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Earlier Is Better in Psoriasis Treatment
RIO GRANDE, P.R. – Treating psoriasis patients earlier in life could help prevent later physical and psychological problems, according to Dr. Alexa B. Kimball.
"We used to think that we should save our therapies until our patients really needed them, because we were afraid that toxicity might accumulate," Dr. Kimball said at the annual Caribbean Dermatology Symposium. However, that thinking has changed, thanks in part to the availability of safer treatment options.
But of equal importance, "treating patients early in their disease may have an impact that affects the rest of their lives," including jobs, education, socioeconomic status, and curbing the development of health problems like obesity, cardiovascular disease, and psychiatric disorders, she said.
The quality of life issues associated with psoriasis are well known, but recent data confirm that physical and mental comorbidities start in childhood.
According to recent data from the National Psoriasis Foundation, 38% of children with psoriasis reported being bullied because of their condition, noted Dr. Kimball of Massachusetts General Hospital and Harvard Medical School, both in Boston.
Another study found that approximately one-third of children aged 4-17 years with psoriasis had a body mass index greater than the 95th percentile (N. Engl. J. Med. 2008;358:241-51). Conditions such as childhood obesity are not easily managed, and have significant implications for future health, she said.
In a retrospective study of 7,404 psoriasis patients younger than 18 years and 37,020 healthy controls, children with psoriasis were significantly more likely than controls to develop any psychiatric disorder (5% vs. 4%), depression (3% vs. 2%), and anxiety (2% vs. 1%), Dr. Kimball and her colleagues found (J. Am. Acad. Dermatol. 2012 Jan. 16 [doi:10.1016/j.jaad.2011.11.948]).
And the likelihood of comorbidities in psoriasis patients continues as they grow up, she said. "Chronic disease interacts with psychosocial and health events in a complex and ongoing manner throughout a person’s life."
Comorbidities in psoriasis patients appear to accumulate over time. Dr. Kimball cited data from the Nurses’ Health Study II, a cohort including more than 100,000 women who were aged 27-44 years in 1991. In a subset of 1,813 women with psoriasis, the risk of diabetes was approximately 60% higher, and the risk of hypertension was almost 20% higher, compared with women without psoriasis (Arch. Dermatol. 2009;145:379-82).
In a case-control study conducted by Dr. Kimball and her colleagues, cardiovascular disease, diabetes, depression, hyperlipidemia, hypertension, and obesity all increased significantly in psoriasis patients, compared with healthy controls, over a 4-year follow-up period (J. Am. Acad. Dermatol. 2010;62[suppl. 1]:AB3).
These findings suggest that medical comorbidities associated with psoriasis accumulate over time; therefore, aggressive treatment of psoriasis in younger patients could improve their psychological and physical quality of life, Dr. Kimball said. Although there are no recommendations for additional health screening for psoriasis patients beyond the age-recommended preventive health measures, "younger patients especially need to be monitored for psychiatric issues," she said. And these patients should be kept up to date on vaccinations, particularly the annual flu vaccine and the human papillomavirus vaccine.
Dr. Kimball reported receiving grants, honoraria, consulting fees, and other support from Abbott, Amgen, and Janssen Pharmaceuticals.
RIO GRANDE, P.R. – Treating psoriasis patients earlier in life could help prevent later physical and psychological problems, according to Dr. Alexa B. Kimball.
"We used to think that we should save our therapies until our patients really needed them, because we were afraid that toxicity might accumulate," Dr. Kimball said at the annual Caribbean Dermatology Symposium. However, that thinking has changed, thanks in part to the availability of safer treatment options.
But of equal importance, "treating patients early in their disease may have an impact that affects the rest of their lives," including jobs, education, socioeconomic status, and curbing the development of health problems like obesity, cardiovascular disease, and psychiatric disorders, she said.
The quality of life issues associated with psoriasis are well known, but recent data confirm that physical and mental comorbidities start in childhood.
According to recent data from the National Psoriasis Foundation, 38% of children with psoriasis reported being bullied because of their condition, noted Dr. Kimball of Massachusetts General Hospital and Harvard Medical School, both in Boston.
Another study found that approximately one-third of children aged 4-17 years with psoriasis had a body mass index greater than the 95th percentile (N. Engl. J. Med. 2008;358:241-51). Conditions such as childhood obesity are not easily managed, and have significant implications for future health, she said.
In a retrospective study of 7,404 psoriasis patients younger than 18 years and 37,020 healthy controls, children with psoriasis were significantly more likely than controls to develop any psychiatric disorder (5% vs. 4%), depression (3% vs. 2%), and anxiety (2% vs. 1%), Dr. Kimball and her colleagues found (J. Am. Acad. Dermatol. 2012 Jan. 16 [doi:10.1016/j.jaad.2011.11.948]).
And the likelihood of comorbidities in psoriasis patients continues as they grow up, she said. "Chronic disease interacts with psychosocial and health events in a complex and ongoing manner throughout a person’s life."
Comorbidities in psoriasis patients appear to accumulate over time. Dr. Kimball cited data from the Nurses’ Health Study II, a cohort including more than 100,000 women who were aged 27-44 years in 1991. In a subset of 1,813 women with psoriasis, the risk of diabetes was approximately 60% higher, and the risk of hypertension was almost 20% higher, compared with women without psoriasis (Arch. Dermatol. 2009;145:379-82).
In a case-control study conducted by Dr. Kimball and her colleagues, cardiovascular disease, diabetes, depression, hyperlipidemia, hypertension, and obesity all increased significantly in psoriasis patients, compared with healthy controls, over a 4-year follow-up period (J. Am. Acad. Dermatol. 2010;62[suppl. 1]:AB3).
These findings suggest that medical comorbidities associated with psoriasis accumulate over time; therefore, aggressive treatment of psoriasis in younger patients could improve their psychological and physical quality of life, Dr. Kimball said. Although there are no recommendations for additional health screening for psoriasis patients beyond the age-recommended preventive health measures, "younger patients especially need to be monitored for psychiatric issues," she said. And these patients should be kept up to date on vaccinations, particularly the annual flu vaccine and the human papillomavirus vaccine.
Dr. Kimball reported receiving grants, honoraria, consulting fees, and other support from Abbott, Amgen, and Janssen Pharmaceuticals.
RIO GRANDE, P.R. – Treating psoriasis patients earlier in life could help prevent later physical and psychological problems, according to Dr. Alexa B. Kimball.
"We used to think that we should save our therapies until our patients really needed them, because we were afraid that toxicity might accumulate," Dr. Kimball said at the annual Caribbean Dermatology Symposium. However, that thinking has changed, thanks in part to the availability of safer treatment options.
But of equal importance, "treating patients early in their disease may have an impact that affects the rest of their lives," including jobs, education, socioeconomic status, and curbing the development of health problems like obesity, cardiovascular disease, and psychiatric disorders, she said.
The quality of life issues associated with psoriasis are well known, but recent data confirm that physical and mental comorbidities start in childhood.
According to recent data from the National Psoriasis Foundation, 38% of children with psoriasis reported being bullied because of their condition, noted Dr. Kimball of Massachusetts General Hospital and Harvard Medical School, both in Boston.
Another study found that approximately one-third of children aged 4-17 years with psoriasis had a body mass index greater than the 95th percentile (N. Engl. J. Med. 2008;358:241-51). Conditions such as childhood obesity are not easily managed, and have significant implications for future health, she said.
In a retrospective study of 7,404 psoriasis patients younger than 18 years and 37,020 healthy controls, children with psoriasis were significantly more likely than controls to develop any psychiatric disorder (5% vs. 4%), depression (3% vs. 2%), and anxiety (2% vs. 1%), Dr. Kimball and her colleagues found (J. Am. Acad. Dermatol. 2012 Jan. 16 [doi:10.1016/j.jaad.2011.11.948]).
And the likelihood of comorbidities in psoriasis patients continues as they grow up, she said. "Chronic disease interacts with psychosocial and health events in a complex and ongoing manner throughout a person’s life."
Comorbidities in psoriasis patients appear to accumulate over time. Dr. Kimball cited data from the Nurses’ Health Study II, a cohort including more than 100,000 women who were aged 27-44 years in 1991. In a subset of 1,813 women with psoriasis, the risk of diabetes was approximately 60% higher, and the risk of hypertension was almost 20% higher, compared with women without psoriasis (Arch. Dermatol. 2009;145:379-82).
In a case-control study conducted by Dr. Kimball and her colleagues, cardiovascular disease, diabetes, depression, hyperlipidemia, hypertension, and obesity all increased significantly in psoriasis patients, compared with healthy controls, over a 4-year follow-up period (J. Am. Acad. Dermatol. 2010;62[suppl. 1]:AB3).
These findings suggest that medical comorbidities associated with psoriasis accumulate over time; therefore, aggressive treatment of psoriasis in younger patients could improve their psychological and physical quality of life, Dr. Kimball said. Although there are no recommendations for additional health screening for psoriasis patients beyond the age-recommended preventive health measures, "younger patients especially need to be monitored for psychiatric issues," she said. And these patients should be kept up to date on vaccinations, particularly the annual flu vaccine and the human papillomavirus vaccine.
Dr. Kimball reported receiving grants, honoraria, consulting fees, and other support from Abbott, Amgen, and Janssen Pharmaceuticals.
EXPERT ANALYSIS FROM THE ANNUAL CARIBBEAN DERMATOLOGY SYMPOSIUM
Malignancy Rates Remain Stable in Ustekinumab-Treated Patients
RIO GRANDE, P.R. – Malignancy rates in psoriasis patients treated with ustekinumab did not increase significantly over 4 years of follow-up, based on pooled data from 3,117 patients enrolled in ustekinumab clinical trials.
Ustekinumab has shown effectiveness for treating moderate to severe psoriasis, but due to the potential of increased risk for cancer associated with its use, patients from several clinical trials (including PHOENIX I, PHOENIX II, and ACCEPT) are still being followed, said Dr. Kim A. Papp, director of research at Probity Medical Research, Waterloo, Ont., and colleagues.
The cumulative rates for nonmelanoma skin cancer in patients treated with ustekinumab for psoriasis remained low and stable throughout the follow-up period. A total of 0.57 cancer events per 100 person-years were reported in 2009 and 0.62 cancer events per 100 person-years were reported in 2010. The findings were presented at the annual Caribbean Dermatology Symposium.
In the complete analysis that included 6,791 patient-years of follow-up, 41 patients treated with any dose of ustekinumab developed at least one nonmelanoma skin cancer, and 3 patients developed both basal cell carcinoma and squamous cell carcinoma.
