Psoriasis Collection

GOTHENBURG, Sweden - A resorbable subcutaneous implant of afamelanotide significantly reduced painful phototoxic attacks in patients with erythropoietic protoporphyria in a year-long multinational clinical trial.

Afamelanotide, a first-in-class investigational chemical analog of alpha-melanocyte-stimulating hormone, is a melanocortin-1 agonist that activates melanocytes and increases melanin levels in the skin.

Treatment with the controlled-release afamelanotide implants was life changing for study participants, Dr. Elisabeth I. Minder noted at the annual congress of the European Academy of Dermatology and Venereology.

Photo: (C) 2009 Lecha et al.; licensee BioMed Central Ltd. (Creative Commons)

"You have to understand that EPP [erythropoietic protoporphyria] patients are conditioned early in life that sunlight is harmful: no exposure to sunlight, no painful attacks. Afamelanotide, compared to placebo, not only reduced phototoxic attacks, it also enabled patients to spend significantly more time outdoors. Anecdotally, patients were quite excited to explore new activities which were never possible in their lives previously," explained Dr. Minder of Triemli Hospital, Zurich.

EPP is a rare inherited disease characterized by severely painful, often intolerable phototoxic attacks lasting for days. An estimated 10,000 individuals are affected worldwide she said.

The afamelanotide implant (Scenesse) is also in clinical trials for more common diseases, including vitiligo, solar urticaria, and polymorphous light eruption, as well as for prevention of actinic keratoses and squamous cell carcinomas in organ transplant recipients.

©Clinuvelt

The European phase III EPP trial involved 100 affected patients who were randomized double blind to a year's worth of alternating treatment cycles consisting of a subcutaneous implant of 16 mg of afamelanotide lasting for 60 days followed by 60 days of a placebo implant.

A total of 91 patients completed the study. The low dropout rate was testimony to how grateful participants were to finally have access to an affective therapy for their disorder, even if for only half of the study period, Dr. Minder said.

Daily pain diaries demonstrated that patients experienced significantly fewer days of severe, moderate, and mild pain during the periods in which they were being treated with afamelanotide. For example, patients spent one-third fewer days in severe pain and less than half as many days in moderate pain during the afamelanotide phase, compared with the placebo phase.

During the active-treatment periods, patients reported spending significantly more time outdoors exposed to the sun. More than half of patients reported spending greater than 6 hours per day outdoors while they were on afamelanotide, something that was unthinkable at baseline.

Only two adverse events were more frequent during active treatment: nausea, which occurred 1-2 days post-implant in 33% of patients when being treated with afamelanotide, compared with 18% of patients when being treated with placebo; and hot flushes, which were noted 1-2 days after afamelanotide implantation in 11% of patients, compared with just 1% with placebo.

Session chair Dr. Maurice Van Steensel of Maastricht (the Netherlands) University commented that a truly double-blind study is impossible with afamelanotide because the alpha-melanocyte-stimulating hormone analog causes tanning. For this very reason, he added, the tanning industry may be interested in this agent as a sunless tanning product.

The U.S. Food and Drug Administration announced in March that Clinuvel (afamelanotide’s manufacturer), could move forward with plans to conduct a phase II clinical trial for treating EPP patients. The confirmatory study is currently enrolling participants. The FDA also granted orphan drug status for the treatment for solar urticaria in late 2009.

In an earlier open-label pilot study, Dr. Minder and her associates showed that treatment with afamelanotide increased tolerance to exposure to artificial light under controlled conditions by 11-fold (N. Engl. J. Med. 2009;360:306-7).

The study was sponsored by Clinuvel Pharmaceuticals. Dr. Minder declared having no financial conflicts.

GOTHENBURG, Sweden - A resorbable subcutaneous implant of afamelanotide significantly reduced painful phototoxic attacks in patients with erythropoietic protoporphyria in a year-long multinational clinical trial.

Afamelanotide, a first-in-class investigational chemical analog of alpha-melanocyte-stimulating hormone, is a melanocortin-1 agonist that activates melanocytes and increases melanin levels in the skin.

Treatment with the controlled-release afamelanotide implants was life changing for study participants, Dr. Elisabeth I. Minder noted at the annual congress of the European Academy of Dermatology and Venereology.

Photo: (C) 2009 Lecha et al.; licensee BioMed Central Ltd. (Creative Commons)

"You have to understand that EPP [erythropoietic protoporphyria] patients are conditioned early in life that sunlight is harmful: no exposure to sunlight, no painful attacks. Afamelanotide, compared to placebo, not only reduced phototoxic attacks, it also enabled patients to spend significantly more time outdoors. Anecdotally, patients were quite excited to explore new activities which were never possible in their lives previously," explained Dr. Minder of Triemli Hospital, Zurich.

EPP is a rare inherited disease characterized by severely painful, often intolerable phototoxic attacks lasting for days. An estimated 10,000 individuals are affected worldwide she said.

The afamelanotide implant (Scenesse) is also in clinical trials for more common diseases, including vitiligo, solar urticaria, and polymorphous light eruption, as well as for prevention of actinic keratoses and squamous cell carcinomas in organ transplant recipients.

©Clinuvelt

The European phase III EPP trial involved 100 affected patients who were randomized double blind to a year's worth of alternating treatment cycles consisting of a subcutaneous implant of 16 mg of afamelanotide lasting for 60 days followed by 60 days of a placebo implant.

A total of 91 patients completed the study. The low dropout rate was testimony to how grateful participants were to finally have access to an affective therapy for their disorder, even if for only half of the study period, Dr. Minder said.

Daily pain diaries demonstrated that patients experienced significantly fewer days of severe, moderate, and mild pain during the periods in which they were being treated with afamelanotide. For example, patients spent one-third fewer days in severe pain and less than half as many days in moderate pain during the afamelanotide phase, compared with the placebo phase.

During the active-treatment periods, patients reported spending significantly more time outdoors exposed to the sun. More than half of patients reported spending greater than 6 hours per day outdoors while they were on afamelanotide, something that was unthinkable at baseline.

Only two adverse events were more frequent during active treatment: nausea, which occurred 1-2 days post-implant in 33% of patients when being treated with afamelanotide, compared with 18% of patients when being treated with placebo; and hot flushes, which were noted 1-2 days after afamelanotide implantation in 11% of patients, compared with just 1% with placebo.

Session chair Dr. Maurice Van Steensel of Maastricht (the Netherlands) University commented that a truly double-blind study is impossible with afamelanotide because the alpha-melanocyte-stimulating hormone analog causes tanning. For this very reason, he added, the tanning industry may be interested in this agent as a sunless tanning product.

The U.S. Food and Drug Administration announced in March that Clinuvel (afamelanotide’s manufacturer), could move forward with plans to conduct a phase II clinical trial for treating EPP patients. The confirmatory study is currently enrolling participants. The FDA also granted orphan drug status for the treatment for solar urticaria in late 2009.

In an earlier open-label pilot study, Dr. Minder and her associates showed that treatment with afamelanotide increased tolerance to exposure to artificial light under controlled conditions by 11-fold (N. Engl. J. Med. 2009;360:306-7).

The study was sponsored by Clinuvel Pharmaceuticals. Dr. Minder declared having no financial conflicts.

GOTHENBURG, Sweden - A resorbable subcutaneous implant of afamelanotide significantly reduced painful phototoxic attacks in patients with erythropoietic protoporphyria in a year-long multinational clinical trial.

Afamelanotide, a first-in-class investigational chemical analog of alpha-melanocyte-stimulating hormone, is a melanocortin-1 agonist that activates melanocytes and increases melanin levels in the skin.

Treatment with the controlled-release afamelanotide implants was life changing for study participants, Dr. Elisabeth I. Minder noted at the annual congress of the European Academy of Dermatology and Venereology.

Photo: (C) 2009 Lecha et al.; licensee BioMed Central Ltd. (Creative Commons)

"You have to understand that EPP [erythropoietic protoporphyria] patients are conditioned early in life that sunlight is harmful: no exposure to sunlight, no painful attacks. Afamelanotide, compared to placebo, not only reduced phototoxic attacks, it also enabled patients to spend significantly more time outdoors. Anecdotally, patients were quite excited to explore new activities which were never possible in their lives previously," explained Dr. Minder of Triemli Hospital, Zurich.

EPP is a rare inherited disease characterized by severely painful, often intolerable phototoxic attacks lasting for days. An estimated 10,000 individuals are affected worldwide she said.

The afamelanotide implant (Scenesse) is also in clinical trials for more common diseases, including vitiligo, solar urticaria, and polymorphous light eruption, as well as for prevention of actinic keratoses and squamous cell carcinomas in organ transplant recipients.

©Clinuvelt

The European phase III EPP trial involved 100 affected patients who were randomized double blind to a year's worth of alternating treatment cycles consisting of a subcutaneous implant of 16 mg of afamelanotide lasting for 60 days followed by 60 days of a placebo implant.

A total of 91 patients completed the study. The low dropout rate was testimony to how grateful participants were to finally have access to an affective therapy for their disorder, even if for only half of the study period, Dr. Minder said.

Daily pain diaries demonstrated that patients experienced significantly fewer days of severe, moderate, and mild pain during the periods in which they were being treated with afamelanotide. For example, patients spent one-third fewer days in severe pain and less than half as many days in moderate pain during the afamelanotide phase, compared with the placebo phase.

During the active-treatment periods, patients reported spending significantly more time outdoors exposed to the sun. More than half of patients reported spending greater than 6 hours per day outdoors while they were on afamelanotide, something that was unthinkable at baseline.

