication than one-size-fits-all options.
However, for patients who are obese — and psoriasis patients are twice as likely to be overweight compared to the general population — additional issues apply.
“This patient subpopulation may have lesions in skin folds that limit the use of topical agents and phototherapy, as well as comorbidities such as cardiovascular and metabolic diseases that restrict the use of some systemic agents,” he said.
Asked whether obesity in fact predisposes patients to psoriasis, Dr. Lebwohl said that the clearer connection was to disease severity and the vicious cycle of patients’ controlling their weight in the face of the discomfort and embarrassment of the often-disfiguring condition.
“Obesity is clearly associated with more severe psoriasis. To make matters worse, overweight patients with psoriasis are less likely to be physically active and may overeat as a result of low self esteem and other emotional issues,” he maintained. This, he added, exacerbates both the psoriasis and comorbidities associated with heavy individuals such as hypertension, diabetes, or high cholesterol which may influence a dermatologist’s choice of therapy for this subpopulation.
Study Method
Objective. The primary objective of this analysis was to investigate potential associations between PASI response and body weight. It additionally sought to analyze the association between dropout rates, adverse events, and serious adverse events with patient weight.
Patient selection. A total of 2,674 patients with PASI score ≥12 and a body surface area (BSA) of psoriasis ≥10% were included in these analyses. For the analysis of efficacy by patient weight, there were 1,318 patients <200 pounds, and 1,356 patients ≥200 pounds. For the analysis of safety by patient weight, 715 (26.7%) had received placebo, and 1,959 (73.3%) had received efalizumab. The analysis was conducted for three groups of patients from seven studies (four Phase III, and three open-label).
Analysis of PASI response. All data were analyzed in 12-week periods. The numbers and percentages of responders at the end of weeks 12 and 24 were summarized for each patient group by weight using intent-to-treat (ITT) analysis and dropouts were considered non-responders. For the long-term study, the numbers and percentages of responder were summarized at the end of each 3-month (12-week) period until 36 months by weight using ITT analysis where the last observation for dropouts was carried forward.
Findings
Efficacy. At 12 weeks, efficacy was similar for the two groups with 28% of non-heavy patients and 25% of patients achieving PASI-75. At 24 weeks, efficacy was similar for the two groups with 42% of non-heavy patients and 43% of heavy patients achieving PASI-75.
Adverse events. The incidence of adverse events and rate of infection was similar in both patient groups. The most common adverse events observed were a symptom complex that included headache, chills, fever, nausea, and myalgia within 48 hours following the first two injections.
Conclusion
Since efalizumab is dosed by weight, the authors observe, it may produce a more linear response profile across patients of all weights. However, based on the consistency of response and safety profile demonstrated in their study, they conclude that regardless of patient weight, efalizumab appears to be an appropriate biologic agent for heavier patients who have plaque psoriasis.
Lebwohl M, Compton P, Caro I. Efficacy and Safety of Treating Psoriatic Patients ≥200 Pounds with Efalizumab.
The Obesity-Psoriasis Connection
On behalf of the the International Psoriasis Council, a group of experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity.
Authors of the report published in the British Medical Journal noted that the strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care.
This meeting reviewed the evidence-based literature and addressed how in the future, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.
Overwhelmingly, the data presented at this meeting support the linkage of psoriasis to both obesity and increased comorbidity risk.
Recommendations
The authors ultimately offered these recommendations for future investigations:
1. Prospective analyses of broadly representative psoriatic populations with well-matched control populations should examine the chronology of psoriasis-associated obesity and the metabolic syndrome.
2. Psoriasis and obesity (or the metabolic syndrome) should be mechanistically, and not solely epidemiologically, demonstrated as inter-related and perhaps mutually potentiating. With that in mind, future investigations should examine not only the absolute levels of adipocytokines but also how the endocrine⁄immunological functions of adipose tissue directly interact with the pathophysiology of psoriasis.
3. The effects of various systemic therapies for psoriasis, including traditional and biological agents, on comorbidity need to be prospectively measured.
4. The effects of obesity on therapy should be evaluated.
5. This question should be addressed: Do direct interventions regarding weight loss, smoking and alcohol reduction and better lipid, glucose and blood pressure control positively affect psoriasis severity?
6. Future prospective psoriasis studies and registries, at a minimum, should capture weight and ⁄or abdominal circumference, height, comprehensive metabolic laboratory measurements, fasting lipids, and blood pressure measurements, so that potential relationships between cardiac risk factors and effective therapy can be established.