Another 42 patients developed at least one other malignancy, including 4 patients with melanoma in situ. However, no cases of invasive melanoma were observed during the study period. The other most common malignancies were prostate cancer (12 patients), colorectal cancer (4 patients) and breast cancer (3 patients).
By comparison, 39 individuals in the general population (based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results database) developed at least one malignancy.
The findings were limited by the inclusion of several studies of varying lengths and by the inclusion criteria that can make comparison with the general population difficult, the researchers noted. The results suggest that rates of nonmelanoma skin cancer and other malignancies in psoriasis patients taking ustekinumab do not increase over time.
However, "additional long term data from clinical trials, observational registries, and postmarketing reporting databases will continue to define the ustekinumab malignancy risk profile," they wrote.
The study was sponsored by Centocor, which manufactures ustekinmab.
RIO GRANDE, P.R. – Malignancy rates in psoriasis patients treated with ustekinumab did not increase significantly over 4 years of follow-up, based on pooled data from 3,117 patients enrolled in ustekinumab clinical trials.
Ustekinumab has shown effectiveness for treating moderate to severe psoriasis, but due to the potential of increased risk for cancer associated with its use, patients from several clinical trials (including PHOENIX I, PHOENIX II, and ACCEPT) are still being followed, said Dr. Kim A. Papp, director of research at Probity Medical Research, Waterloo, Ont., and colleagues.
The cumulative rates for nonmelanoma skin cancer in patients treated with ustekinumab for psoriasis remained low and stable throughout the follow-up period. A total of 0.57 cancer events per 100 person-years were reported in 2009 and 0.62 cancer events per 100 person-years were reported in 2010. The findings were presented at the annual Caribbean Dermatology Symposium.
In the complete analysis that included 6,791 patient-years of follow-up, 41 patients treated with any dose of ustekinumab developed at least one nonmelanoma skin cancer, and 3 patients developed both basal cell carcinoma and squamous cell carcinoma.
Another 42 patients developed at least one other malignancy, including 4 patients with melanoma in situ. However, no cases of invasive melanoma were observed during the study period. The other most common malignancies were prostate cancer (12 patients), colorectal cancer (4 patients) and breast cancer (3 patients).
By comparison, 39 individuals in the general population (based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results database) developed at least one malignancy.
The findings were limited by the inclusion of several studies of varying lengths and by the inclusion criteria that can make comparison with the general population difficult, the researchers noted. The results suggest that rates of nonmelanoma skin cancer and other malignancies in psoriasis patients taking ustekinumab do not increase over time.
However, "additional long term data from clinical trials, observational registries, and postmarketing reporting databases will continue to define the ustekinumab malignancy risk profile," they wrote.
The study was sponsored by Centocor, which manufactures ustekinmab.
RIO GRANDE, P.R. – Malignancy rates in psoriasis patients treated with ustekinumab did not increase significantly over 4 years of follow-up, based on pooled data from 3,117 patients enrolled in ustekinumab clinical trials.
Ustekinumab has shown effectiveness for treating moderate to severe psoriasis, but due to the potential of increased risk for cancer associated with its use, patients from several clinical trials (including PHOENIX I, PHOENIX II, and ACCEPT) are still being followed, said Dr. Kim A. Papp, director of research at Probity Medical Research, Waterloo, Ont., and colleagues.
The cumulative rates for nonmelanoma skin cancer in patients treated with ustekinumab for psoriasis remained low and stable throughout the follow-up period. A total of 0.57 cancer events per 100 person-years were reported in 2009 and 0.62 cancer events per 100 person-years were reported in 2010. The findings were presented at the annual Caribbean Dermatology Symposium.
In the complete analysis that included 6,791 patient-years of follow-up, 41 patients treated with any dose of ustekinumab developed at least one nonmelanoma skin cancer, and 3 patients developed both basal cell carcinoma and squamous cell carcinoma.
Another 42 patients developed at least one other malignancy, including 4 patients with melanoma in situ. However, no cases of invasive melanoma were observed during the study period. The other most common malignancies were prostate cancer (12 patients), colorectal cancer (4 patients) and breast cancer (3 patients).
By comparison, 39 individuals in the general population (based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results database) developed at least one malignancy.
The findings were limited by the inclusion of several studies of varying lengths and by the inclusion criteria that can make comparison with the general population difficult, the researchers noted. The results suggest that rates of nonmelanoma skin cancer and other malignancies in psoriasis patients taking ustekinumab do not increase over time.
However, "additional long term data from clinical trials, observational registries, and postmarketing reporting databases will continue to define the ustekinumab malignancy risk profile," they wrote.
The study was sponsored by Centocor, which manufactures ustekinmab.
FROM THE ANNUAL CARIBBEAN DERMATOLOGY SYMPOSIUM
Major Finding: A total of 0.57 cancer events per 100 person-years were reported in 2009 and 0.62 cancer events per 100 person-years were reported in 2010.
Data Source: A review of 3,117 adults with psoriasis who were enrolled in ustekinumab clinical trials.
Disclosures: The study was sponsored by Centocor, which manufactures ustekinumab.
Infliximab Switch Clears Psoriasis in Etanercept Nonresponders
Switching to infliximab after an inadequate response to etanercept was associated with a Physician Global Assessment score of clear or minimal in nearly two-thirds of patients with plaque psoriasis, based on results of a multicenter, open-label study.
This approach "offers an alternative therapeutic paradigm for patients with psoriasis who do not respond to initial treatment with a TNF [tumor necrosis factor]-alpha antagonist or those who lose response during anti-TNF-alpha treatment," the researchers wrote in a report that appeared online Dec. 8, 2011, in the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2011.10.020). "Additional studies are necessary to fully define the risks and benefits of transitions of this type for the treatment of psoriasis."
In an interview, lead study author Dr. Alice B. Gottlieb, professor and chair of dermatology at Tufts Medical Center, Boston, characterized the findings as important, "because many practitioners assume that if a patient does not respond to one TNF-alpha blocker – or if they have lost response to one TNF-alpha blocker – that another TNF-alpha blocker will not work. That’s just not true."
For the open-label study, known as PSUNRISE, Dr. Gottlieb and her associates at 49 centers in North America enrolled 215 adults with moderate to severe plaque psoriasis and an inadequate response to at least 4 months of treatment with etanercept (Enbrel). They were eligible for the trial if they had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Treatment consisted of intravenous infusions of infliximab (Remicade) 5 mg/kg at baseline and weeks 2, 6, 14, and 22.
The study’s primary end point was the proportion of patients who achieved a PGA score of clear (0) or minimal (1) at week 10. Secondary end points included the proportion of patients who achieved a PGA score of 0 or 1 at week 26. Adverse events were documented through week 30.
Of the 215 patients, 36 withdrew consent or terminated their participation, one of whom returned at week 30. This left 179 patients who completed the study and 180 who completed the 30-week follow-up. The mean age of patients was 44 years, 64% were male, and 90% were white.
By week 10, 65% of patients achieved a PGA of 0 or 1, a score that was maintained in 61% of patients at week 26. Overall, 54% of patients had at least two grades of improvement in their PGA score.
In addition, mean Psoriasis Area and Severity Index scores decreased from 11.6 at baseline to 2.8 at week 10 and week 26, while Dermatology Life Quality Index scores of 0 or 1 were achieved by 44% of patients at week 10 and 41% of patients at week 26.
No unexpected side effects or safety concerns were reported. Eight patients (4%) had a serious adverse event; no cases of tuberculosis were observed. "Overall, the type and incidence of adverse events observed after switching from etanercept to infliximab in this study were similar to those reported in large, controlled trials of infliximab in patients with moderate to severe psoriasis," the researchers wrote.
They acknowledged certain limitations of their study, including data bias "and uncontrolled systematic errors, that are not present in a blinded, controlled randomized study. In addition, it would be easier to interpret the study results if a comparator group were included in the study design."
Dr. Gottlieb, who reported the first double-blind, placebo-controlled study of infliximab monotherapy in psoriasis (Lancet 2001;357:1842-7), encouraged more dermatologists to add infliximab to their drug repertoire for severe psoriasis, "because it works in a high percentage of patients, it works quickly, and it can work when other TNF-alpha blockers don’t."
The study was supported by Janssen Biotech, which manufactures Remicade and is a subsidiary of Johnson & Johnson. Dr. Gottlieb disclosed that she has current consulting/advisory board agreements with several pharmaceutical companies, including Amgen and Pfizer, which market Enbrel, but not with Janssen Biotech. Two of the study authors, Dr. Marc Chevrier and Stephen Calabro, are employees of Janssen Biotech.
Switching to infliximab after an inadequate response to etanercept was associated with a Physician Global Assessment score of clear or minimal in nearly two-thirds of patients with plaque psoriasis, based on results of a multicenter, open-label study.
This approach "offers an alternative therapeutic paradigm for patients with psoriasis who do not respond to initial treatment with a TNF [tumor necrosis factor]-alpha antagonist or those who lose response during anti-TNF-alpha treatment," the researchers wrote in a report that appeared online Dec. 8, 2011, in the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2011.10.020). "Additional studies are necessary to fully define the risks and benefits of transitions of this type for the treatment of psoriasis."
In an interview, lead study author Dr. Alice B. Gottlieb, professor and chair of dermatology at Tufts Medical Center, Boston, characterized the findings as important, "because many practitioners assume that if a patient does not respond to one TNF-alpha blocker – or if they have lost response to one TNF-alpha blocker – that another TNF-alpha blocker will not work. That’s just not true."
For the open-label study, known as PSUNRISE, Dr. Gottlieb and her associates at 49 centers in North America enrolled 215 adults with moderate to severe plaque psoriasis and an inadequate response to at least 4 months of treatment with etanercept (Enbrel). They were eligible for the trial if they had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Treatment consisted of intravenous infusions of infliximab (Remicade) 5 mg/kg at baseline and weeks 2, 6, 14, and 22.
The study’s primary end point was the proportion of patients who achieved a PGA score of clear (0) or minimal (1) at week 10. Secondary end points included the proportion of patients who achieved a PGA score of 0 or 1 at week 26. Adverse events were documented through week 30.
Of the 215 patients, 36 withdrew consent or terminated their participation, one of whom returned at week 30. This left 179 patients who completed the study and 180 who completed the 30-week follow-up. The mean age of patients was 44 years, 64% were male, and 90% were white.
By week 10, 65% of patients achieved a PGA of 0 or 1, a score that was maintained in 61% of patients at week 26. Overall, 54% of patients had at least two grades of improvement in their PGA score.
In addition, mean Psoriasis Area and Severity Index scores decreased from 11.6 at baseline to 2.8 at week 10 and week 26, while Dermatology Life Quality Index scores of 0 or 1 were achieved by 44% of patients at week 10 and 41% of patients at week 26.