Only two adverse events were more frequent during active treatment: nausea, which occurred 1-2 days post-implant in 33% of patients when being treated with afamelanotide, compared with 18% of patients when being treated with placebo; and hot flushes, which were noted 1-2 days after afamelanotide implantation in 11% of patients, compared with just 1% with placebo.

Session chair Dr. Maurice Van Steensel of Maastricht (the Netherlands) University commented that a truly double-blind study is impossible with afamelanotide because the alpha-melanocyte-stimulating hormone analog causes tanning. For this very reason, he added, the tanning industry may be interested in this agent as a sunless tanning product.

The U.S. Food and Drug Administration announced in March that Clinuvel (afamelanotide’s manufacturer), could move forward with plans to conduct a phase II clinical trial for treating EPP patients. The confirmatory study is currently enrolling participants. The FDA also granted orphan drug status for the treatment for solar urticaria in late 2009.

In an earlier open-label pilot study, Dr. Minder and her associates showed that treatment with afamelanotide increased tolerance to exposure to artificial light under controlled conditions by 11-fold (N. Engl. J. Med. 2009;360:306-7).

The study was sponsored by Clinuvel Pharmaceuticals. Dr. Minder declared having no financial conflicts.

EDINBURGH - Depression is common, underdiagnosed, and undertreated in patients with psoriatic arthritis.

Psychiatric evaluation of 50 consecutive patients at the University of Glasgow psoriatic arthritis clinic indicated that 15 patients, or 30%, were depressed. Three were rated as severely depressed based on their scores on the Hospital Anxiety and Depression Scale (HADS), while 12 others had moderate depression, Dr. Rajeev Krishnadas reported at the International Congress of the Royal College of Psychiatrists.

This high prevalence of depression in psoriatic arthritis patients is consistent with reports in the dermatologic literature (Br. J. Dermatol. 2008;159:704-10).

Of note, none of the depressed Scottish psoriatic arthritis patients was on a therapeutic dose of an antidepressant, added Dr. Krishnadas of the Sackler Institute of Psychobiological Research, Southern General Hospital, Glasgow.

This study is part of a larger ongoing investigation looking at the relationship between systemic inflammation and depression in patients with rheumatoid arthritis or psoriatic arthritis. In this portion of the study, a positive association was noted between HADS scores and C-reactive protein levels in the psoriatic arthritis cohort, although it must be noted that CRP scores accounted for only 7% of the overall variance in HADS scores.

Not surprisingly, higher HADS scores were associated with worse quality of life as assessed by the Dermatology Quality of Life Questionnaire as well as with higher scores on a self-rated pain scale.

Of greater interest psychodynamically, a negative correlation was found between HADS scores and emotional intelligence as measured by the Trait Emotional Intelligence Questionnaire – Short Form. High trait emotional intelligence reflects greater awareness of one's own feelings as well as the feelings of others'. Individuals with high emotional intelligence are far better able to regulate their emotions than are those with lower trait emotional intelligence.

Patients who scored high in trait emotional intelligence had higher quality of life scores, lower CRP levels, and lower scores on the pain scale.

These findings are consistent with the hypothesis that a poor ability to be aware of and regulate one's emotions predisposes to depression in the presence of a chronic medical condition or other major stressor, according to Dr. Krishnadas.

He declared having no conflicts of interest.

EDINBURGH - Depression is common, underdiagnosed, and undertreated in patients with psoriatic arthritis.

Psychiatric evaluation of 50 consecutive patients at the University of Glasgow psoriatic arthritis clinic indicated that 15 patients, or 30%, were depressed. Three were rated as severely depressed based on their scores on the Hospital Anxiety and Depression Scale (HADS), while 12 others had moderate depression, Dr. Rajeev Krishnadas reported at the International Congress of the Royal College of Psychiatrists.

This high prevalence of depression in psoriatic arthritis patients is consistent with reports in the dermatologic literature (Br. J. Dermatol. 2008;159:704-10).

Of note, none of the depressed Scottish psoriatic arthritis patients was on a therapeutic dose of an antidepressant, added Dr. Krishnadas of the Sackler Institute of Psychobiological Research, Southern General Hospital, Glasgow.

This study is part of a larger ongoing investigation looking at the relationship between systemic inflammation and depression in patients with rheumatoid arthritis or psoriatic arthritis. In this portion of the study, a positive association was noted between HADS scores and C-reactive protein levels in the psoriatic arthritis cohort, although it must be noted that CRP scores accounted for only 7% of the overall variance in HADS scores.

Not surprisingly, higher HADS scores were associated with worse quality of life as assessed by the Dermatology Quality of Life Questionnaire as well as with higher scores on a self-rated pain scale.

Of greater interest psychodynamically, a negative correlation was found between HADS scores and emotional intelligence as measured by the Trait Emotional Intelligence Questionnaire – Short Form. High trait emotional intelligence reflects greater awareness of one's own feelings as well as the feelings of others'. Individuals with high emotional intelligence are far better able to regulate their emotions than are those with lower trait emotional intelligence.

Patients who scored high in trait emotional intelligence had higher quality of life scores, lower CRP levels, and lower scores on the pain scale.

These findings are consistent with the hypothesis that a poor ability to be aware of and regulate one's emotions predisposes to depression in the presence of a chronic medical condition or other major stressor, according to Dr. Krishnadas.

He declared having no conflicts of interest.

EDINBURGH - Depression is common, underdiagnosed, and undertreated in patients with psoriatic arthritis.

Psychiatric evaluation of 50 consecutive patients at the University of Glasgow psoriatic arthritis clinic indicated that 15 patients, or 30%, were depressed. Three were rated as severely depressed based on their scores on the Hospital Anxiety and Depression Scale (HADS), while 12 others had moderate depression, Dr. Rajeev Krishnadas reported at the International Congress of the Royal College of Psychiatrists.

This high prevalence of depression in psoriatic arthritis patients is consistent with reports in the dermatologic literature (Br. J. Dermatol. 2008;159:704-10).

Of note, none of the depressed Scottish psoriatic arthritis patients was on a therapeutic dose of an antidepressant, added Dr. Krishnadas of the Sackler Institute of Psychobiological Research, Southern General Hospital, Glasgow.

This study is part of a larger ongoing investigation looking at the relationship between systemic inflammation and depression in patients with rheumatoid arthritis or psoriatic arthritis. In this portion of the study, a positive association was noted between HADS scores and C-reactive protein levels in the psoriatic arthritis cohort, although it must be noted that CRP scores accounted for only 7% of the overall variance in HADS scores.

Not surprisingly, higher HADS scores were associated with worse quality of life as assessed by the Dermatology Quality of Life Questionnaire as well as with higher scores on a self-rated pain scale.

Of greater interest psychodynamically, a negative correlation was found between HADS scores and emotional intelligence as measured by the Trait Emotional Intelligence Questionnaire – Short Form. High trait emotional intelligence reflects greater awareness of one's own feelings as well as the feelings of others'. Individuals with high emotional intelligence are far better able to regulate their emotions than are those with lower trait emotional intelligence.

Patients who scored high in trait emotional intelligence had higher quality of life scores, lower CRP levels, and lower scores on the pain scale.

These findings are consistent with the hypothesis that a poor ability to be aware of and regulate one's emotions predisposes to depression in the presence of a chronic medical condition or other major stressor, according to Dr. Krishnadas.

He declared having no conflicts of interest.

GOTHENBURG, Sweden – Rapid progression of cutaneous lupus erythematosus to SLE occurs considerably more often than previously recognized, a comprehensive nationwide Swedish study found.

The population-based study, which included all 1,088 patients diagnosed with CLE in Sweden from 2005 to 2007, found that the risk of being diagnosed with SLE during the first year of CLE diagnosis was 12%. The 3-year rate of progression to SLE was 18%, Dr. Carina M. Grönhagen reported at the annual congress of the European Academy of Dermatology and Venereology.

Moreover, 24% of patients already carried the diagnosis of SLE at the time they were diagnosed with CLE, added Dr. Grönhagen, a dermatology resident at the Karolinska Institutet, Danderyd Hospital, Stockholm.

Patients with the subacute form of CLE had the highest rate of early progression to SLE, with a 3-year incidence of nearly 25%. Patients with subacute CLE accounted for 15.7% of the overall Swedish CLE cohort.

Discoid CLE accounted for 79.8% of all cases of CLE diagnosed in Sweden during the study period, while lupus panniculitis and other less common forms of local LE comprised the remainder.

Women with newly diagnosed CLE had a 3-year rate of progression to SLE of 20%, twice that of men. The incidence of CLE was threefold greater in Swedish women than men.

Patients with newly diagnosed CLE should be informed of the risk of early progression to SLE, Dr. Grönhagen said. They should be made aware of the systemic signs and symptoms, such as fevers and joint pains, so appropriate treatment for SLE is not delayed.

Her study relied upon Swedish National Patient Register data, which, since 2001, has included outpatient specialist care as well as inpatient care.

The incidence of CLE in Sweden, based on these data, is 4.0 per 100,000 population per year. The peak incidence of CLE in women was in the 65- to 74-year-old group, while the peak in men was at age 55-64. This pattern was skewed in the subset of patients with subacute CLE; their peak incidence was later, and there were far fewer cases diagnosed before age 45 than for discoid and other forms of CLE.