7. Biomarkers of psoriatic inflammation must be identified in patients.
8. Future studies should examine for the presence of psoriatic arthritis, which is now known to affect between 10% and 40% of patients with psoriasis. Furthermore, the findings of such studies should stratify the results based on the presence or absence of joint disease or, more specifically, enthesopathy.
9. Studies on circulating vascular endothelial progenitor cells should be evaluated in psoriasis populations.
10. Studies on the genetics of psoriasis should include examination of mutations in genes known to regulate adipose tissue, obesity, and other facets of the metabolic syndrome.
11. To accomplish the above objectives, the authors’ final recommendation is that dermatologists collaborate with colleagues in endocrinology, genetics, cardiology, vascular biology, hepatology, pharmacology and rheumatology to promote psoriasis as an important healthcare policy issue.
Conclusion
Pointing out its association with obesity and significant systemic inflammation and that it affects 2% of the population worldwide, the authors surmise that psoriasis warrants a more comprehensive, prospective and multidisciplinary investigative approach to better to clarify the nature of its comorbidities — both epidemiologically and mechanistically.
Sterry W, Strober BE, Menter A. Obesity In Psoriasis: The Metabolic, Clinical and Therapeutic Implications. Report of an Interdisciplinary Conference and Review. Br J Dermatol. 2007 Oct;157(4):649-55.
Ustekinumab Reduces Psoriasis Severity
Ustekinumab, an experimental self-injectable biologic that targets interleukins, was reportedly found to substantially reduced the severity of psoriasis.
According to the study of some 1,230 patients, more than two-thirds of those taking ustekinumab achieved at least a 75% reduction in psoriasis at week 12 of treatment versus 4% with placebo.
Many analysts consider ustekinumab a potential follow-up to Centocor’s existing anti-inflammatory
drug, Remicade.
Centocor filed a Biologics License Application for ustekinumab in early December 2007. Approval could come some time this year.
Psoriasis Patients Found to Generate Greater Health Care Costs Than Others
A retrospective analysis using the PharMetrics database of patients with a diagnosis of psoriasis (ICD-9 code 696.1) from January 1, 2000, through June 30, 2005, determined that this group generated healthcare costs and resource consumption at a much higher rate than non-psoriasis patients.
Methods
The study cohort consisted of 178,411 patients. Among them, 31,033 patients had psoriasis, more than 50% were females, and mean age was 43 years. Moderate to severe psoriasis patients had received treatment with biologics, systemic therapy, or phototherapy.
To be included in the analysis, patient had to have been continuously enrolled for 6 months pre- and 12 months post-psoriasis diagnosis and to have had two distinct claims for psoriasis. The control group of patients without an inflammatory disease diagnosis was matched on age and gender.
Mean per-patient healthcare costs and resource utilization were calculated for patients in the year following their initial psoriasis diagnosis. Multivariable linear regression analysis was conducted to determine the impact of psoriasis on total healthcare costs, adjusting for age, gender, and comorbidities (Deyo-Charlson comorbidity index score).
Results
Psoriasis patients had higher comorbidities than the controls (0.66 vs. 0.44, p<0.0001). Mean annual total healthcare costs for all psoriasis patients were $4,987, compared with $2,667 (p<0.0001) for controls. Inpatient and physician costs constituted over 50% of the total healthcare costs in the psoriasis cohort. Total healthcare visits were almost two times higher for the psoriasis cohort compared with the controls (15.3 vs. 7.5, p<0.0001). Physician office visits constituted 78% of the resource utilization in the psoriasis cohort.
In this study, 20.5% of the patients had moderate to severe psoriasis; moderate to severe psoriasis patients had three times higher mean total healthcare costs ($7,632 vs $2,376, p<0.0001) and mean total resource utilization (23.4 vs 6.7, p<0.0001) compared with controls.
After adjusting the regression analysis, psoriasis patients’ total healthcare costs were 175% higher than the controls. Patients with moderate to severe psoriasis had 251% higher costs compared with controls after adjusting the regression analysis.
Conclusions
Noting the high healthcare costs and resource consumption of psoriasis patients, the authors called for additional studies to assess differences in quality of life and health outcomes related to specific treatments for patients with psoriasis.
Dabbous O, Thompson HC, Meissner B, Rahman MI. Impact of Psoriasis on Healthcare Costs and Resource Utilization in Patients Compared to Patients Without Psoriasis from a Payer Perspective.