No unexpected side effects or safety concerns were reported. Eight patients (4%) had a serious adverse event; no cases of tuberculosis were observed. "Overall, the type and incidence of adverse events observed after switching from etanercept to infliximab in this study were similar to those reported in large, controlled trials of infliximab in patients with moderate to severe psoriasis," the researchers wrote.
They acknowledged certain limitations of their study, including data bias "and uncontrolled systematic errors, that are not present in a blinded, controlled randomized study. In addition, it would be easier to interpret the study results if a comparator group were included in the study design."
Dr. Gottlieb, who reported the first double-blind, placebo-controlled study of infliximab monotherapy in psoriasis (Lancet 2001;357:1842-7), encouraged more dermatologists to add infliximab to their drug repertoire for severe psoriasis, "because it works in a high percentage of patients, it works quickly, and it can work when other TNF-alpha blockers don’t."
The study was supported by Janssen Biotech, which manufactures Remicade and is a subsidiary of Johnson & Johnson. Dr. Gottlieb disclosed that she has current consulting/advisory board agreements with several pharmaceutical companies, including Amgen and Pfizer, which market Enbrel, but not with Janssen Biotech. Two of the study authors, Dr. Marc Chevrier and Stephen Calabro, are employees of Janssen Biotech.
Switching to infliximab after an inadequate response to etanercept was associated with a Physician Global Assessment score of clear or minimal in nearly two-thirds of patients with plaque psoriasis, based on results of a multicenter, open-label study.
This approach "offers an alternative therapeutic paradigm for patients with psoriasis who do not respond to initial treatment with a TNF [tumor necrosis factor]-alpha antagonist or those who lose response during anti-TNF-alpha treatment," the researchers wrote in a report that appeared online Dec. 8, 2011, in the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2011.10.020). "Additional studies are necessary to fully define the risks and benefits of transitions of this type for the treatment of psoriasis."
In an interview, lead study author Dr. Alice B. Gottlieb, professor and chair of dermatology at Tufts Medical Center, Boston, characterized the findings as important, "because many practitioners assume that if a patient does not respond to one TNF-alpha blocker – or if they have lost response to one TNF-alpha blocker – that another TNF-alpha blocker will not work. That’s just not true."
For the open-label study, known as PSUNRISE, Dr. Gottlieb and her associates at 49 centers in North America enrolled 215 adults with moderate to severe plaque psoriasis and an inadequate response to at least 4 months of treatment with etanercept (Enbrel). They were eligible for the trial if they had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Treatment consisted of intravenous infusions of infliximab (Remicade) 5 mg/kg at baseline and weeks 2, 6, 14, and 22.
The study’s primary end point was the proportion of patients who achieved a PGA score of clear (0) or minimal (1) at week 10. Secondary end points included the proportion of patients who achieved a PGA score of 0 or 1 at week 26. Adverse events were documented through week 30.
Of the 215 patients, 36 withdrew consent or terminated their participation, one of whom returned at week 30. This left 179 patients who completed the study and 180 who completed the 30-week follow-up. The mean age of patients was 44 years, 64% were male, and 90% were white.
By week 10, 65% of patients achieved a PGA of 0 or 1, a score that was maintained in 61% of patients at week 26. Overall, 54% of patients had at least two grades of improvement in their PGA score.
In addition, mean Psoriasis Area and Severity Index scores decreased from 11.6 at baseline to 2.8 at week 10 and week 26, while Dermatology Life Quality Index scores of 0 or 1 were achieved by 44% of patients at week 10 and 41% of patients at week 26.
No unexpected side effects or safety concerns were reported. Eight patients (4%) had a serious adverse event; no cases of tuberculosis were observed. "Overall, the type and incidence of adverse events observed after switching from etanercept to infliximab in this study were similar to those reported in large, controlled trials of infliximab in patients with moderate to severe psoriasis," the researchers wrote.
They acknowledged certain limitations of their study, including data bias "and uncontrolled systematic errors, that are not present in a blinded, controlled randomized study. In addition, it would be easier to interpret the study results if a comparator group were included in the study design."
Dr. Gottlieb, who reported the first double-blind, placebo-controlled study of infliximab monotherapy in psoriasis (Lancet 2001;357:1842-7), encouraged more dermatologists to add infliximab to their drug repertoire for severe psoriasis, "because it works in a high percentage of patients, it works quickly, and it can work when other TNF-alpha blockers don’t."
The study was supported by Janssen Biotech, which manufactures Remicade and is a subsidiary of Johnson & Johnson. Dr. Gottlieb disclosed that she has current consulting/advisory board agreements with several pharmaceutical companies, including Amgen and Pfizer, which market Enbrel, but not with Janssen Biotech. Two of the study authors, Dr. Marc Chevrier and Stephen Calabro, are employees of Janssen Biotech.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Major Finding: After switching to infliximab, 65% of patients with plaque psoriasis had a Physician Global Assessment score of clear (0) or minimal (1) at week 10. This response was durable through week 26.
Data Source: An open-label, multicenter study of 215 patients with plaque psoriasis who had an inadequate response to etanercept and who received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22.
Disclosures: Dr. Gottlieb disclosed that she has current consulting/advisory board agreements with several pharmaceutical companies, including Amgen and Pfizer, but not with Janssen Biotech. Two of the study authors, Dr. Marc Chevrier and Stephen Calabro, are employees of Janssen Biotech.
Ondansetron Quells Methotrexate-Induced Nausea
LISBON – Getting an earful of complaints of nausea from your patients on oral methotrexate therapy?
Consider bracketing the antifolate drug with the antiemetic ondansetron before and afterward, Dr. Richard B. Warren suggested at the congress.
"One successful means of helping patients overcome their nausea that we’ve used a lot in Manchester is ondansetron. For some people it can literally sort out the nausea altogether," said Dr. Warren, senior lecturer and honorary consultant dermatologist at the University of Manchester (England).
The dosing is 8 mg of ondansetron (Zofran) – a serotonin receptor antagonist used to treat nausea caused by chemotherapy, radiation therapy, and/or surgery – administered 2 hours before and once again 12 hours after taking methotrexate.
Nausea is a common nuisance side effect of the drug. It affects roughly one-quarter of patients, typically beginning about 12 hours after they take their weekly dose. The nausea can last for up to 72 hours.
In addition to prophylactic ondansetron, other strategies that may be effective in overcoming methotrexate-induced nausea include the following:
– Divide the dose.
– Have patients take their oral methotrexate with the evening meal.
– Consider switching to subcutaneous methotrexate. "It has been shown to be more efficacious, and with less in the way of adverse events than oral methotrexate," Dr. Warren said.
He declared having no relevant financial interests.
LISBON – Getting an earful of complaints of nausea from your patients on oral methotrexate therapy?
Consider bracketing the antifolate drug with the antiemetic ondansetron before and afterward, Dr. Richard B. Warren suggested at the congress.
"One successful means of helping patients overcome their nausea that we’ve used a lot in Manchester is ondansetron. For some people it can literally sort out the nausea altogether," said Dr. Warren, senior lecturer and honorary consultant dermatologist at the University of Manchester (England).
The dosing is 8 mg of ondansetron (Zofran) – a serotonin receptor antagonist used to treat nausea caused by chemotherapy, radiation therapy, and/or surgery – administered 2 hours before and once again 12 hours after taking methotrexate.
Nausea is a common nuisance side effect of the drug. It affects roughly one-quarter of patients, typically beginning about 12 hours after they take their weekly dose. The nausea can last for up to 72 hours.
In addition to prophylactic ondansetron, other strategies that may be effective in overcoming methotrexate-induced nausea include the following:
– Divide the dose.
– Have patients take their oral methotrexate with the evening meal.
– Consider switching to subcutaneous methotrexate. "It has been shown to be more efficacious, and with less in the way of adverse events than oral methotrexate," Dr. Warren said.
He declared having no relevant financial interests.
LISBON – Getting an earful of complaints of nausea from your patients on oral methotrexate therapy?
Consider bracketing the antifolate drug with the antiemetic ondansetron before and afterward, Dr. Richard B. Warren suggested at the congress.
"One successful means of helping patients overcome their nausea that we’ve used a lot in Manchester is ondansetron. For some people it can literally sort out the nausea altogether," said Dr. Warren, senior lecturer and honorary consultant dermatologist at the University of Manchester (England).
The dosing is 8 mg of ondansetron (Zofran) – a serotonin receptor antagonist used to treat nausea caused by chemotherapy, radiation therapy, and/or surgery – administered 2 hours before and once again 12 hours after taking methotrexate.
Nausea is a common nuisance side effect of the drug. It affects roughly one-quarter of patients, typically beginning about 12 hours after they take their weekly dose. The nausea can last for up to 72 hours.
In addition to prophylactic ondansetron, other strategies that may be effective in overcoming methotrexate-induced nausea include the following:
– Divide the dose.
– Have patients take their oral methotrexate with the evening meal.
– Consider switching to subcutaneous methotrexate. "It has been shown to be more efficacious, and with less in the way of adverse events than oral methotrexate," Dr. Warren said.
He declared having no relevant financial interests.
EXPERT OPINION FROM THE ANNUAL CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Preterm Delivery a Risk in Systemic Sclerosis
Many women with systemic sclerosis can have successful pregnancies, but the rates of preterm birth, low birth weight, and intrauterine growth restriction are approximately twice as high in these women compared to the general population of pregnant women, based on data from 109 pregnancies in 99 women with systemic sclerosis.
The findings were published in Arthritis & Rheumatism (Arthritis Rheum. 2011 Dec. 28 [doi:10.1002/art.34350]).
Data from previous studies have suggested negative outcomes for pregnancies in women with systemic sclerosis (SSc), but these have been small case series or large database reviews that did not allow for the identification of individual patients, said Dr. Mara Taraborelli of Spedali Civili and University, Brescia, Italy, and colleagues.
In this prospective study, the researchers followed 99 women with SSc who had 109 pregnancies between 2000 and 2011. The women attended one of 25 participating research centers in Italy.
The average age at conception was 32 years, and most of the women were white. A total of 107 pregnancies were spontaneous, and 2 were achieved with assisted reproductive techniques.
Preterm deliveries were significantly more common in the SSc women, compared to the general obstetric population that served as a control group (25% vs. 12%, respectively). Severe preterm delivery (defined as delivery at less than 34 weeks) also was significantly more common in SSc women, compared to the controls (10% vs. 5%, respectively).
In addition, very low birth weight babies and cases of intrauterine growth restriction were significantly more common in the SSc women, compared to the controls (5% vs. 1%, respectively, and 6% vs. 1%, respectively).
The researchers found no increase in hypertensive disorders of pregnancy or spontaneous pregnancy losses in SSc women, compared to the general pregnant population.