"One theory behind this is that the subacute form is drug induced to a larger extent than previously believed. An important known trigger for subacute CLE is antihypertensive drugs, which are mostly taken by people age 45 and older," Dr. Grönhagen said.

During her presentation at the meeting of the European Society of Cutaneous Lupus Erythematosus, held in conjunction with the EADV congress, audience members noted that there has been a dearth of population-based studies reporting the incidence of isolated CLE. They also commented on the large size of the population in Dr. Grönhagen’s study and the 3-year follow-up.

Audience members noted that the Swedish national study, since it included outpatients as well as inpatients, is relatively immune to selection bias. Although it was noted that the reported CLE incidence of 4.0/100,000 is up to 10-fold lower than cited in some other studies, Dr. Grönhagen countered that prior studies have been much smaller and less comprehensive.

Still, she said, the 4.0/100,000 incidence figure is probably an underestimate. It is likely that the mildest cases of discoid LE were never referred to a dermatologist or other specialist and, hence, weren't recorded in the outpatient portion of the national registry.

Dr. Grönhagen declared having no relevant financial interests.

GOTHENBURG, Sweden – Rapid progression of cutaneous lupus erythematosus to SLE occurs considerably more often than previously recognized, a comprehensive nationwide Swedish study found.

The population-based study, which included all 1,088 patients diagnosed with CLE in Sweden from 2005 to 2007, found that the risk of being diagnosed with SLE during the first year of CLE diagnosis was 12%. The 3-year rate of progression to SLE was 18%, Dr. Carina M. Grönhagen reported at the annual congress of the European Academy of Dermatology and Venereology.

Moreover, 24% of patients already carried the diagnosis of SLE at the time they were diagnosed with CLE, added Dr. Grönhagen, a dermatology resident at the Karolinska Institutet, Danderyd Hospital, Stockholm.

Patients with the subacute form of CLE had the highest rate of early progression to SLE, with a 3-year incidence of nearly 25%. Patients with subacute CLE accounted for 15.7% of the overall Swedish CLE cohort.

Discoid CLE accounted for 79.8% of all cases of CLE diagnosed in Sweden during the study period, while lupus panniculitis and other less common forms of local LE comprised the remainder.

Women with newly diagnosed CLE had a 3-year rate of progression to SLE of 20%, twice that of men. The incidence of CLE was threefold greater in Swedish women than men.

Patients with newly diagnosed CLE should be informed of the risk of early progression to SLE, Dr. Grönhagen said. They should be made aware of the systemic signs and symptoms, such as fevers and joint pains, so appropriate treatment for SLE is not delayed.

Her study relied upon Swedish National Patient Register data, which, since 2001, has included outpatient specialist care as well as inpatient care.

The incidence of CLE in Sweden, based on these data, is 4.0 per 100,000 population per year. The peak incidence of CLE in women was in the 65- to 74-year-old group, while the peak in men was at age 55-64. This pattern was skewed in the subset of patients with subacute CLE; their peak incidence was later, and there were far fewer cases diagnosed before age 45 than for discoid and other forms of CLE.

"One theory behind this is that the subacute form is drug induced to a larger extent than previously believed. An important known trigger for subacute CLE is antihypertensive drugs, which are mostly taken by people age 45 and older," Dr. Grönhagen said.

During her presentation at the meeting of the European Society of Cutaneous Lupus Erythematosus, held in conjunction with the EADV congress, audience members noted that there has been a dearth of population-based studies reporting the incidence of isolated CLE. They also commented on the large size of the population in Dr. Grönhagen’s study and the 3-year follow-up.

Audience members noted that the Swedish national study, since it included outpatients as well as inpatients, is relatively immune to selection bias. Although it was noted that the reported CLE incidence of 4.0/100,000 is up to 10-fold lower than cited in some other studies, Dr. Grönhagen countered that prior studies have been much smaller and less comprehensive.

Still, she said, the 4.0/100,000 incidence figure is probably an underestimate. It is likely that the mildest cases of discoid LE were never referred to a dermatologist or other specialist and, hence, weren't recorded in the outpatient portion of the national registry.

Dr. Grönhagen declared having no relevant financial interests.

GOTHENBURG, Sweden – Rapid progression of cutaneous lupus erythematosus to SLE occurs considerably more often than previously recognized, a comprehensive nationwide Swedish study found.

The population-based study, which included all 1,088 patients diagnosed with CLE in Sweden from 2005 to 2007, found that the risk of being diagnosed with SLE during the first year of CLE diagnosis was 12%. The 3-year rate of progression to SLE was 18%, Dr. Carina M. Grönhagen reported at the annual congress of the European Academy of Dermatology and Venereology.

Moreover, 24% of patients already carried the diagnosis of SLE at the time they were diagnosed with CLE, added Dr. Grönhagen, a dermatology resident at the Karolinska Institutet, Danderyd Hospital, Stockholm.

Patients with the subacute form of CLE had the highest rate of early progression to SLE, with a 3-year incidence of nearly 25%. Patients with subacute CLE accounted for 15.7% of the overall Swedish CLE cohort.

Discoid CLE accounted for 79.8% of all cases of CLE diagnosed in Sweden during the study period, while lupus panniculitis and other less common forms of local LE comprised the remainder.

Women with newly diagnosed CLE had a 3-year rate of progression to SLE of 20%, twice that of men. The incidence of CLE was threefold greater in Swedish women than men.

Patients with newly diagnosed CLE should be informed of the risk of early progression to SLE, Dr. Grönhagen said. They should be made aware of the systemic signs and symptoms, such as fevers and joint pains, so appropriate treatment for SLE is not delayed.

Her study relied upon Swedish National Patient Register data, which, since 2001, has included outpatient specialist care as well as inpatient care.

The incidence of CLE in Sweden, based on these data, is 4.0 per 100,000 population per year. The peak incidence of CLE in women was in the 65- to 74-year-old group, while the peak in men was at age 55-64. This pattern was skewed in the subset of patients with subacute CLE; their peak incidence was later, and there were far fewer cases diagnosed before age 45 than for discoid and other forms of CLE.

"One theory behind this is that the subacute form is drug induced to a larger extent than previously believed. An important known trigger for subacute CLE is antihypertensive drugs, which are mostly taken by people age 45 and older," Dr. Grönhagen said.

During her presentation at the meeting of the European Society of Cutaneous Lupus Erythematosus, held in conjunction with the EADV congress, audience members noted that there has been a dearth of population-based studies reporting the incidence of isolated CLE. They also commented on the large size of the population in Dr. Grönhagen’s study and the 3-year follow-up.

Audience members noted that the Swedish national study, since it included outpatients as well as inpatients, is relatively immune to selection bias. Although it was noted that the reported CLE incidence of 4.0/100,000 is up to 10-fold lower than cited in some other studies, Dr. Grönhagen countered that prior studies have been much smaller and less comprehensive.

Still, she said, the 4.0/100,000 incidence figure is probably an underestimate. It is likely that the mildest cases of discoid LE were never referred to a dermatologist or other specialist and, hence, weren't recorded in the outpatient portion of the national registry.

Dr. Grönhagen declared having no relevant financial interests.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three – adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs £9,295 ($14,782.50) per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs £9,295 ($14,782.50) per year, assuming a 40-mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs £10,910 ($17,352.16) per year based on infusions repeated every 8 weeks (average of 6.5 doses per year), according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated £9,295 (14,782.50) per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a "significant" portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug's monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum. 2009;60:976-86). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, "the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment," and in the case of an adverse event, "it would take longer for the treatment effect to wear off."

NICE's guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three – adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs £9,295 ($14,782.50) per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs £9,295 ($14,782.50) per year, assuming a 40-mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs £10,910 ($17,352.16) per year based on infusions repeated every 8 weeks (average of 6.5 doses per year), according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated £9,295 (14,782.50) per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a "significant" portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug's monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum. 2009;60:976-86). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, "the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment," and in the case of an adverse event, "it would take longer for the treatment effect to wear off."

NICE's guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three – adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs £9,295 ($14,782.50) per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs £9,295 ($14,782.50) per year, assuming a 40-mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs £10,910 ($17,352.16) per year based on infusions repeated every 8 weeks (average of 6.5 doses per year), according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated £9,295 (14,782.50) per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a "significant" portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug's monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum. 2009;60:976-86). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, "the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment," and in the case of an adverse event, "it would take longer for the treatment effect to wear off."

NICE's guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

Companies that manufacture, distribute, and/or market unapproved formulations of the oral, single ingredient forms of the gout drug colchicine have been ordered to stop doing so, the Food and Drug Administration announced on Sept. 30.

The companies must stop manufacturing these products within 45 days of the announcement and stop shipping unapproved colchicine within 90 days of the announcement, according to the statement, which says that a small amount of unapproved colchicine will be available after these dates, until supplies are used up.

Oral colchicine products are among the drugs that have been on the market for so many years that they were never subjected to the current prescription drug approval process. The FDA has launched an initiative to target the manufacturers of colchicine and other older, unapproved drugs to conduct the necessary testing to meet current approval standards or take them off the market.

Once the older products are off the market, the only oral colchicine product that will be available is Colcrys, marketed by Mutual Pharmaceuticals/URL Pharma, which was approved in 2009, after the company met the current drug approval requirements. As a result, the drug’s label includes information on safety data, drug interactions, and dosing that is not available for the older unapproved versions, according to the FDA.

The FDA's approval of Colcrys and the plans to ban the marketing of the older products has been sharply criticized by some clinicians who treat patients with gout because Colcrys is significantly more expensive than the older, unapproved formulations.