Infliximab Response Found to be Consistent Across Patients with Psoriasis
To assess the consistency of infliximab (Remicade) response among different subgroups of patients with moderate to severe psoriasis, the impact of gender, obesity, age, baseline psoriasis severity, concomitant psoriatic arthritis (PsA), or prior therapies on response to infliximab was studied in an integrated efficacy analysis.
Methods
Data from three randomized, placebo-controlled clinical trials (SPIRIT, EXPRESS and EXPRESS II) that evaluated the use of infliximab in patients with moderate to severe psoriasis were included in this integrated analysis.
Patients received placebo, infliximab 3 mg/kg, or infliximab 5 mg/kg at 0, 2 and 6 weeks. The common primary endpoint at week 10 was the proportion of patients achieving ≥75% improvement in the Psoriasis Area and Severity Index (PASI 75) from baseline. Safety data through week 16 were pooled for analysis.
Results
Of the 1,462 patients included in this analysis, 70.6% and 79.3% in the infliximab 3 and 5 mg/kg groups, respectively, achieved at least a PASI 75 response at week 10, compared with 2.7% in the placebo group (both p<0.001). The proportions of patients achieving PASI 75 at week 10 were consistent in subgroups defined by baseline demographic characteristics (gender, age, body mass index) and also defined by baseline disease characteristics (PASI severity, body surface area, presence of psoriatic arthritis). Consistent results were also observed regardless of psoriasis therapeutic history. Infliximab treatment was generally well tolerated by the majority of study participants.
Conclusion
A consistently high level of clinical response to infliximab was demonstrated across subgroups defined by a variety of baseline demographic and disease characteristics in patients with psoriasis. Infliximab was similarly effective regardless of previous use of phototherapy or major conventional systemic therapies.
The Obese Subgroup
Integrated efficacy analyses were conducted to determine the consistency of response to infliximab among different subgroups of patients — including those who were obese — with moderate to severe psoriasis within these three studies.
Responses by gender and baseline age (<40 years, ≥40 years) and by baseline body mass index (BMI; <25, ≥25 to <30, ≥3)were recorded and evaluated.
Reich K, Menter A, Plotnick M, Guzzo C, Li S, Gottlieb AB. Consistency of Infliximab Response Across Subgroups of Patients With Psoriasis: Integrated Results From Randomized Clinical Trials.
Phase III Data Suggest Golimumab (CNTO 148) Significantly Improves Skin and Nails As Well as Arthritis in Patients with Psoriatic Arthritis
According to findings from the largest Phase III biologic study ever completed in subjects with psoriatic arthritis, patients with active psoriatic arthritis receiving monthly subcutaneous injections of golimumab (CNTO 148), a next-generation human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, experienced significant and sustained improvements in the joint and skin manifestations of the disease, achieving primary and secondary endpoints
This 24-week efficacy and safety results of the randomized, placebo-controlled GO-REVEAL study showed that at week 14 of the 405-patient study in subjects with active psoriatic arthritis, 51% of patients receiving golimumab
50 mg and 45% of patients receiving golimumab 100 mg experienced at least 20% improvement in arthritis signs and symptoms (ACR 20) compared with 9% of patients receiving placebo (p < 0.001 for both comparisons). It further demonstrated that patients treated with golimumab, maintained significant improvements in arthritis through week 24. These patients also showed substantial and sustained improvements in skin and nail psoriatic disease (as measured by a 75% reduction in Psoriasis Area and Severity Index [PASI 75] in patients with baseline body surface area with psoriasis of at least 3%, and the Nail Psoriasis Severity Index [NAPSI]).
Key Data Points
Skin symptoms. At 14 weeks, 40% and 58% of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieved at least 75% improvement (PASI 75) in the skin symptoms of PsA. At 6 months, 56% and 66% of patients in the respective golimumab treatment groups achieved PASI 75.
Arthritis symptoms. At 14 weeks, 51% of patients receiving golimumab 50 mg and 45% of patients receiving golimumab 100 mg achieved at least a 20% reduction in signs and symptoms of PsA; 30% and 28% of patients in the respective golimumab treatment groups achieved at least a 50% reduction. These results persisted through 6 months.
The REVEAL Study
Objective. To assess the efficacy and safety of golimumab in reducing signs and symptoms of active PsA and associated skin and nail disease.