"We observed a low rate of disease progression shortly after the end of pregnancy; this risk might be greater in aSCL-70 positive patients with recent-onset disease," the researchers noted. All four cases of internal organ disease evolution within 12 months after delivery occurred in women who were aSCL-70 positive, and 3 of 23 (13%) of women who were aSCL-70 positive whose disease had lasted less than 3 years had some disease progression after delivery.
A total of six newborns spent a median of 15 days in the intensive care unit. Of these, one was severely premature and died of multi-organ failure.
The study findings were limited by the use of retrospective analysis and the use of controls for only one year, but the results suggest that successful pregnancies are possible for SSc women despite the increased risks for poor maternal and fetal outcomes, with multidisciplinary management, the researchers said. However, pregnancy may not be advisable for patients with severe organ damage or recent onset of SSc, especially those who are antitopoisomerase positive, they added.
The researchers had no financial conflicts to disclose. The study was supported in part by three patients’ associations: the Gruppo Italiano Lotta alla Sclerodermia, Gruppo Lupus Eritematoso Sistemico Lombardia, and the Associazone Lombarda Malati Reumatici.
Findings from this study and other studies on pregnancy in women with systemic sclerosis are important because many affected patients are in their child-bearing years.
This is one of several studies on the topic of SSc and pregnancy, and findings from the other studies do not agree fully with these data. Findings from other studies have shown that the babies of women with SSc are more likely to have low weight for gestational age. Also, data from previous studies have shown that patients with severe SSc disease, just like all patients with any illness in the connective tissue disease realm, need to be very cautious when considering pregnancy. As always, good communication between the patient and physician and good clinical judgment are paramount.
When physicians counsel patients about pregnancy, the discussion should include specifics of cardiac, pulmonary, gastrointestinal, and renal involvement as they relate to the patient’s condition. Other issues include family history, whether there are other children in the family, what kind of support systems the patient has, other medications needed to control disease, and the psychological status of the individual patient.
As for avenues for further research, larger prospective data sets are needed, including data on patients with concomitant illnesses, different medications, serologies, microchimerism, physiology, and genetics when possible. Of course, data are needed on both the short-term and long-term outcomes of the children as well as the mothers. In cases of poor outcomes, studies of tissue are warranted.
Dr. Daniel E. Furst is the Carl M. Pearson professor in rheumatology at the University of California, Los Angeles and a member of the Rheumatology News Editorial Advisory Board.
Dr. Furst has received research grants from multiple companies including Bristol-Myers Squibb, Celgene, Genentech, National Institutes of Health, and UCB. He has served as a consultant for multiple companies including Abbott, Bristol-Myers Squibb, Centocor, Novartis, and Xoma. He has served on the speaker's bureau for Abbott and Genentech, and has received honoraria from Abbott, Actelion, Bristol-Myers Squibb, Genentech, Encysive, and UCB.
Findings from this study and other studies on pregnancy in women with systemic sclerosis are important because many affected patients are in their child-bearing years.
This is one of several studies on the topic of SSc and pregnancy, and findings from the other studies do not agree fully with these data. Findings from other studies have shown that the babies of women with SSc are more likely to have low weight for gestational age. Also, data from previous studies have shown that patients with severe SSc disease, just like all patients with any illness in the connective tissue disease realm, need to be very cautious when considering pregnancy. As always, good communication between the patient and physician and good clinical judgment are paramount.
When physicians counsel patients about pregnancy, the discussion should include specifics of cardiac, pulmonary, gastrointestinal, and renal involvement as they relate to the patient’s condition. Other issues include family history, whether there are other children in the family, what kind of support systems the patient has, other medications needed to control disease, and the psychological status of the individual patient.
As for avenues for further research, larger prospective data sets are needed, including data on patients with concomitant illnesses, different medications, serologies, microchimerism, physiology, and genetics when possible. Of course, data are needed on both the short-term and long-term outcomes of the children as well as the mothers. In cases of poor outcomes, studies of tissue are warranted.
Dr. Daniel E. Furst is the Carl M. Pearson professor in rheumatology at the University of California, Los Angeles and a member of the Rheumatology News Editorial Advisory Board.
Dr. Furst has received research grants from multiple companies including Bristol-Myers Squibb, Celgene, Genentech, National Institutes of Health, and UCB. He has served as a consultant for multiple companies including Abbott, Bristol-Myers Squibb, Centocor, Novartis, and Xoma. He has served on the speaker's bureau for Abbott and Genentech, and has received honoraria from Abbott, Actelion, Bristol-Myers Squibb, Genentech, Encysive, and UCB.
Findings from this study and other studies on pregnancy in women with systemic sclerosis are important because many affected patients are in their child-bearing years.
This is one of several studies on the topic of SSc and pregnancy, and findings from the other studies do not agree fully with these data. Findings from other studies have shown that the babies of women with SSc are more likely to have low weight for gestational age. Also, data from previous studies have shown that patients with severe SSc disease, just like all patients with any illness in the connective tissue disease realm, need to be very cautious when considering pregnancy. As always, good communication between the patient and physician and good clinical judgment are paramount.
When physicians counsel patients about pregnancy, the discussion should include specifics of cardiac, pulmonary, gastrointestinal, and renal involvement as they relate to the patient’s condition. Other issues include family history, whether there are other children in the family, what kind of support systems the patient has, other medications needed to control disease, and the psychological status of the individual patient.
As for avenues for further research, larger prospective data sets are needed, including data on patients with concomitant illnesses, different medications, serologies, microchimerism, physiology, and genetics when possible. Of course, data are needed on both the short-term and long-term outcomes of the children as well as the mothers. In cases of poor outcomes, studies of tissue are warranted.
Dr. Daniel E. Furst is the Carl M. Pearson professor in rheumatology at the University of California, Los Angeles and a member of the Rheumatology News Editorial Advisory Board.
Dr. Furst has received research grants from multiple companies including Bristol-Myers Squibb, Celgene, Genentech, National Institutes of Health, and UCB. He has served as a consultant for multiple companies including Abbott, Bristol-Myers Squibb, Centocor, Novartis, and Xoma. He has served on the speaker's bureau for Abbott and Genentech, and has received honoraria from Abbott, Actelion, Bristol-Myers Squibb, Genentech, Encysive, and UCB.
Many women with systemic sclerosis can have successful pregnancies, but the rates of preterm birth, low birth weight, and intrauterine growth restriction are approximately twice as high in these women compared to the general population of pregnant women, based on data from 109 pregnancies in 99 women with systemic sclerosis.
The findings were published in Arthritis & Rheumatism (Arthritis Rheum. 2011 Dec. 28 [doi:10.1002/art.34350]).
Data from previous studies have suggested negative outcomes for pregnancies in women with systemic sclerosis (SSc), but these have been small case series or large database reviews that did not allow for the identification of individual patients, said Dr. Mara Taraborelli of Spedali Civili and University, Brescia, Italy, and colleagues.
In this prospective study, the researchers followed 99 women with SSc who had 109 pregnancies between 2000 and 2011. The women attended one of 25 participating research centers in Italy.
The average age at conception was 32 years, and most of the women were white. A total of 107 pregnancies were spontaneous, and 2 were achieved with assisted reproductive techniques.
Preterm deliveries were significantly more common in the SSc women, compared to the general obstetric population that served as a control group (25% vs. 12%, respectively). Severe preterm delivery (defined as delivery at less than 34 weeks) also was significantly more common in SSc women, compared to the controls (10% vs. 5%, respectively).
In addition, very low birth weight babies and cases of intrauterine growth restriction were significantly more common in the SSc women, compared to the controls (5% vs. 1%, respectively, and 6% vs. 1%, respectively).
The researchers found no increase in hypertensive disorders of pregnancy or spontaneous pregnancy losses in SSc women, compared to the general pregnant population.
"We observed a low rate of disease progression shortly after the end of pregnancy; this risk might be greater in aSCL-70 positive patients with recent-onset disease," the researchers noted. All four cases of internal organ disease evolution within 12 months after delivery occurred in women who were aSCL-70 positive, and 3 of 23 (13%) of women who were aSCL-70 positive whose disease had lasted less than 3 years had some disease progression after delivery.
A total of six newborns spent a median of 15 days in the intensive care unit. Of these, one was severely premature and died of multi-organ failure.
The study findings were limited by the use of retrospective analysis and the use of controls for only one year, but the results suggest that successful pregnancies are possible for SSc women despite the increased risks for poor maternal and fetal outcomes, with multidisciplinary management, the researchers said. However, pregnancy may not be advisable for patients with severe organ damage or recent onset of SSc, especially those who are antitopoisomerase positive, they added.
The researchers had no financial conflicts to disclose. The study was supported in part by three patients’ associations: the Gruppo Italiano Lotta alla Sclerodermia, Gruppo Lupus Eritematoso Sistemico Lombardia, and the Associazone Lombarda Malati Reumatici.
Many women with systemic sclerosis can have successful pregnancies, but the rates of preterm birth, low birth weight, and intrauterine growth restriction are approximately twice as high in these women compared to the general population of pregnant women, based on data from 109 pregnancies in 99 women with systemic sclerosis.
The findings were published in Arthritis & Rheumatism (Arthritis Rheum. 2011 Dec. 28 [doi:10.1002/art.34350]).
Data from previous studies have suggested negative outcomes for pregnancies in women with systemic sclerosis (SSc), but these have been small case series or large database reviews that did not allow for the identification of individual patients, said Dr. Mara Taraborelli of Spedali Civili and University, Brescia, Italy, and colleagues.
In this prospective study, the researchers followed 99 women with SSc who had 109 pregnancies between 2000 and 2011. The women attended one of 25 participating research centers in Italy.
The average age at conception was 32 years, and most of the women were white. A total of 107 pregnancies were spontaneous, and 2 were achieved with assisted reproductive techniques.
Preterm deliveries were significantly more common in the SSc women, compared to the general obstetric population that served as a control group (25% vs. 12%, respectively). Severe preterm delivery (defined as delivery at less than 34 weeks) also was significantly more common in SSc women, compared to the controls (10% vs. 5%, respectively).
In addition, very low birth weight babies and cases of intrauterine growth restriction were significantly more common in the SSc women, compared to the controls (5% vs. 1%, respectively, and 6% vs. 1%, respectively).
The researchers found no increase in hypertensive disorders of pregnancy or spontaneous pregnancy losses in SSc women, compared to the general pregnant population.
"We observed a low rate of disease progression shortly after the end of pregnancy; this risk might be greater in aSCL-70 positive patients with recent-onset disease," the researchers noted. All four cases of internal organ disease evolution within 12 months after delivery occurred in women who were aSCL-70 positive, and 3 of 23 (13%) of women who were aSCL-70 positive whose disease had lasted less than 3 years had some disease progression after delivery.