The FDA statement notes that the manufacturer of Colcrys has established a patient assistance program for patients who can’t afford the brand-name drug and those on Medicare who don’t want the cost of the drug to contribute to their out-of-pocket Medicare Part D expenses. More information about that program is available at the Colcrys Web site or at Needy Meds, an umbrella organization that offers patient assistance, or by calling 888-811-8423. The company has said that the program will continue "at a minimum until there is FDA-approved generic competition" for Colcrys, according to the statement.

The agency is encouraging manufacturers of such products to pursue approval of their products or "to face the type of action announced today," Deborah Autor, director of the office of compliance at the FDA's Center for Drug Evaluation and Research (CDER), said in the statement.

The FDA ordered a halt to unapproved colchicine for injection products in 2008.

Companies that manufacture, distribute, and/or market unapproved formulations of the oral, single ingredient forms of the gout drug colchicine have been ordered to stop doing so, the Food and Drug Administration announced on Sept. 30.

The companies must stop manufacturing these products within 45 days of the announcement and stop shipping unapproved colchicine within 90 days of the announcement, according to the statement, which says that a small amount of unapproved colchicine will be available after these dates, until supplies are used up.

Oral colchicine products are among the drugs that have been on the market for so many years that they were never subjected to the current prescription drug approval process. The FDA has launched an initiative to target the manufacturers of colchicine and other older, unapproved drugs to conduct the necessary testing to meet current approval standards or take them off the market.

Once the older products are off the market, the only oral colchicine product that will be available is Colcrys, marketed by Mutual Pharmaceuticals/URL Pharma, which was approved in 2009, after the company met the current drug approval requirements. As a result, the drug’s label includes information on safety data, drug interactions, and dosing that is not available for the older unapproved versions, according to the FDA.

The FDA's approval of Colcrys and the plans to ban the marketing of the older products has been sharply criticized by some clinicians who treat patients with gout because Colcrys is significantly more expensive than the older, unapproved formulations.

The FDA statement notes that the manufacturer of Colcrys has established a patient assistance program for patients who can’t afford the brand-name drug and those on Medicare who don’t want the cost of the drug to contribute to their out-of-pocket Medicare Part D expenses. More information about that program is available at the Colcrys Web site or at Needy Meds, an umbrella organization that offers patient assistance, or by calling 888-811-8423. The company has said that the program will continue "at a minimum until there is FDA-approved generic competition" for Colcrys, according to the statement.

The agency is encouraging manufacturers of such products to pursue approval of their products or "to face the type of action announced today," Deborah Autor, director of the office of compliance at the FDA's Center for Drug Evaluation and Research (CDER), said in the statement.

The FDA ordered a halt to unapproved colchicine for injection products in 2008.

Companies that manufacture, distribute, and/or market unapproved formulations of the oral, single ingredient forms of the gout drug colchicine have been ordered to stop doing so, the Food and Drug Administration announced on Sept. 30.

The companies must stop manufacturing these products within 45 days of the announcement and stop shipping unapproved colchicine within 90 days of the announcement, according to the statement, which says that a small amount of unapproved colchicine will be available after these dates, until supplies are used up.

Oral colchicine products are among the drugs that have been on the market for so many years that they were never subjected to the current prescription drug approval process. The FDA has launched an initiative to target the manufacturers of colchicine and other older, unapproved drugs to conduct the necessary testing to meet current approval standards or take them off the market.

Once the older products are off the market, the only oral colchicine product that will be available is Colcrys, marketed by Mutual Pharmaceuticals/URL Pharma, which was approved in 2009, after the company met the current drug approval requirements. As a result, the drug’s label includes information on safety data, drug interactions, and dosing that is not available for the older unapproved versions, according to the FDA.

The FDA's approval of Colcrys and the plans to ban the marketing of the older products has been sharply criticized by some clinicians who treat patients with gout because Colcrys is significantly more expensive than the older, unapproved formulations.

The FDA statement notes that the manufacturer of Colcrys has established a patient assistance program for patients who can’t afford the brand-name drug and those on Medicare who don’t want the cost of the drug to contribute to their out-of-pocket Medicare Part D expenses. More information about that program is available at the Colcrys Web site or at Needy Meds, an umbrella organization that offers patient assistance, or by calling 888-811-8423. The company has said that the program will continue "at a minimum until there is FDA-approved generic competition" for Colcrys, according to the statement.

The agency is encouraging manufacturers of such products to pursue approval of their products or "to face the type of action announced today," Deborah Autor, director of the office of compliance at the FDA's Center for Drug Evaluation and Research (CDER), said in the statement.

The FDA ordered a halt to unapproved colchicine for injection products in 2008.

SAN FRANCISCO – It falls into a dermatologist's realm of responsibility to help women with psoriasis overcome treatment barriers and improve their psychosocial well-being, according to Dr. Jennifer C. Cather.

Women often are the main caregivers for their families and thus may put their family's health care needs before their own, Dr. Cather noted at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation. Dermatologists should stress to these patients the importance of making their medical needs a priority.

"I see many women who have gone untreated or undertreated for many years despite being under the care of a dermatologist, or even several other dermatologists, before arriving in our office. It is important for women to make their own health a priority and then to seek out a dermatologist with whom they can frankly discuss the range of therapeutic options and their correlating implications," Dr. Cather said in an interview.

"The reality is that, however complicated it is to treat psoriasis, the complications of not treating the disease can often be much worse," said Dr. Cather, medical director at Modern Dermatology and Modern Research Associates, Dallas.

Although the prevalence of psoriasis is approximately the same by gender, the condition has a greater psychosocial impact on women than on men, multiple surveys have indicated. For example, 20% of women vs. 12% of men reported their psoriasis was a "very large problem in their everyday lives," the National Psoriasis Foundation discovered when they asked 4,725 people from 2004 to 2009 ("Report on the Psycho-Social Impacts of Psoriasis").

In addition, women reported a higher symptom burden than did men. Women were 17% more likely to report itching; 16% more likely to report physical irritation; and 24% more likely to report pain associated with their psoriasis, compared with men, according to the online report.

Other researchers discovered a statistically significant reduction in quality of life for women with psoriasis versus men, based on a survey of 266 psoriasis patients (J. Am. Acad. Dermatol. 2004:51:704-8).

"Wearing a chronic disease on the outside of your body is a real struggle in a society as focused on appearance as ours is," Dr. Cather said. The average age of psoriasis onset is between 15 and 35 years, a time when many women are making important choices about their future. The impact of low self-esteem associated with this condition can have far reaching implications.

Therefore, it is important for dermatologists to take the time to assess the patient's well-being. In addition to measurement of affected body surface area, inflammatory burden, joint involvement, and other medical issues using validated instruments, ask women some simple questions, Dr. Cather said. Examples include: "How is your psoriasis today?" and "Is the cost of your therapy worth it?"

"We need to understand how each patient is experiencing the disease and whether he or she is satisfied with the treatment option we have selected," Dr. Cather said. "Satisfied patients are compliant with the treatment regimen and have a greater chance of success over the long term."

Photo courtesy Dr. Jennifer C. Cather

The good news is that systemic medication can make a big difference in the lives of women affected by psoriasis. Tumor necrosis factor (TNF) antagonists are the treatment of choice for Dr. Cather when patients present with psoriasis and psoriatic arthritis. These agents can have a synergistic benefit when given with methotrexate, she said.

Interestingly, women with higher body mass index tend to respond better to monoclonal antibody treatments, Dr. Cather said. Also, keep in mind that psoriasis treatment needs may change for a particular woman throughout her life.

Photo courtesy Dr. Jennifer C. Cather

Dr. Cather presented several cases of women who responded well to systemic therapy. These included a young teenage girl whose plaques cleared following treatment with etanercept; and an older teenage girl – treated previously with adalimumab, efalizumab, and cyclosporine A – who responded to two injections of ustekinumab 45 mg. She also presented the case of a 55-year-old woman previously prescribed methotrexate and etanercept. The patient’s subsequent treatment with adalimumab has been "life changing"; her psoriasis has been clear since 2003.

Begin with a thorough physical examination, including a total body skin evaluation, and medical history, Dr. Cather said. Physical exam also can include a Pap smear, mammogram, and colonoscopy. Ask women about their history of malignancy, infections, and vaccinations. Inquire about their social history as well, she recommended.

A complete blood count, comprehensive metabolic panel, and high-sensitivity C-reaction protein assay are recommended laboratory tests. A screen for hepatitis B and C, HIV infection, and tuberculosis (repeated annually) can be helpful in the differential diagnosis.

In terms of future research, Dr. Cather said:"In our clinic, we are currently exploring the incorporation of more formal validated quality-of-life measures to dig deeper into how psoriasis is impacting life decisions and productivity."

Disclosures: Dr. Cather disclosed that she is a consultant for and on the speaker’s bureau of Abbott Laboratories and Centocor Inc. She also is a researcher for Amgen, Celgene Corp., and Pfizer.

SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – It falls into a dermatologist's realm of responsibility to help women with psoriasis overcome treatment barriers and improve their psychosocial well-being, according to Dr. Jennifer C. Cather.

Women often are the main caregivers for their families and thus may put their family's health care needs before their own, Dr. Cather noted at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation. Dermatologists should stress to these patients the importance of making their medical needs a priority.