Patient Information. Enrolled population included 405 adults with at least three or more swollen and tender joints. Across placebo and golimumab groups at baseline, the mean age ranged from 46 to 48 years, the mean swollen/tender joint counts were 12-14/22-24, the mean HAQ scores were 1.0 to 1.1, and the mean PASI scores were 8.4 to 11.1. Placebo and golimumab groups were balanced for baseline demographic and disease characteristics.
Method
Patients were randomly assigned to receive subcutaneous injections of placebo (placebo) or golimumab (50 or 100 mg) at weeks 0, 4, 8, 12, 16, and 20.
Patients with inadequate arthritis response at week 16 were switched in a blinded manner to golimumab 50 mg (placebo patients) or golimumab 100 mg (golimumab 50 and 100 patients).
Placebo and golimumab 50 mg patients had their last observation prior to change in treatment carried forward for the week-24 efficacy analyses; the observed values at week 24 were used for golimumab 100 patients.
Concomitant methotrexate was allowed but not required.
The primary endpoint (ACR20 at week 14) was analyzed by the Cochran-Mantel-Haenszel test with stratification by methotrexate use.
Results
Efficacy. Golimumab was found to be significantly better than placebo in improving signs and symptoms of PsA .
The two golimumab doses were comparable in efficacy, and patients switching from golimumab 50 to 100 had minimal improvement from week 16 to 24.
Concomitant methotrexate did not affect efficacy.
Safety. Golimumab was generally well tolerated, with 2.4% of golimumab patients experiencing serious adverse events (SAEs) through week 24 vs. 6.2% of placebo patients. Injection site reactions were rare and occurred in 4.8% of golimumab and 2.7% of placebo patients. Antibodies to golimumab were detected in 4.6% of golimumab patients through week 24. One SAE of malignancy (prostate cancer) and two cases of basal cell carcinoma were reported in golimumab patients. There were no reports of tuberculosis or opportunistic infections.
Conclusion
In patients with active PsA, golimumab 50 and 100 mg for 24 weeks significantly improved active PsA and psoriatic skin and nail disease through week 24 and was generally well tolerated.
Abbott’s ABT-874 Found Highly Effective For Psoriasis Even After Discontinuation
A Phase II study evaluating the effectiveness of Abbott’s investigational anti-IL-12/23 antibody ABT-874 showed that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy. In the study, patients who achieved 75% improvement in psoriasis signs and symptoms (PASI 75) at 12 weeks stopped receiving ABT-874. At 24 weeks, more than two-thirds of these patients maintained at least 50% improvement (PASI 50).
Study Background and Results
Initial Phase II Study
In a 12-week, double-blind, placebo-controlled study, 180 patients with moderate to severe psoriasis were randomized evenly to six treatment groups: a single, subcutaneous 200-mg injection of ABT-874 at week zero; 100 mg every other week for 12 weeks; 200 mg weekly for 4 weeks; 200 mg every other week for 12 weeks; 200 mg weekly for 12 weeks; or matching placebo. The primary study endpoint was the proportion of patients achieving 75% improvement in the degree and severity of skin lesions after 12 weeks, measured by the Psoriasis Area and Severity Index (PASI).
At least 90% of patients achieved PASI 75 at week 12 in all ABT-874 treatment groups except the single-dose group (200 mg at week zero). (Results were, respectively, 63%, 93%, 90%, 93%, and 90%, vs. 3% of those receiving placebo; p<0.001 for all groups.) Also, in the same four treatment groups, more than half of patients achieved 90% improvement in skin clearance (results were, respectively, 17%, 53%, 63%, 77%, 53%, vs. 0% of those receiving placebo; p<0.001 for all groups except the single-dose group, 200 mg at week 0).
Continuation Study
A Phase II follow-up study evaluating the effectiveness of ABT-874 in patients with moderate to severe psoriasis found that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy.
In the continuation of the Phase II study, treatment with ABT-874 was discontinued in patients who met the primary endpoint. Maintenance of PASI response was evaluated through week 48.
Reported results from 24 weeks. Substantial percentages of PASI 75 responders in the active treatments arms had maintained ≥ PASI 50 responses. Results were 68% (13 out of 19 patients), 71% (20 of 28), 81% (22 of 27), 89% (25 of 28), and 85% (23 of 27) in the five ABT-874 dosing groups, respectively.
Adverse events. The most common adverse events observed were injection-site reactions, nasopharyngitis, upper respiratory infections, and response that is not addressed by any therapy available today.