A total of six newborns spent a median of 15 days in the intensive care unit. Of these, one was severely premature and died of multi-organ failure.
The study findings were limited by the use of retrospective analysis and the use of controls for only one year, but the results suggest that successful pregnancies are possible for SSc women despite the increased risks for poor maternal and fetal outcomes, with multidisciplinary management, the researchers said. However, pregnancy may not be advisable for patients with severe organ damage or recent onset of SSc, especially those who are antitopoisomerase positive, they added.
The researchers had no financial conflicts to disclose. The study was supported in part by three patients’ associations: the Gruppo Italiano Lotta alla Sclerodermia, Gruppo Lupus Eritematoso Sistemico Lombardia, and the Associazone Lombarda Malati Reumatici.
FROM ARTHRITIS & RHEUMATISM
Major Finding: Preterm deliveries were twice as common in pregnant women with systemic sclerosis, compared with pregnant women in the general population (25% vs. 12%, respectively).
Data Source: A prospective study of 99 women with systemic sclerosis.
Disclosures: The researchers had no financial conflicts to disclose. The study was supported in part by three patients’ associations: the Gruppo Italiano Lotta alla Sclerodermia, Gruppo Lupus Eritematoso Sistemico Lombardia, and the Associazone Lombarda Malati Reumatici.
The Whys and How of Stopping Biologics
The vast majority of medical talks on biologic therapy for psoriasis focus on starting and maintaining the medications. Stopping biologics is a seldom-discussed topic, yet one that physicians often need to address.
"We’ve all got patients who are on biologic therapy who are completely clear of their psoriasis, and you’re constantly wondering, ‘Should I stop the biologic? Do they need to have that treatment anymore? Can I reduce the dosing frequency?’ The simplest answer is that in most cases, it’s probably not a good idea to stop unless there’s a good reason for doing so. It has been shown in most of the big clinical trials that if you stop therapy, the psoriasis will relapse at some point," Dr. Christopher Griffiths said at the annual congress of the European Academy of Dermatology and Venereology.
"With long-term therapy beyond 6-12 months, can biologics be stopped or produce remission? In most cases, no. And there’s no biomarker for disease activity as of yet to guide us," added Dr. Griffiths, professor of dermatology and associate dean for research at the University of Manchester (England).
Compelling reasons to stop biologic therapy include failure to achieve or maintain significant clinical improvement, serious adverse events, impending elective major surgery, certain vaccinations, and pregnancy. Dr. Griffiths highlighted the following points:
• Lack of Effectiveness. Today’s biologics are not curative. In a recent French report, only 31 of 86 psoriasis patients (36%) who started on etanercept (Enbrel), infliximab (Remicade), or efalizumab were still on the same biologic agent 24 months later (J. Dermatol. Treat. 2011;22:151-2). Similarly, the Danish national psoriasis database experience has been that roughly 40% of patients started on etanercept or adalimumab (Humira) were still on the medication 4 years later, as were 70% of those who started on infliximab (Br. J. Dermatol. 2011;164:1091-6).
The good news, Dr. Griffiths continued, is that lack of effectiveness for anti–tumor necrosis factor agents is not a class effect. He and his coinvestigators have reported that 21 of 31 psoriasis patients who switched to adalimumab from another anti-TNF biologic for lack of efficacy met the NICE (U.K. National Institute for Health and Clinical Excellence) criteria for adalimumab treatment continuation at 16 weeks (Br. J. Dermatol. 2010;163:859-62).
"Each anti-TNF drug is different, so if you fail one it doesn’t mean you’re going to fail another. That’s a very important point, and a very strong argument in your favor when dealing with payers. And it’s an observation that can only come from real-life data from a cohort study; you’re not going to get that information from clinical trials," the dermatologist explained.
The NICE criteria for continuation of biologic therapy bring an element of strict objectivity to treatment decision making in a rationed health care system. For British psoriasis patients to continue on a given biologic agent, they have to demonstrate a PASI 75 response (that is, a 75% improvement over the baseline Psoriasis Area and Severity Index score) at 16 weeks, or a PASI 50 response plus a 5-point drop in the Dermatology Life Quality Index (DLQI).
When physicians switch biologics, Dr. Griffiths recommends that they skip a lengthy washout period because of the associated risk of a severe, hard-to-control flare. His practice is to stop one and start another.
• Major Elective Surgery. There is a dearth of data on stopping biologics in psoriasis patients who plan to undergo elective surgery. The best practice for now, in Dr. Griffiths’ view, is to follow the British Society for Rheumatology guidance, which is based on an extensive biologics register the group maintains for rheumatoid arthritis.
The rheumatologists’ advice is to halt effective biologic therapy only for truly major surgery, and to stop anti-TNF drugs more than four half-lives before the operation. That’s 2-3 weeks beforehand for etanercept, 6-8 weeks for adalimumab, and 4-6 weeks for infliximab. There are no firm data for ustekinumab (Stelara) as yet, but experts advise halting it 12 weeks before surgery. Biologic therapy should be resumed as soon as possible postoperatively.
• Pregnancy. Again, a paucity of data exists on biologics for psoriasis in pregnancy. But the data accumulating in the British Society for Rheumatology Biologics Register (BSRBR) is reassuring. Although the rheumatologists recommend that pregnancy be avoided in patients on biologics, the experience to date in pregnant rheumatoid arthritis patients suggests there is little to no risk to the fetus. Breastfeeding should be avoided by women on biologic therapy other than infliximab, which is not excreted in breast milk, Dr. Griffiths continued.
• Vaccinations. British Association of Dermatologists guidelines on the use of biologics for psoriasis (Br. J. Dermatol. 2009;161:987-1019), which Dr. Griffiths coauthored and which will be updated in late 2012, recommend avoiding giving live or attenuated virus vaccines within 2 weeks prior to starting a patient on biologic therapy, or while the patient is on a biologic, or for up to 6 months after the patient stops the biologic. Inactivated virus vaccines are safe for patients on biologic therapy, although the antibody response will be somewhat less robust in a patient on an anti-TNF agent than in other individuals.
"But we advise – as should you – that all patients on biologics should receive influenza and pneumococcal vaccines. It’s just good clinical practice because these patients are by definition in a high-risk category," he said.
• Stopping and Restarting Biologics. It’s well established that etanercept can be used intermittently with good results. That is, a patient might use etanercept to good effect for 6 months, stop it, then restart when relapse occurs, and the agent will still remain effective. The same typically holds true for alefacept (Amevive).
In contrast, infliximab can realistically be used for only a single course of treatment. If a patient goes off the drug and later goes back on it, the chances of regaining a response are very low because of the formation of blocking antibodies.
The picture regarding the intermittent use of adalimumab is less clear. There are documented cases in which this agent hasn’t been effective any longer upon second usage.
There is good new evidence, presented by Dr. Griffiths elsewhere during the congress, that ustekinumab can be restarted after a hiatus with very good results.
Dr. Griffiths disclosed that he serves on the advisory boards for and has received research grants from numerous pharmaceutical companies.
The vast majority of medical talks on biologic therapy for psoriasis focus on starting and maintaining the medications. Stopping biologics is a seldom-discussed topic, yet one that physicians often need to address.
"We’ve all got patients who are on biologic therapy who are completely clear of their psoriasis, and you’re constantly wondering, ‘Should I stop the biologic? Do they need to have that treatment anymore? Can I reduce the dosing frequency?’ The simplest answer is that in most cases, it’s probably not a good idea to stop unless there’s a good reason for doing so. It has been shown in most of the big clinical trials that if you stop therapy, the psoriasis will relapse at some point," Dr. Christopher Griffiths said at the annual congress of the European Academy of Dermatology and Venereology.
"With long-term therapy beyond 6-12 months, can biologics be stopped or produce remission? In most cases, no. And there’s no biomarker for disease activity as of yet to guide us," added Dr. Griffiths, professor of dermatology and associate dean for research at the University of Manchester (England).
Compelling reasons to stop biologic therapy include failure to achieve or maintain significant clinical improvement, serious adverse events, impending elective major surgery, certain vaccinations, and pregnancy. Dr. Griffiths highlighted the following points:
• Lack of Effectiveness. Today’s biologics are not curative. In a recent French report, only 31 of 86 psoriasis patients (36%) who started on etanercept (Enbrel), infliximab (Remicade), or efalizumab were still on the same biologic agent 24 months later (J. Dermatol. Treat. 2011;22:151-2). Similarly, the Danish national psoriasis database experience has been that roughly 40% of patients started on etanercept or adalimumab (Humira) were still on the medication 4 years later, as were 70% of those who started on infliximab (Br. J. Dermatol. 2011;164:1091-6).
The good news, Dr. Griffiths continued, is that lack of effectiveness for anti–tumor necrosis factor agents is not a class effect. He and his coinvestigators have reported that 21 of 31 psoriasis patients who switched to adalimumab from another anti-TNF biologic for lack of efficacy met the NICE (U.K. National Institute for Health and Clinical Excellence) criteria for adalimumab treatment continuation at 16 weeks (Br. J. Dermatol. 2010;163:859-62).
"Each anti-TNF drug is different, so if you fail one it doesn’t mean you’re going to fail another. That’s a very important point, and a very strong argument in your favor when dealing with payers. And it’s an observation that can only come from real-life data from a cohort study; you’re not going to get that information from clinical trials," the dermatologist explained.
The NICE criteria for continuation of biologic therapy bring an element of strict objectivity to treatment decision making in a rationed health care system. For British psoriasis patients to continue on a given biologic agent, they have to demonstrate a PASI 75 response (that is, a 75% improvement over the baseline Psoriasis Area and Severity Index score) at 16 weeks, or a PASI 50 response plus a 5-point drop in the Dermatology Life Quality Index (DLQI).
When physicians switch biologics, Dr. Griffiths recommends that they skip a lengthy washout period because of the associated risk of a severe, hard-to-control flare. His practice is to stop one and start another.
• Major Elective Surgery. There is a dearth of data on stopping biologics in psoriasis patients who plan to undergo elective surgery. The best practice for now, in Dr. Griffiths’ view, is to follow the British Society for Rheumatology guidance, which is based on an extensive biologics register the group maintains for rheumatoid arthritis.
The rheumatologists’ advice is to halt effective biologic therapy only for truly major surgery, and to stop anti-TNF drugs more than four half-lives before the operation. That’s 2-3 weeks beforehand for etanercept, 6-8 weeks for adalimumab, and 4-6 weeks for infliximab. There are no firm data for ustekinumab (Stelara) as yet, but experts advise halting it 12 weeks before surgery. Biologic therapy should be resumed as soon as possible postoperatively.