"I see many women who have gone untreated or undertreated for many years despite being under the care of a dermatologist, or even several other dermatologists, before arriving in our office. It is important for women to make their own health a priority and then to seek out a dermatologist with whom they can frankly discuss the range of therapeutic options and their correlating implications," Dr. Cather said in an interview.

"The reality is that, however complicated it is to treat psoriasis, the complications of not treating the disease can often be much worse," said Dr. Cather, medical director at Modern Dermatology and Modern Research Associates, Dallas.

Although the prevalence of psoriasis is approximately the same by gender, the condition has a greater psychosocial impact on women than on men, multiple surveys have indicated. For example, 20% of women vs. 12% of men reported their psoriasis was a "very large problem in their everyday lives," the National Psoriasis Foundation discovered when they asked 4,725 people from 2004 to 2009 ("Report on the Psycho-Social Impacts of Psoriasis").

In addition, women reported a higher symptom burden than did men. Women were 17% more likely to report itching; 16% more likely to report physical irritation; and 24% more likely to report pain associated with their psoriasis, compared with men, according to the online report.

Other researchers discovered a statistically significant reduction in quality of life for women with psoriasis versus men, based on a survey of 266 psoriasis patients (J. Am. Acad. Dermatol. 2004:51:704-8).

"Wearing a chronic disease on the outside of your body is a real struggle in a society as focused on appearance as ours is," Dr. Cather said. The average age of psoriasis onset is between 15 and 35 years, a time when many women are making important choices about their future. The impact of low self-esteem associated with this condition can have far reaching implications.

Therefore, it is important for dermatologists to take the time to assess the patient's well-being. In addition to measurement of affected body surface area, inflammatory burden, joint involvement, and other medical issues using validated instruments, ask women some simple questions, Dr. Cather said. Examples include: "How is your psoriasis today?" and "Is the cost of your therapy worth it?"

"We need to understand how each patient is experiencing the disease and whether he or she is satisfied with the treatment option we have selected," Dr. Cather said. "Satisfied patients are compliant with the treatment regimen and have a greater chance of success over the long term."

Photo courtesy Dr. Jennifer C. Cather

The good news is that systemic medication can make a big difference in the lives of women affected by psoriasis. Tumor necrosis factor (TNF) antagonists are the treatment of choice for Dr. Cather when patients present with psoriasis and psoriatic arthritis. These agents can have a synergistic benefit when given with methotrexate, she said.

Interestingly, women with higher body mass index tend to respond better to monoclonal antibody treatments, Dr. Cather said. Also, keep in mind that psoriasis treatment needs may change for a particular woman throughout her life.

Photo courtesy Dr. Jennifer C. Cather

Dr. Cather presented several cases of women who responded well to systemic therapy. These included a young teenage girl whose plaques cleared following treatment with etanercept; and an older teenage girl – treated previously with adalimumab, efalizumab, and cyclosporine A – who responded to two injections of ustekinumab 45 mg. She also presented the case of a 55-year-old woman previously prescribed methotrexate and etanercept. The patient’s subsequent treatment with adalimumab has been "life changing"; her psoriasis has been clear since 2003.

Begin with a thorough physical examination, including a total body skin evaluation, and medical history, Dr. Cather said. Physical exam also can include a Pap smear, mammogram, and colonoscopy. Ask women about their history of malignancy, infections, and vaccinations. Inquire about their social history as well, she recommended.

A complete blood count, comprehensive metabolic panel, and high-sensitivity C-reaction protein assay are recommended laboratory tests. A screen for hepatitis B and C, HIV infection, and tuberculosis (repeated annually) can be helpful in the differential diagnosis.

In terms of future research, Dr. Cather said:"In our clinic, we are currently exploring the incorporation of more formal validated quality-of-life measures to dig deeper into how psoriasis is impacting life decisions and productivity."

Disclosures: Dr. Cather disclosed that she is a consultant for and on the speaker’s bureau of Abbott Laboratories and Centocor Inc. She also is a researcher for Amgen, Celgene Corp., and Pfizer.

SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – It falls into a dermatologist's realm of responsibility to help women with psoriasis overcome treatment barriers and improve their psychosocial well-being, according to Dr. Jennifer C. Cather.

Women often are the main caregivers for their families and thus may put their family's health care needs before their own, Dr. Cather noted at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation. Dermatologists should stress to these patients the importance of making their medical needs a priority.

"I see many women who have gone untreated or undertreated for many years despite being under the care of a dermatologist, or even several other dermatologists, before arriving in our office. It is important for women to make their own health a priority and then to seek out a dermatologist with whom they can frankly discuss the range of therapeutic options and their correlating implications," Dr. Cather said in an interview.

"The reality is that, however complicated it is to treat psoriasis, the complications of not treating the disease can often be much worse," said Dr. Cather, medical director at Modern Dermatology and Modern Research Associates, Dallas.

Although the prevalence of psoriasis is approximately the same by gender, the condition has a greater psychosocial impact on women than on men, multiple surveys have indicated. For example, 20% of women vs. 12% of men reported their psoriasis was a "very large problem in their everyday lives," the National Psoriasis Foundation discovered when they asked 4,725 people from 2004 to 2009 ("Report on the Psycho-Social Impacts of Psoriasis").

In addition, women reported a higher symptom burden than did men. Women were 17% more likely to report itching; 16% more likely to report physical irritation; and 24% more likely to report pain associated with their psoriasis, compared with men, according to the online report.

Other researchers discovered a statistically significant reduction in quality of life for women with psoriasis versus men, based on a survey of 266 psoriasis patients (J. Am. Acad. Dermatol. 2004:51:704-8).

"Wearing a chronic disease on the outside of your body is a real struggle in a society as focused on appearance as ours is," Dr. Cather said. The average age of psoriasis onset is between 15 and 35 years, a time when many women are making important choices about their future. The impact of low self-esteem associated with this condition can have far reaching implications.

Therefore, it is important for dermatologists to take the time to assess the patient's well-being. In addition to measurement of affected body surface area, inflammatory burden, joint involvement, and other medical issues using validated instruments, ask women some simple questions, Dr. Cather said. Examples include: "How is your psoriasis today?" and "Is the cost of your therapy worth it?"

"We need to understand how each patient is experiencing the disease and whether he or she is satisfied with the treatment option we have selected," Dr. Cather said. "Satisfied patients are compliant with the treatment regimen and have a greater chance of success over the long term."

Photo courtesy Dr. Jennifer C. Cather

The good news is that systemic medication can make a big difference in the lives of women affected by psoriasis. Tumor necrosis factor (TNF) antagonists are the treatment of choice for Dr. Cather when patients present with psoriasis and psoriatic arthritis. These agents can have a synergistic benefit when given with methotrexate, she said.

Interestingly, women with higher body mass index tend to respond better to monoclonal antibody treatments, Dr. Cather said. Also, keep in mind that psoriasis treatment needs may change for a particular woman throughout her life.

Photo courtesy Dr. Jennifer C. Cather

Dr. Cather presented several cases of women who responded well to systemic therapy. These included a young teenage girl whose plaques cleared following treatment with etanercept; and an older teenage girl – treated previously with adalimumab, efalizumab, and cyclosporine A – who responded to two injections of ustekinumab 45 mg. She also presented the case of a 55-year-old woman previously prescribed methotrexate and etanercept. The patient’s subsequent treatment with adalimumab has been "life changing"; her psoriasis has been clear since 2003.

Begin with a thorough physical examination, including a total body skin evaluation, and medical history, Dr. Cather said. Physical exam also can include a Pap smear, mammogram, and colonoscopy. Ask women about their history of malignancy, infections, and vaccinations. Inquire about their social history as well, she recommended.

A complete blood count, comprehensive metabolic panel, and high-sensitivity C-reaction protein assay are recommended laboratory tests. A screen for hepatitis B and C, HIV infection, and tuberculosis (repeated annually) can be helpful in the differential diagnosis.

In terms of future research, Dr. Cather said:"In our clinic, we are currently exploring the incorporation of more formal validated quality-of-life measures to dig deeper into how psoriasis is impacting life decisions and productivity."

Disclosures: Dr. Cather disclosed that she is a consultant for and on the speaker’s bureau of Abbott Laboratories and Centocor Inc. She also is a researcher for Amgen, Celgene Corp., and Pfizer.

SDEF and this news organization are owned by Elsevier.

Rheumatic disease patients who are exposed to tumor necrosis factor antagonists have a 10-fold increased risk of hospitalization for varicella zoster virus infections, compared with the general population, according to a secondary analysis of two large databases.

Nonetheless, the absolute incidence of varicella-related hospitalizations remains low at about three cases per 10,000 person-years of exposure, and the risks of using vaccination for prevention likely outweigh the benefits, Dr. Ignacio Garcia-Doval of Complexo Hospitalario de Pontevedra (Spain) and colleagues have reported in the October issue of the Annals of the Rheumatic Diseases.

The estimated incidence rate of hospitalization for shingles in the rheumatic population was 32 cases per 100,000 patient years, compared with an expected rate of 3.4 in the general population, and the estimated incidence of hospitalization for chickenpox in the rheumatic patients was 26 per 100,000, compared with 1.9 in the general population. This finding is based on analysis of data from a national registry of rheumatic disease patients who were treated with TNF agents (BIOBADASER database) and from an administrative database of all hospital admissions in public centers in Spain (Conjunto Mínimo Básico de Datos al Alta Hospitalaria, or CMBD), which together represent more than 114 million patient-years.

The estimated age- and sex-standardized incidence rate per 100,000 person-years, and the estimated standardized incidence difference were 9 and 26, respectively, for shingles, and 19 and 33, respectively, for chickenpox, they said (Ann. Rheum. Dis. 2010;69:1751-5).

TNF antagonists are known to be associated with an increased risk of tuberculosis in particular and of opportunistic infections in general. There is a biological basis for an increased risk of viral infections, the investigators said, noting that although some studies have shown an increased rate of viral infection in TNF antagonist–treated patients, the clinical relevance of the increase is uncertain.

The current study does not allow differentiation of the causes for the increased risk, but it does show that the absolute rate is low.

The investigators said it is unlikely that the cohorts received systematic vaccination against varicella zoster virus, since the general health mandate in Spain was given in 2005 and only for children aged 11-14 years.

"Standard guidelines for chickenpox vaccination probably apply to the population included in our study," they wrote.

However, shingles vaccine, which is an attenuated vaccine with a higher dose of antigen, could potentially lead to more side effects in an immunosuppressed population, they said.

For example, in a randomized trial of adults older than age 60 years, shingles vaccine was associated with 7 cases of severe adverse events and 14 cases of vaccine-related adverse events per 10,000 vaccinations, they noted.

"These vaccination-associated risks are similar in rate and severity to the risks of hospitalized infections in our study. Hence, shingles vaccination before starting a TNF antagonist may not be warranted at present," they wrote, concluding that although vaccination in healthy children is warranted, it is not warranted in adults with "immunosuppression secondary to the baseline inflammatory disease and its complications."

Disclosures: Various study authors reported serving on the advisory board for, and/or receiving lecture fees or honoraria from, Wyeth, Abbott, Schering-Plough, Roche, and/or Bristol-Myers Squibb.

Rheumatic disease patients who are exposed to tumor necrosis factor antagonists have a 10-fold increased risk of hospitalization for varicella zoster virus infections, compared with the general population, according to a secondary analysis of two large databases.

Nonetheless, the absolute incidence of varicella-related hospitalizations remains low at about three cases per 10,000 person-years of exposure, and the risks of using vaccination for prevention likely outweigh the benefits, Dr. Ignacio Garcia-Doval of Complexo Hospitalario de Pontevedra (Spain) and colleagues have reported in the October issue of the Annals of the Rheumatic Diseases.

The estimated incidence rate of hospitalization for shingles in the rheumatic population was 32 cases per 100,000 patient years, compared with an expected rate of 3.4 in the general population, and the estimated incidence of hospitalization for chickenpox in the rheumatic patients was 26 per 100,000, compared with 1.9 in the general population. This finding is based on analysis of data from a national registry of rheumatic disease patients who were treated with TNF agents (BIOBADASER database) and from an administrative database of all hospital admissions in public centers in Spain (Conjunto Mínimo Básico de Datos al Alta Hospitalaria, or CMBD), which together represent more than 114 million patient-years.

The estimated age- and sex-standardized incidence rate per 100,000 person-years, and the estimated standardized incidence difference were 9 and 26, respectively, for shingles, and 19 and 33, respectively, for chickenpox, they said (Ann. Rheum. Dis. 2010;69:1751-5).

TNF antagonists are known to be associated with an increased risk of tuberculosis in particular and of opportunistic infections in general. There is a biological basis for an increased risk of viral infections, the investigators said, noting that although some studies have shown an increased rate of viral infection in TNF antagonist–treated patients, the clinical relevance of the increase is uncertain.

The current study does not allow differentiation of the causes for the increased risk, but it does show that the absolute rate is low.

The investigators said it is unlikely that the cohorts received systematic vaccination against varicella zoster virus, since the general health mandate in Spain was given in 2005 and only for children aged 11-14 years.

"Standard guidelines for chickenpox vaccination probably apply to the population included in our study," they wrote.

However, shingles vaccine, which is an attenuated vaccine with a higher dose of antigen, could potentially lead to more side effects in an immunosuppressed population, they said.

For example, in a randomized trial of adults older than age 60 years, shingles vaccine was associated with 7 cases of severe adverse events and 14 cases of vaccine-related adverse events per 10,000 vaccinations, they noted.

"These vaccination-associated risks are similar in rate and severity to the risks of hospitalized infections in our study. Hence, shingles vaccination before starting a TNF antagonist may not be warranted at present," they wrote, concluding that although vaccination in healthy children is warranted, it is not warranted in adults with "immunosuppression secondary to the baseline inflammatory disease and its complications."

Disclosures: Various study authors reported serving on the advisory board for, and/or receiving lecture fees or honoraria from, Wyeth, Abbott, Schering-Plough, Roche, and/or Bristol-Myers Squibb.

Rheumatic disease patients who are exposed to tumor necrosis factor antagonists have a 10-fold increased risk of hospitalization for varicella zoster virus infections, compared with the general population, according to a secondary analysis of two large databases.

Nonetheless, the absolute incidence of varicella-related hospitalizations remains low at about three cases per 10,000 person-years of exposure, and the risks of using vaccination for prevention likely outweigh the benefits, Dr. Ignacio Garcia-Doval of Complexo Hospitalario de Pontevedra (Spain) and colleagues have reported in the October issue of the Annals of the Rheumatic Diseases.

The estimated incidence rate of hospitalization for shingles in the rheumatic population was 32 cases per 100,000 patient years, compared with an expected rate of 3.4 in the general population, and the estimated incidence of hospitalization for chickenpox in the rheumatic patients was 26 per 100,000, compared with 1.9 in the general population. This finding is based on analysis of data from a national registry of rheumatic disease patients who were treated with TNF agents (BIOBADASER database) and from an administrative database of all hospital admissions in public centers in Spain (Conjunto Mínimo Básico de Datos al Alta Hospitalaria, or CMBD), which together represent more than 114 million patient-years.

The estimated age- and sex-standardized incidence rate per 100,000 person-years, and the estimated standardized incidence difference were 9 and 26, respectively, for shingles, and 19 and 33, respectively, for chickenpox, they said (Ann. Rheum. Dis. 2010;69:1751-5).

TNF antagonists are known to be associated with an increased risk of tuberculosis in particular and of opportunistic infections in general. There is a biological basis for an increased risk of viral infections, the investigators said, noting that although some studies have shown an increased rate of viral infection in TNF antagonist–treated patients, the clinical relevance of the increase is uncertain.

The current study does not allow differentiation of the causes for the increased risk, but it does show that the absolute rate is low.

The investigators said it is unlikely that the cohorts received systematic vaccination against varicella zoster virus, since the general health mandate in Spain was given in 2005 and only for children aged 11-14 years.

"Standard guidelines for chickenpox vaccination probably apply to the population included in our study," they wrote.

However, shingles vaccine, which is an attenuated vaccine with a higher dose of antigen, could potentially lead to more side effects in an immunosuppressed population, they said.

For example, in a randomized trial of adults older than age 60 years, shingles vaccine was associated with 7 cases of severe adverse events and 14 cases of vaccine-related adverse events per 10,000 vaccinations, they noted.

"These vaccination-associated risks are similar in rate and severity to the risks of hospitalized infections in our study. Hence, shingles vaccination before starting a TNF antagonist may not be warranted at present," they wrote, concluding that although vaccination in healthy children is warranted, it is not warranted in adults with "immunosuppression secondary to the baseline inflammatory disease and its complications."

Disclosures: Various study authors reported serving on the advisory board for, and/or receiving lecture fees or honoraria from, Wyeth, Abbott, Schering-Plough, Roche, and/or Bristol-Myers Squibb.

Suffering for fashion is a time-honored tradition, from bustles and corsets to sky-high heels and pointy toes. But psoriasis patients (approximately 7.5 million adults in the United States) suffer even more than most. And 80% have plaque-type psoriasis, which can make it especially tough to find clothes that don't irritate their skin, let alone clothes with style.

Fortunately, there are some fashion doctors in town: Tim Gunn, who mentors up-and-coming designers on "Project Runway," and Dr. Susan Taylor, founder of the Skin of Color Center at St. Luke’s and Roosevelt Hospitals in New York, Ny.

Courtesy flickr user zehhhra (Creative Commons)

In an online collection of videos called "Psophisticated Style: A Guide to Everyday Style and Psoriasis," Dr. Taylor and Gunn provide personalized fashion advice to five psoriasis patients. The patients were selected in a contest that was part of an ongoing "Addressing Psoriasis" public awareness campaign sponsored by Amgen and Pfizer (yes, both of these companies make psoriasis drugs, as if you had to ask).

The videos are fun, funky, and fashion-forward, with some style tips that anyone – psoriasis patient or not – can use.

The Fabulous Fabrics video includes suggestions about choosing breathable fabrics, such as cotton, linen, and silk. But, as Dr. Taylor notes, it's important to experiment with different fabrics, because what feels good to one person may not be comfortable for another, breathable or not. She mentioned how one of her patients prefers the feel of polyester to cotton, and simply makes an effort to stay in air-conditioned comfort when wearing it.

A key tip from the Awesome Accessories video reminds us about using scarves to update a look – and cleverly conceal problem plaques on the neck.

In the Seasonal Styling video, we learn to try gray instead of black for suits or dresses, because gray is less likely to show the skin flakes that are inevitable for many psoriasis patients.

And here's Gunn's tip on proportion and the rule of thirds: Don't let your outfit cut you exactly in half; it’s not a good look for anyone. I feel more stylish already!