• Pregnancy. Again, a paucity of data exists on biologics for psoriasis in pregnancy. But the data accumulating in the British Society for Rheumatology Biologics Register (BSRBR) is reassuring. Although the rheumatologists recommend that pregnancy be avoided in patients on biologics, the experience to date in pregnant rheumatoid arthritis patients suggests there is little to no risk to the fetus. Breastfeeding should be avoided by women on biologic therapy other than infliximab, which is not excreted in breast milk, Dr. Griffiths continued.
• Vaccinations. British Association of Dermatologists guidelines on the use of biologics for psoriasis (Br. J. Dermatol. 2009;161:987-1019), which Dr. Griffiths coauthored and which will be updated in late 2012, recommend avoiding giving live or attenuated virus vaccines within 2 weeks prior to starting a patient on biologic therapy, or while the patient is on a biologic, or for up to 6 months after the patient stops the biologic. Inactivated virus vaccines are safe for patients on biologic therapy, although the antibody response will be somewhat less robust in a patient on an anti-TNF agent than in other individuals.
"But we advise – as should you – that all patients on biologics should receive influenza and pneumococcal vaccines. It’s just good clinical practice because these patients are by definition in a high-risk category," he said.
• Stopping and Restarting Biologics. It’s well established that etanercept can be used intermittently with good results. That is, a patient might use etanercept to good effect for 6 months, stop it, then restart when relapse occurs, and the agent will still remain effective. The same typically holds true for alefacept (Amevive).
In contrast, infliximab can realistically be used for only a single course of treatment. If a patient goes off the drug and later goes back on it, the chances of regaining a response are very low because of the formation of blocking antibodies.
The picture regarding the intermittent use of adalimumab is less clear. There are documented cases in which this agent hasn’t been effective any longer upon second usage.
There is good new evidence, presented by Dr. Griffiths elsewhere during the congress, that ustekinumab can be restarted after a hiatus with very good results.
Dr. Griffiths disclosed that he serves on the advisory boards for and has received research grants from numerous pharmaceutical companies.
The vast majority of medical talks on biologic therapy for psoriasis focus on starting and maintaining the medications. Stopping biologics is a seldom-discussed topic, yet one that physicians often need to address.
"We’ve all got patients who are on biologic therapy who are completely clear of their psoriasis, and you’re constantly wondering, ‘Should I stop the biologic? Do they need to have that treatment anymore? Can I reduce the dosing frequency?’ The simplest answer is that in most cases, it’s probably not a good idea to stop unless there’s a good reason for doing so. It has been shown in most of the big clinical trials that if you stop therapy, the psoriasis will relapse at some point," Dr. Christopher Griffiths said at the annual congress of the European Academy of Dermatology and Venereology.
"With long-term therapy beyond 6-12 months, can biologics be stopped or produce remission? In most cases, no. And there’s no biomarker for disease activity as of yet to guide us," added Dr. Griffiths, professor of dermatology and associate dean for research at the University of Manchester (England).
Compelling reasons to stop biologic therapy include failure to achieve or maintain significant clinical improvement, serious adverse events, impending elective major surgery, certain vaccinations, and pregnancy. Dr. Griffiths highlighted the following points:
• Lack of Effectiveness. Today’s biologics are not curative. In a recent French report, only 31 of 86 psoriasis patients (36%) who started on etanercept (Enbrel), infliximab (Remicade), or efalizumab were still on the same biologic agent 24 months later (J. Dermatol. Treat. 2011;22:151-2). Similarly, the Danish national psoriasis database experience has been that roughly 40% of patients started on etanercept or adalimumab (Humira) were still on the medication 4 years later, as were 70% of those who started on infliximab (Br. J. Dermatol. 2011;164:1091-6).
The good news, Dr. Griffiths continued, is that lack of effectiveness for anti–tumor necrosis factor agents is not a class effect. He and his coinvestigators have reported that 21 of 31 psoriasis patients who switched to adalimumab from another anti-TNF biologic for lack of efficacy met the NICE (U.K. National Institute for Health and Clinical Excellence) criteria for adalimumab treatment continuation at 16 weeks (Br. J. Dermatol. 2010;163:859-62).
"Each anti-TNF drug is different, so if you fail one it doesn’t mean you’re going to fail another. That’s a very important point, and a very strong argument in your favor when dealing with payers. And it’s an observation that can only come from real-life data from a cohort study; you’re not going to get that information from clinical trials," the dermatologist explained.
The NICE criteria for continuation of biologic therapy bring an element of strict objectivity to treatment decision making in a rationed health care system. For British psoriasis patients to continue on a given biologic agent, they have to demonstrate a PASI 75 response (that is, a 75% improvement over the baseline Psoriasis Area and Severity Index score) at 16 weeks, or a PASI 50 response plus a 5-point drop in the Dermatology Life Quality Index (DLQI).
When physicians switch biologics, Dr. Griffiths recommends that they skip a lengthy washout period because of the associated risk of a severe, hard-to-control flare. His practice is to stop one and start another.
• Major Elective Surgery. There is a dearth of data on stopping biologics in psoriasis patients who plan to undergo elective surgery. The best practice for now, in Dr. Griffiths’ view, is to follow the British Society for Rheumatology guidance, which is based on an extensive biologics register the group maintains for rheumatoid arthritis.
The rheumatologists’ advice is to halt effective biologic therapy only for truly major surgery, and to stop anti-TNF drugs more than four half-lives before the operation. That’s 2-3 weeks beforehand for etanercept, 6-8 weeks for adalimumab, and 4-6 weeks for infliximab. There are no firm data for ustekinumab (Stelara) as yet, but experts advise halting it 12 weeks before surgery. Biologic therapy should be resumed as soon as possible postoperatively.
• Pregnancy. Again, a paucity of data exists on biologics for psoriasis in pregnancy. But the data accumulating in the British Society for Rheumatology Biologics Register (BSRBR) is reassuring. Although the rheumatologists recommend that pregnancy be avoided in patients on biologics, the experience to date in pregnant rheumatoid arthritis patients suggests there is little to no risk to the fetus. Breastfeeding should be avoided by women on biologic therapy other than infliximab, which is not excreted in breast milk, Dr. Griffiths continued.
• Vaccinations. British Association of Dermatologists guidelines on the use of biologics for psoriasis (Br. J. Dermatol. 2009;161:987-1019), which Dr. Griffiths coauthored and which will be updated in late 2012, recommend avoiding giving live or attenuated virus vaccines within 2 weeks prior to starting a patient on biologic therapy, or while the patient is on a biologic, or for up to 6 months after the patient stops the biologic. Inactivated virus vaccines are safe for patients on biologic therapy, although the antibody response will be somewhat less robust in a patient on an anti-TNF agent than in other individuals.
"But we advise – as should you – that all patients on biologics should receive influenza and pneumococcal vaccines. It’s just good clinical practice because these patients are by definition in a high-risk category," he said.
• Stopping and Restarting Biologics. It’s well established that etanercept can be used intermittently with good results. That is, a patient might use etanercept to good effect for 6 months, stop it, then restart when relapse occurs, and the agent will still remain effective. The same typically holds true for alefacept (Amevive).
In contrast, infliximab can realistically be used for only a single course of treatment. If a patient goes off the drug and later goes back on it, the chances of regaining a response are very low because of the formation of blocking antibodies.
The picture regarding the intermittent use of adalimumab is less clear. There are documented cases in which this agent hasn’t been effective any longer upon second usage.
There is good new evidence, presented by Dr. Griffiths elsewhere during the congress, that ustekinumab can be restarted after a hiatus with very good results.
Dr. Griffiths disclosed that he serves on the advisory boards for and has received research grants from numerous pharmaceutical companies.
Blog: Top 10 Stories of 2011
For those of you who have had a busy year and haven't had the chance to regularly read the latest dermatology news on Skin and Allergy News Digital Network, we have you covered. As we ring in the new year, here's a rundown of last year's most-viewed stories:
10. Experts: Medical Dermatology Is Losing Ground, By Bruce Jancin: Experts in medical dermatology predicted the specialty will become narrower and less medically oriented by 2020. As we enter 2012, some experts said they were concerned about the emphasis on aesthetic dermatology and dermatologic surgery.
9. Mohs Surgery in Medicare Patients Skyrocketing, By Sherry Boschert: Several Mohs surgery experts found that the rate of Mohs surgery per 1,000 Medicare beneficiaries increased by 236% between 1999 and 2009. Dr. Matthew Donaldson and his associates presented the data at the annual meeting of the American College of Mohs Surgery.
8. Blog: New Isotretinoin Drug May Address Safety Concerns, By Amy Pfeiffer: This much-viewed blog post highlighted an investigational isotretinoin drug that may eliminate safety concerns associated with the drug, like IBD and depression. The gelatin capsules of CIP-iisotretinoin help reduce GI irritation and the drug is less food dependent.
7. Dosing Isotretinoin: Go Big to Avoid Second Course, By Jeffrey Eisenberg: In another isotretinoin study, investigators found that patients receiving a higher cumulative dose of the drug were no less likely to experience an acne relapse than those who received a lower cumulative dose. However, the investigators found that patients treated with a higher dose were less likely to need a second course of treatment.
6. Knifelike Vulvar Ulcers May Signal Crohn's Disease, By Kate Johnson: Knifelike vulvar ulcers could be a sign of Crohn's disease in women, according to experts at a conference on vulvovaginal diseases. For some patients, ulcers may be the only manifestation of the disorder.
5. Biologics Up Cardiovascular Risk, New Analysis Finds, By Sherry Boschert: Biologic therapies used to treat psoriasis have been linked to an increase in major cardiovascular events, according to researchers. One patient on placebo developed a major cardiovascular event in a study of etanercept. Five patients on ustekinumab, five on briakinumab, and one on adalimumab also developed major cardiovascular events.
4. Future Technologies Hold Promise for Hair Restoration, By Damian McNamara: At an annual meeting of dermatologic surgeons, Dr. Ricardo Mejia discussed technological advancements in hair restoration. He said the future for hair restoration could include technologies like robotic hair transfer, hair cloning, and technologies to optimize new growth.
3. AAD: Potential Doxycycline, IBD Link Considered Worrisome, By Bruce Jancin: In more acne news, a retrospective cohort study linked tetracycline-class antibiotics with an increase in inflammatory bowel disease. The highly controversial findings were one of the hottest topics at the annual meeting of the American Academy of Dermatology and on this website.
2. Bimatoprost Repigments Vitiligo Patient Skin, By Bruce Jancin: A topical bimatoprost ophthalmic solution could serve as treatment for focal vitiligo, according to a pilot study presented at the World Congress of Dermatology. Researchers said 7 out of 10 patients exhibited pronounced repigmentation after 2 months of treatment.