Heidi Splete (on twitter @hsplete)

Suffering for fashion is a time-honored tradition, from bustles and corsets to sky-high heels and pointy toes. But psoriasis patients (approximately 7.5 million adults in the United States) suffer even more than most. And 80% have plaque-type psoriasis, which can make it especially tough to find clothes that don't irritate their skin, let alone clothes with style.

Fortunately, there are some fashion doctors in town: Tim Gunn, who mentors up-and-coming designers on "Project Runway," and Dr. Susan Taylor, founder of the Skin of Color Center at St. Luke’s and Roosevelt Hospitals in New York, Ny.

Courtesy flickr user zehhhra (Creative Commons)

In an online collection of videos called "Psophisticated Style: A Guide to Everyday Style and Psoriasis," Dr. Taylor and Gunn provide personalized fashion advice to five psoriasis patients. The patients were selected in a contest that was part of an ongoing "Addressing Psoriasis" public awareness campaign sponsored by Amgen and Pfizer (yes, both of these companies make psoriasis drugs, as if you had to ask).

The videos are fun, funky, and fashion-forward, with some style tips that anyone – psoriasis patient or not – can use.

The Fabulous Fabrics video includes suggestions about choosing breathable fabrics, such as cotton, linen, and silk. But, as Dr. Taylor notes, it's important to experiment with different fabrics, because what feels good to one person may not be comfortable for another, breathable or not. She mentioned how one of her patients prefers the feel of polyester to cotton, and simply makes an effort to stay in air-conditioned comfort when wearing it.

A key tip from the Awesome Accessories video reminds us about using scarves to update a look – and cleverly conceal problem plaques on the neck.

In the Seasonal Styling video, we learn to try gray instead of black for suits or dresses, because gray is less likely to show the skin flakes that are inevitable for many psoriasis patients.

And here's Gunn's tip on proportion and the rule of thirds: Don't let your outfit cut you exactly in half; it’s not a good look for anyone. I feel more stylish already!

Heidi Splete (on twitter @hsplete)

Suffering for fashion is a time-honored tradition, from bustles and corsets to sky-high heels and pointy toes. But psoriasis patients (approximately 7.5 million adults in the United States) suffer even more than most. And 80% have plaque-type psoriasis, which can make it especially tough to find clothes that don't irritate their skin, let alone clothes with style.

Fortunately, there are some fashion doctors in town: Tim Gunn, who mentors up-and-coming designers on "Project Runway," and Dr. Susan Taylor, founder of the Skin of Color Center at St. Luke’s and Roosevelt Hospitals in New York, Ny.

Courtesy flickr user zehhhra (Creative Commons)

In an online collection of videos called "Psophisticated Style: A Guide to Everyday Style and Psoriasis," Dr. Taylor and Gunn provide personalized fashion advice to five psoriasis patients. The patients were selected in a contest that was part of an ongoing "Addressing Psoriasis" public awareness campaign sponsored by Amgen and Pfizer (yes, both of these companies make psoriasis drugs, as if you had to ask).

The videos are fun, funky, and fashion-forward, with some style tips that anyone – psoriasis patient or not – can use.

The Fabulous Fabrics video includes suggestions about choosing breathable fabrics, such as cotton, linen, and silk. But, as Dr. Taylor notes, it's important to experiment with different fabrics, because what feels good to one person may not be comfortable for another, breathable or not. She mentioned how one of her patients prefers the feel of polyester to cotton, and simply makes an effort to stay in air-conditioned comfort when wearing it.

A key tip from the Awesome Accessories video reminds us about using scarves to update a look – and cleverly conceal problem plaques on the neck.

In the Seasonal Styling video, we learn to try gray instead of black for suits or dresses, because gray is less likely to show the skin flakes that are inevitable for many psoriasis patients.

And here's Gunn's tip on proportion and the rule of thirds: Don't let your outfit cut you exactly in half; it’s not a good look for anyone. I feel more stylish already!

Heidi Splete (on twitter @hsplete)

Treatment with bosentan reduced the occurrence of new ischemic digital ulcers in patients with systemic sclerosis, but did not hasten healing of existing ulcers, findings from a study have shown.

The dual endothelin receptor antagonist was associated with a 30% reduction in the number of new digital ulcers in a double-blind, placebo-controlled trial reported online in the Annals of the Rheumatic Diseases.

Photo courtesy Dr. James R. Seibold

In the United States, the Food and Drug Administration has approved bosentan (Tracleer) for the treatment of pulmonary artery hypertension (PAH). Both PAH and digital ulcers are complications of systemic sclerosis (SSc). In Europe, bosentan is approved for pulmonary artery hypertension.

As a follow-up to a previous study of 122 SSc patients in whom bosentan treatment was associated with a 48% reduction, compared with placebo, in the mean number of new digital ulcers but no differences in healing after 16 weeks of treatment, Dr. Marco Matucci-Cerinic, professor of rheumatology and medicine at the University of Florence (Italy) and colleagues designed the current trial to evaluate the effects of the drug in a larger population of patients over a longer period of time.

Toward this end, the investigators enrolled 188 SSc patients with at least one active digital ulcer (the cardinal ulcer) to receive 62.5 mg of bosentan twice daily for 4 weeks and 125 mg twice daily for 20 weeks, or matching placebo.

Patients in both groups were at least 18 years old at the time of enrollment (between October 2003 and May 2005) and were well matched with respect to demographics, baseline disease characteristics, and concomitant treatment for digital ulcers at baseline.

The study's primary end points were the number of new digital ulcers and the time to healing of the cardinal ulcer; the secondary end points were pain, disability, and safety, the authors wrote (Ann. Rheum. Dis. 2010 Aug. 30 [doi:10.1136/ard.2010.130658]).

After 24 weeks, the mean total number of digital ulcers per patient was similar in the two groups, but the mean number of new digital ulcers was 1.9 in the treatment group and 2.7 in the placebo group, the authors reported. "Fewer new [digital ulcers] were observed with bosentan than placebo in all subgroups except among current smokers," they stated. "This included subgroups of limited and diffuse [SSc], with no difference between the two subgroups in the treatment effect."

In post hoc analysis, more pronounced reductions were seen in patients who had multiple digital ulcers, the authors observed. Specifically, they wrote, "the reduction of new [digital ulcers] appeared to be greater in patients with at least four [digital ulcers] at baseline."

The reduction of new digital ulcers in bosentan-treated patients "did not translate into a smaller ulcer burden, as was seen in the previous study," the authors stated, noting that this could be attributed to the fact that 38% of patients in the previous study did not have an active digital ulcer at baseline and had fewer digital ulcers to heal, possibly giving more weight to prevention in the reduction of overall ulcer burden.

In terms of healing, there was no difference in the time to healing of the cardinal ulcer between bosentan treatment and placebo. At 24 weeks, more than half of the patients in both groups had healing of the cardinal ulcer that was maintained for a minimum of 12 weeks, the authors wrote.

Additionally, no treatment effects were observed in patient-rated measures of overall hand pain and pain of the cardinal ulcer, as assessed by visual analog scales. Similarly, there were no significant differences in the changes from baseline in the Health Assessment Questionnaire–Disability Index and hand disability index at week 24, they reported.

The fact that the reduction in new ulcers was not associated with decreased pain or disability, relative to placebo, could be explained by the similar number of digital ulcers between treatment groups, or a lack of sensitivity to change and discriminative value in the current instruments that are used to assess hand function in systemic sclerosis, the authors hypothesized. It might also be indicative of the fact that bosentan treatment does not improve pain and disability in spite of the reduction of new digital ulcers, they wrote.

Safety and tolerability assessments showed that serious adverse events occurred in 9.4% and 16.7%, respectively, of patients in the bosentan and placebo groups, and that similar proportions of patients in both groups experienced at least one adverse event, the authors reported. More treatment vs. placebo patients experienced peripheral edema and events denoting elevated aminotransferases.

Laboratory analyses showed increases in aminotransferases in 10.5% of the bosentan patients, compared with 1.1% of the placebo patients, reinforcing "the need for continual monitoring of liver function with this treatment," the authors wrote.

The clinical utility of bosentan treatment for digital ulcer prevention in SSc "may be challenged," the authors wrote. "In a patient encountered with a single [digital ulcer], initiation of bosentan would not be expected to facilitate healing, and at least 66% of all bosentan-treated subjects would develop at least one additional [digital ulcer] over 6 months of follow-up." However, they noted, bosentan treatment offers greater potential benefit to patients who present with multiple digital ulcers. In this regard, the treatment "may be a useful adjunct in the management of patients with [SSc] and recurrent [digital ulcers]."

Disclosures: This study was funded by Actelion Pharmaceuticals. The authors disclosed financial relationships with Actelion, Pfizer, GlaxoSmithKline Beecham, Encysive, Genzyme, Aspreva, Biovitrum, DiGNA, Gilead, MediQuest, Centocor, FibroGen, Bristol-Myers Squibb, Lilly, and United Therapeutics.

Treatment with bosentan reduced the occurrence of new ischemic digital ulcers in patients with systemic sclerosis, but did not hasten healing of existing ulcers, findings from a study have shown.

The dual endothelin receptor antagonist was associated with a 30% reduction in the number of new digital ulcers in a double-blind, placebo-controlled trial reported online in the Annals of the Rheumatic Diseases.

Photo courtesy Dr. James R. Seibold

In the United States, the Food and Drug Administration has approved bosentan (Tracleer) for the treatment of pulmonary artery hypertension (PAH). Both PAH and digital ulcers are complications of systemic sclerosis (SSc). In Europe, bosentan is approved for pulmonary artery hypertension.