1. Marijuana Allergies "Fairly Common," Expert Says, By M. Alexander Otto: A heads up to physicians: allergy experts said marijuana allergies are more common than most people think. Patients with with a marijuana allergy exhibit symptoms including wheezing, sinusitis, throat swelling, and inhalation issues.
Best wishes for 2012!
-- Frances Correa (FMCReporting)
For those of you who have had a busy year and haven't had the chance to regularly read the latest dermatology news on Skin and Allergy News Digital Network, we have you covered. As we ring in the new year, here's a rundown of last year's most-viewed stories:
10. Experts: Medical Dermatology Is Losing Ground, By Bruce Jancin: Experts in medical dermatology predicted the specialty will become narrower and less medically oriented by 2020. As we enter 2012, some experts said they were concerned about the emphasis on aesthetic dermatology and dermatologic surgery.
9. Mohs Surgery in Medicare Patients Skyrocketing, By Sherry Boschert: Several Mohs surgery experts found that the rate of Mohs surgery per 1,000 Medicare beneficiaries increased by 236% between 1999 and 2009. Dr. Matthew Donaldson and his associates presented the data at the annual meeting of the American College of Mohs Surgery.
8. Blog: New Isotretinoin Drug May Address Safety Concerns, By Amy Pfeiffer: This much-viewed blog post highlighted an investigational isotretinoin drug that may eliminate safety concerns associated with the drug, like IBD and depression. The gelatin capsules of CIP-iisotretinoin help reduce GI irritation and the drug is less food dependent.
7. Dosing Isotretinoin: Go Big to Avoid Second Course, By Jeffrey Eisenberg: In another isotretinoin study, investigators found that patients receiving a higher cumulative dose of the drug were no less likely to experience an acne relapse than those who received a lower cumulative dose. However, the investigators found that patients treated with a higher dose were less likely to need a second course of treatment.
6. Knifelike Vulvar Ulcers May Signal Crohn's Disease, By Kate Johnson: Knifelike vulvar ulcers could be a sign of Crohn's disease in women, according to experts at a conference on vulvovaginal diseases. For some patients, ulcers may be the only manifestation of the disorder.
5. Biologics Up Cardiovascular Risk, New Analysis Finds, By Sherry Boschert: Biologic therapies used to treat psoriasis have been linked to an increase in major cardiovascular events, according to researchers. One patient on placebo developed a major cardiovascular event in a study of etanercept. Five patients on ustekinumab, five on briakinumab, and one on adalimumab also developed major cardiovascular events.
4. Future Technologies Hold Promise for Hair Restoration, By Damian McNamara: At an annual meeting of dermatologic surgeons, Dr. Ricardo Mejia discussed technological advancements in hair restoration. He said the future for hair restoration could include technologies like robotic hair transfer, hair cloning, and technologies to optimize new growth.
3. AAD: Potential Doxycycline, IBD Link Considered Worrisome, By Bruce Jancin: In more acne news, a retrospective cohort study linked tetracycline-class antibiotics with an increase in inflammatory bowel disease. The highly controversial findings were one of the hottest topics at the annual meeting of the American Academy of Dermatology and on this website.
2. Bimatoprost Repigments Vitiligo Patient Skin, By Bruce Jancin: A topical bimatoprost ophthalmic solution could serve as treatment for focal vitiligo, according to a pilot study presented at the World Congress of Dermatology. Researchers said 7 out of 10 patients exhibited pronounced repigmentation after 2 months of treatment.
1. Marijuana Allergies "Fairly Common," Expert Says, By M. Alexander Otto: A heads up to physicians: allergy experts said marijuana allergies are more common than most people think. Patients with with a marijuana allergy exhibit symptoms including wheezing, sinusitis, throat swelling, and inhalation issues.
Best wishes for 2012!
-- Frances Correa (FMCReporting)
For those of you who have had a busy year and haven't had the chance to regularly read the latest dermatology news on Skin and Allergy News Digital Network, we have you covered. As we ring in the new year, here's a rundown of last year's most-viewed stories:
10. Experts: Medical Dermatology Is Losing Ground, By Bruce Jancin: Experts in medical dermatology predicted the specialty will become narrower and less medically oriented by 2020. As we enter 2012, some experts said they were concerned about the emphasis on aesthetic dermatology and dermatologic surgery.
9. Mohs Surgery in Medicare Patients Skyrocketing, By Sherry Boschert: Several Mohs surgery experts found that the rate of Mohs surgery per 1,000 Medicare beneficiaries increased by 236% between 1999 and 2009. Dr. Matthew Donaldson and his associates presented the data at the annual meeting of the American College of Mohs Surgery.
8. Blog: New Isotretinoin Drug May Address Safety Concerns, By Amy Pfeiffer: This much-viewed blog post highlighted an investigational isotretinoin drug that may eliminate safety concerns associated with the drug, like IBD and depression. The gelatin capsules of CIP-iisotretinoin help reduce GI irritation and the drug is less food dependent.
7. Dosing Isotretinoin: Go Big to Avoid Second Course, By Jeffrey Eisenberg: In another isotretinoin study, investigators found that patients receiving a higher cumulative dose of the drug were no less likely to experience an acne relapse than those who received a lower cumulative dose. However, the investigators found that patients treated with a higher dose were less likely to need a second course of treatment.
6. Knifelike Vulvar Ulcers May Signal Crohn's Disease, By Kate Johnson: Knifelike vulvar ulcers could be a sign of Crohn's disease in women, according to experts at a conference on vulvovaginal diseases. For some patients, ulcers may be the only manifestation of the disorder.
5. Biologics Up Cardiovascular Risk, New Analysis Finds, By Sherry Boschert: Biologic therapies used to treat psoriasis have been linked to an increase in major cardiovascular events, according to researchers. One patient on placebo developed a major cardiovascular event in a study of etanercept. Five patients on ustekinumab, five on briakinumab, and one on adalimumab also developed major cardiovascular events.
4. Future Technologies Hold Promise for Hair Restoration, By Damian McNamara: At an annual meeting of dermatologic surgeons, Dr. Ricardo Mejia discussed technological advancements in hair restoration. He said the future for hair restoration could include technologies like robotic hair transfer, hair cloning, and technologies to optimize new growth.
3. AAD: Potential Doxycycline, IBD Link Considered Worrisome, By Bruce Jancin: In more acne news, a retrospective cohort study linked tetracycline-class antibiotics with an increase in inflammatory bowel disease. The highly controversial findings were one of the hottest topics at the annual meeting of the American Academy of Dermatology and on this website.
2. Bimatoprost Repigments Vitiligo Patient Skin, By Bruce Jancin: A topical bimatoprost ophthalmic solution could serve as treatment for focal vitiligo, according to a pilot study presented at the World Congress of Dermatology. Researchers said 7 out of 10 patients exhibited pronounced repigmentation after 2 months of treatment.
1. Marijuana Allergies "Fairly Common," Expert Says, By M. Alexander Otto: A heads up to physicians: allergy experts said marijuana allergies are more common than most people think. Patients with with a marijuana allergy exhibit symptoms including wheezing, sinusitis, throat swelling, and inhalation issues.
Best wishes for 2012!
-- Frances Correa (FMCReporting)
Evidence Builds for Switching Biologics After Psoriasis Treatment Failure
LAS VEGAS – Emerging data support the practice of switching biologic agents after an initial biologic therapy fails in psoriasis, and even the possibility of rotating back to a biologic that didn’t work previously, according to Dr. Francisco Kerdel, director of the dermatology inpatient service at the University of Miami Hospital.
In one recent series of 747 psoriasis patients on biologics, the 4-year drug response was in the range of 40% for etanercept or adalimumab and 70% for infliximab (Br. J. Dermatol. 2011;164:1091-6). "Thus, there is a logical need for ‘switching’ [biologic] therapy," he noted at the SDEF Las Vegas Dermatology Seminar.
The reasons for treatment failure are not known. Antibody production has been suspected of playing a role, but the presence of antibodies seldom correlates with clinical response, he said.
In a 16-week, open-label trial, a Physician Global Assessment (PGA) rating of "clear" or "minimal" was achieved in 52% of 152 patients who had chronic plaque psoriasis and were switched to adalimumab following suboptimal responses to etanercept, methotrexate, or phototherapy (J. Am. Acad. Dermatol. 2011;64:671-81).
In the PSUNRISE study (a prospective, multicenter, open-label study of infliximab treatment in 215 patients with plaque psoriasis who had had a prior inadequate response to etanercept), a PGA score of 0 (clear) or 1 was achieved by week 10 in 65% of the 179 completers, and 60% remained at PGA 0-1 in weeks 14-26. These data have been submitted for publication, according to Dr. Kerdel, who was one of the study authors.
Good to excellent responses were achieved with ustekinumab at doses of either 45 mg or 90 mg, depending on body weight, in 9 of 11 psoriasis patients who had experienced treatment failures on multiple biologics, including infliximab (11 patients), etanercept (10), efalizumab (9), adalimumab (7), and golimumab (3) (Int. J. Dermatol. 2011;50:478-82).
There is even some evidence that patients can return with success to a biologic therapy that they had previously failed.
Dr. Kerdel and his associates have conducted an open-label study of etanercept re-treatment in 20 patients with moderate to severe psoriasis (defined as a PGA score of 3 or greater) who had had prior therapy with etanercept for a minimum of 6 months but had discontinued it because of loss of efficacy. The 10 men and 10 women had an average age of 49 years, with an average of 3.5 years between stopping and restarting etanercept. Five patients withdrew and were classified as treatment failures, regardless of the reason for withdrawal.
The proportion of responders (defined as those achieving a PGA score of 0 or 1) was 5 of 20 (25%) at week 8, and 8 of 20 (40%) at week 12. Body weight appeared to play a role. Among the 14 patients who had a PGA score of 2 or less at week 12, the average weight was 198.4 pounds, compared with 217.6 pounds for the 6 who did not have that response.
These preliminary findings suggest that rotational therapy is possible, at least in cases of secondary failure with etanercept. Rotational therapy may be possible with other biologics as well, but further studies are necessary, Dr. Kerdel concluded.
It had been thought that this practice would be of limited value because of the development of circulating antibodies, which were found in one study to range in prevalence from 5% of rheumatoid arthritis patients on ustekinumab to 87% of those treated with adalimumab (Clin. Rev. Allergy Immunol. 2010;38:82-9). However, the therapeutic relevance of non-neutralizing vs. neutralizing antibodies is currently unknown, he said.
In a recent prospective cohort study of 272 RA patients treated with adalimumab, 28% had developed antiadalimumab antibodies, which appeared within the first 28 weeks of treatment in two-thirds of them. Over 3 years of follow-up, 38% of the patients with antibodies discontinued adalimumab therapy because of treatment failure, compared with 14% of those who did not develop antibodies. Minimal disease activity was achieved in 48% without antibodies, compared with 13% who had antibodies (JAMA 2011;305:1460-8).
And in a retrospective observational study of 97 psoriasis patients who had been treated with anti–tumor necrosis factor–alpha therapy (60 on a first agent, 22 having failed one agent, 9 having failed two agents, and 6 having failed all three agents), antinuclear antibodies developed in 17%, 54%, 78% and 83%, respectively (Br. J. Dermatol. 2010;162:780-5). "So, antibodies do seem to play a role" in treatment failure, Dr. Kerdel commented.
Dr. Kerdel disclosed that he has been involved in clinical studies, has participated in advisory boards, and is a speaker for Amgen, Abbott, Janssen, Genentech, Astellas, Stiefel, Pfizer, Merck, Novartis, Eisai, and Celgene. SDEF and this news organization are owned by Elsevier.
LAS VEGAS – Emerging data support the practice of switching biologic agents after an initial biologic therapy fails in psoriasis, and even the possibility of rotating back to a biologic that didn’t work previously, according to Dr. Francisco Kerdel, director of the dermatology inpatient service at the University of Miami Hospital.
In one recent series of 747 psoriasis patients on biologics, the 4-year drug response was in the range of 40% for etanercept or adalimumab and 70% for infliximab (Br. J. Dermatol. 2011;164:1091-6). "Thus, there is a logical need for ‘switching’ [biologic] therapy," he noted at the SDEF Las Vegas Dermatology Seminar.
The reasons for treatment failure are not known. Antibody production has been suspected of playing a role, but the presence of antibodies seldom correlates with clinical response, he said.
In a 16-week, open-label trial, a Physician Global Assessment (PGA) rating of "clear" or "minimal" was achieved in 52% of 152 patients who had chronic plaque psoriasis and were switched to adalimumab following suboptimal responses to etanercept, methotrexate, or phototherapy (J. Am. Acad. Dermatol. 2011;64:671-81).
In the PSUNRISE study (a prospective, multicenter, open-label study of infliximab treatment in 215 patients with plaque psoriasis who had had a prior inadequate response to etanercept), a PGA score of 0 (clear) or 1 was achieved by week 10 in 65% of the 179 completers, and 60% remained at PGA 0-1 in weeks 14-26. These data have been submitted for publication, according to Dr. Kerdel, who was one of the study authors.
Good to excellent responses were achieved with ustekinumab at doses of either 45 mg or 90 mg, depending on body weight, in 9 of 11 psoriasis patients who had experienced treatment failures on multiple biologics, including infliximab (11 patients), etanercept (10), efalizumab (9), adalimumab (7), and golimumab (3) (Int. J. Dermatol. 2011;50:478-82).
There is even some evidence that patients can return with success to a biologic therapy that they had previously failed.
Dr. Kerdel and his associates have conducted an open-label study of etanercept re-treatment in 20 patients with moderate to severe psoriasis (defined as a PGA score of 3 or greater) who had had prior therapy with etanercept for a minimum of 6 months but had discontinued it because of loss of efficacy. The 10 men and 10 women had an average age of 49 years, with an average of 3.5 years between stopping and restarting etanercept. Five patients withdrew and were classified as treatment failures, regardless of the reason for withdrawal.
The proportion of responders (defined as those achieving a PGA score of 0 or 1) was 5 of 20 (25%) at week 8, and 8 of 20 (40%) at week 12. Body weight appeared to play a role. Among the 14 patients who had a PGA score of 2 or less at week 12, the average weight was 198.4 pounds, compared with 217.6 pounds for the 6 who did not have that response.
These preliminary findings suggest that rotational therapy is possible, at least in cases of secondary failure with etanercept. Rotational therapy may be possible with other biologics as well, but further studies are necessary, Dr. Kerdel concluded.
It had been thought that this practice would be of limited value because of the development of circulating antibodies, which were found in one study to range in prevalence from 5% of rheumatoid arthritis patients on ustekinumab to 87% of those treated with adalimumab (Clin. Rev. Allergy Immunol. 2010;38:82-9). However, the therapeutic relevance of non-neutralizing vs. neutralizing antibodies is currently unknown, he said.
In a recent prospective cohort study of 272 RA patients treated with adalimumab, 28% had developed antiadalimumab antibodies, which appeared within the first 28 weeks of treatment in two-thirds of them. Over 3 years of follow-up, 38% of the patients with antibodies discontinued adalimumab therapy because of treatment failure, compared with 14% of those who did not develop antibodies. Minimal disease activity was achieved in 48% without antibodies, compared with 13% who had antibodies (JAMA 2011;305:1460-8).
And in a retrospective observational study of 97 psoriasis patients who had been treated with anti–tumor necrosis factor–alpha therapy (60 on a first agent, 22 having failed one agent, 9 having failed two agents, and 6 having failed all three agents), antinuclear antibodies developed in 17%, 54%, 78% and 83%, respectively (Br. J. Dermatol. 2010;162:780-5). "So, antibodies do seem to play a role" in treatment failure, Dr. Kerdel commented.
Dr. Kerdel disclosed that he has been involved in clinical studies, has participated in advisory boards, and is a speaker for Amgen, Abbott, Janssen, Genentech, Astellas, Stiefel, Pfizer, Merck, Novartis, Eisai, and Celgene. SDEF and this news organization are owned by Elsevier.
LAS VEGAS – Emerging data support the practice of switching biologic agents after an initial biologic therapy fails in psoriasis, and even the possibility of rotating back to a biologic that didn’t work previously, according to Dr. Francisco Kerdel, director of the dermatology inpatient service at the University of Miami Hospital.
In one recent series of 747 psoriasis patients on biologics, the 4-year drug response was in the range of 40% for etanercept or adalimumab and 70% for infliximab (Br. J. Dermatol. 2011;164:1091-6). "Thus, there is a logical need for ‘switching’ [biologic] therapy," he noted at the SDEF Las Vegas Dermatology Seminar.
The reasons for treatment failure are not known. Antibody production has been suspected of playing a role, but the presence of antibodies seldom correlates with clinical response, he said.
In a 16-week, open-label trial, a Physician Global Assessment (PGA) rating of "clear" or "minimal" was achieved in 52% of 152 patients who had chronic plaque psoriasis and were switched to adalimumab following suboptimal responses to etanercept, methotrexate, or phototherapy (J. Am. Acad. Dermatol. 2011;64:671-81).
In the PSUNRISE study (a prospective, multicenter, open-label study of infliximab treatment in 215 patients with plaque psoriasis who had had a prior inadequate response to etanercept), a PGA score of 0 (clear) or 1 was achieved by week 10 in 65% of the 179 completers, and 60% remained at PGA 0-1 in weeks 14-26. These data have been submitted for publication, according to Dr. Kerdel, who was one of the study authors.
Good to excellent responses were achieved with ustekinumab at doses of either 45 mg or 90 mg, depending on body weight, in 9 of 11 psoriasis patients who had experienced treatment failures on multiple biologics, including infliximab (11 patients), etanercept (10), efalizumab (9), adalimumab (7), and golimumab (3) (Int. J. Dermatol. 2011;50:478-82).
There is even some evidence that patients can return with success to a biologic therapy that they had previously failed.
Dr. Kerdel and his associates have conducted an open-label study of etanercept re-treatment in 20 patients with moderate to severe psoriasis (defined as a PGA score of 3 or greater) who had had prior therapy with etanercept for a minimum of 6 months but had discontinued it because of loss of efficacy. The 10 men and 10 women had an average age of 49 years, with an average of 3.5 years between stopping and restarting etanercept. Five patients withdrew and were classified as treatment failures, regardless of the reason for withdrawal.
The proportion of responders (defined as those achieving a PGA score of 0 or 1) was 5 of 20 (25%) at week 8, and 8 of 20 (40%) at week 12. Body weight appeared to play a role. Among the 14 patients who had a PGA score of 2 or less at week 12, the average weight was 198.4 pounds, compared with 217.6 pounds for the 6 who did not have that response.
These preliminary findings suggest that rotational therapy is possible, at least in cases of secondary failure with etanercept. Rotational therapy may be possible with other biologics as well, but further studies are necessary, Dr. Kerdel concluded.
It had been thought that this practice would be of limited value because of the development of circulating antibodies, which were found in one study to range in prevalence from 5% of rheumatoid arthritis patients on ustekinumab to 87% of those treated with adalimumab (Clin. Rev. Allergy Immunol. 2010;38:82-9). However, the therapeutic relevance of non-neutralizing vs. neutralizing antibodies is currently unknown, he said.
In a recent prospective cohort study of 272 RA patients treated with adalimumab, 28% had developed antiadalimumab antibodies, which appeared within the first 28 weeks of treatment in two-thirds of them. Over 3 years of follow-up, 38% of the patients with antibodies discontinued adalimumab therapy because of treatment failure, compared with 14% of those who did not develop antibodies. Minimal disease activity was achieved in 48% without antibodies, compared with 13% who had antibodies (JAMA 2011;305:1460-8).
And in a retrospective observational study of 97 psoriasis patients who had been treated with anti–tumor necrosis factor–alpha therapy (60 on a first agent, 22 having failed one agent, 9 having failed two agents, and 6 having failed all three agents), antinuclear antibodies developed in 17%, 54%, 78% and 83%, respectively (Br. J. Dermatol. 2010;162:780-5). "So, antibodies do seem to play a role" in treatment failure, Dr. Kerdel commented.
Dr. Kerdel disclosed that he has been involved in clinical studies, has participated in advisory boards, and is a speaker for Amgen, Abbott, Janssen, Genentech, Astellas, Stiefel, Pfizer, Merck, Novartis, Eisai, and Celgene. SDEF and this news organization are owned by Elsevier.
EXPERT ANALYSIS FROM THE SDEF LAS VEGAS DERMATOLOGY SEMINAR
Laser and Light Devices for Psoriasis, Part 1: Excimer Laser and Phototherapy
For Etanercept Nonresponders, Switch or Escalate?
LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.
During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.
Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.
Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.
The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.
This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.
This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.
LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.
During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.
Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.
Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.
The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.
This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.
This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.
LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.
During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.
Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.
Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.
The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.
This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.
This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Major Finding: During the first 6 months after psoriasis patients were switched from etanercept to adalimumab because of an inadequate response to etanercept, total health care costs averaged $2,451 less than in nonresponders whose etanercept dose was escalated.
Data Source: Analysis of administrative databases containing complete data on health care costs and resource utilization for 728 switchers and 372 dose escalators.
Disclosures: The study was sponsored by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.