As a follow-up to a previous study of 122 SSc patients in whom bosentan treatment was associated with a 48% reduction, compared with placebo, in the mean number of new digital ulcers but no differences in healing after 16 weeks of treatment, Dr. Marco Matucci-Cerinic, professor of rheumatology and medicine at the University of Florence (Italy) and colleagues designed the current trial to evaluate the effects of the drug in a larger population of patients over a longer period of time.

Toward this end, the investigators enrolled 188 SSc patients with at least one active digital ulcer (the cardinal ulcer) to receive 62.5 mg of bosentan twice daily for 4 weeks and 125 mg twice daily for 20 weeks, or matching placebo.

Patients in both groups were at least 18 years old at the time of enrollment (between October 2003 and May 2005) and were well matched with respect to demographics, baseline disease characteristics, and concomitant treatment for digital ulcers at baseline.

The study's primary end points were the number of new digital ulcers and the time to healing of the cardinal ulcer; the secondary end points were pain, disability, and safety, the authors wrote (Ann. Rheum. Dis. 2010 Aug. 30 [doi:10.1136/ard.2010.130658]).

After 24 weeks, the mean total number of digital ulcers per patient was similar in the two groups, but the mean number of new digital ulcers was 1.9 in the treatment group and 2.7 in the placebo group, the authors reported. "Fewer new [digital ulcers] were observed with bosentan than placebo in all subgroups except among current smokers," they stated. "This included subgroups of limited and diffuse [SSc], with no difference between the two subgroups in the treatment effect."

In post hoc analysis, more pronounced reductions were seen in patients who had multiple digital ulcers, the authors observed. Specifically, they wrote, "the reduction of new [digital ulcers] appeared to be greater in patients with at least four [digital ulcers] at baseline."

The reduction of new digital ulcers in bosentan-treated patients "did not translate into a smaller ulcer burden, as was seen in the previous study," the authors stated, noting that this could be attributed to the fact that 38% of patients in the previous study did not have an active digital ulcer at baseline and had fewer digital ulcers to heal, possibly giving more weight to prevention in the reduction of overall ulcer burden.

In terms of healing, there was no difference in the time to healing of the cardinal ulcer between bosentan treatment and placebo. At 24 weeks, more than half of the patients in both groups had healing of the cardinal ulcer that was maintained for a minimum of 12 weeks, the authors wrote.

Additionally, no treatment effects were observed in patient-rated measures of overall hand pain and pain of the cardinal ulcer, as assessed by visual analog scales. Similarly, there were no significant differences in the changes from baseline in the Health Assessment Questionnaire–Disability Index and hand disability index at week 24, they reported.

The fact that the reduction in new ulcers was not associated with decreased pain or disability, relative to placebo, could be explained by the similar number of digital ulcers between treatment groups, or a lack of sensitivity to change and discriminative value in the current instruments that are used to assess hand function in systemic sclerosis, the authors hypothesized. It might also be indicative of the fact that bosentan treatment does not improve pain and disability in spite of the reduction of new digital ulcers, they wrote.

Safety and tolerability assessments showed that serious adverse events occurred in 9.4% and 16.7%, respectively, of patients in the bosentan and placebo groups, and that similar proportions of patients in both groups experienced at least one adverse event, the authors reported. More treatment vs. placebo patients experienced peripheral edema and events denoting elevated aminotransferases.

Laboratory analyses showed increases in aminotransferases in 10.5% of the bosentan patients, compared with 1.1% of the placebo patients, reinforcing "the need for continual monitoring of liver function with this treatment," the authors wrote.

The clinical utility of bosentan treatment for digital ulcer prevention in SSc "may be challenged," the authors wrote. "In a patient encountered with a single [digital ulcer], initiation of bosentan would not be expected to facilitate healing, and at least 66% of all bosentan-treated subjects would develop at least one additional [digital ulcer] over 6 months of follow-up." However, they noted, bosentan treatment offers greater potential benefit to patients who present with multiple digital ulcers. In this regard, the treatment "may be a useful adjunct in the management of patients with [SSc] and recurrent [digital ulcers]."

Disclosures: This study was funded by Actelion Pharmaceuticals. The authors disclosed financial relationships with Actelion, Pfizer, GlaxoSmithKline Beecham, Encysive, Genzyme, Aspreva, Biovitrum, DiGNA, Gilead, MediQuest, Centocor, FibroGen, Bristol-Myers Squibb, Lilly, and United Therapeutics.

Treatment with bosentan reduced the occurrence of new ischemic digital ulcers in patients with systemic sclerosis, but did not hasten healing of existing ulcers, findings from a study have shown.

The dual endothelin receptor antagonist was associated with a 30% reduction in the number of new digital ulcers in a double-blind, placebo-controlled trial reported online in the Annals of the Rheumatic Diseases.

Photo courtesy Dr. James R. Seibold

In the United States, the Food and Drug Administration has approved bosentan (Tracleer) for the treatment of pulmonary artery hypertension (PAH). Both PAH and digital ulcers are complications of systemic sclerosis (SSc). In Europe, bosentan is approved for pulmonary artery hypertension.

As a follow-up to a previous study of 122 SSc patients in whom bosentan treatment was associated with a 48% reduction, compared with placebo, in the mean number of new digital ulcers but no differences in healing after 16 weeks of treatment, Dr. Marco Matucci-Cerinic, professor of rheumatology and medicine at the University of Florence (Italy) and colleagues designed the current trial to evaluate the effects of the drug in a larger population of patients over a longer period of time.

Toward this end, the investigators enrolled 188 SSc patients with at least one active digital ulcer (the cardinal ulcer) to receive 62.5 mg of bosentan twice daily for 4 weeks and 125 mg twice daily for 20 weeks, or matching placebo.

Patients in both groups were at least 18 years old at the time of enrollment (between October 2003 and May 2005) and were well matched with respect to demographics, baseline disease characteristics, and concomitant treatment for digital ulcers at baseline.

The study's primary end points were the number of new digital ulcers and the time to healing of the cardinal ulcer; the secondary end points were pain, disability, and safety, the authors wrote (Ann. Rheum. Dis. 2010 Aug. 30 [doi:10.1136/ard.2010.130658]).

After 24 weeks, the mean total number of digital ulcers per patient was similar in the two groups, but the mean number of new digital ulcers was 1.9 in the treatment group and 2.7 in the placebo group, the authors reported. "Fewer new [digital ulcers] were observed with bosentan than placebo in all subgroups except among current smokers," they stated. "This included subgroups of limited and diffuse [SSc], with no difference between the two subgroups in the treatment effect."

In post hoc analysis, more pronounced reductions were seen in patients who had multiple digital ulcers, the authors observed. Specifically, they wrote, "the reduction of new [digital ulcers] appeared to be greater in patients with at least four [digital ulcers] at baseline."

The reduction of new digital ulcers in bosentan-treated patients "did not translate into a smaller ulcer burden, as was seen in the previous study," the authors stated, noting that this could be attributed to the fact that 38% of patients in the previous study did not have an active digital ulcer at baseline and had fewer digital ulcers to heal, possibly giving more weight to prevention in the reduction of overall ulcer burden.

In terms of healing, there was no difference in the time to healing of the cardinal ulcer between bosentan treatment and placebo. At 24 weeks, more than half of the patients in both groups had healing of the cardinal ulcer that was maintained for a minimum of 12 weeks, the authors wrote.

Additionally, no treatment effects were observed in patient-rated measures of overall hand pain and pain of the cardinal ulcer, as assessed by visual analog scales. Similarly, there were no significant differences in the changes from baseline in the Health Assessment Questionnaire–Disability Index and hand disability index at week 24, they reported.

The fact that the reduction in new ulcers was not associated with decreased pain or disability, relative to placebo, could be explained by the similar number of digital ulcers between treatment groups, or a lack of sensitivity to change and discriminative value in the current instruments that are used to assess hand function in systemic sclerosis, the authors hypothesized. It might also be indicative of the fact that bosentan treatment does not improve pain and disability in spite of the reduction of new digital ulcers, they wrote.

Safety and tolerability assessments showed that serious adverse events occurred in 9.4% and 16.7%, respectively, of patients in the bosentan and placebo groups, and that similar proportions of patients in both groups experienced at least one adverse event, the authors reported. More treatment vs. placebo patients experienced peripheral edema and events denoting elevated aminotransferases.

Laboratory analyses showed increases in aminotransferases in 10.5% of the bosentan patients, compared with 1.1% of the placebo patients, reinforcing "the need for continual monitoring of liver function with this treatment," the authors wrote.

The clinical utility of bosentan treatment for digital ulcer prevention in SSc "may be challenged," the authors wrote. "In a patient encountered with a single [digital ulcer], initiation of bosentan would not be expected to facilitate healing, and at least 66% of all bosentan-treated subjects would develop at least one additional [digital ulcer] over 6 months of follow-up." However, they noted, bosentan treatment offers greater potential benefit to patients who present with multiple digital ulcers. In this regard, the treatment "may be a useful adjunct in the management of patients with [SSc] and recurrent [digital ulcers]."

Disclosures: This study was funded by Actelion Pharmaceuticals. The authors disclosed financial relationships with Actelion, Pfizer, GlaxoSmithKline Beecham, Encysive, Genzyme, Aspreva, Biovitrum, DiGNA, Gilead, MediQuest, Centocor, FibroGen, Bristol-Myers Squibb, Lilly, and United Therapeutics.