Antimalarial Response in CLE Takes Time

BOSTON – The use of adjunctive therapy and a lot of patience may go a long way to improving the response of cutaneous lupus erythematosus to antimalarial agents, according to Dr. Jennie T. Clarke.

Antimalarials are the go-to treatment for cutaneous lupus erythematosus (CLE), yet roughly a third of patients do not respond, said Dr. Clarke, who spoke at the American Academy of Dermatology’s Summer Academy Meeting.

Findings from some recent studies shed light on how to improve that dismal response rate. In one of these trials involving 128 patients with CLE, researchers found that slightly more than half of patients who initiated treatment with hydroxychloroquine monotherapy were responders (55%) (Arch. Dermatol. 2011;147:1261-7). When quinacrine was added to the treatment regimen of the nonresponders, two-thirds experienced a lessening of their disease. Improvement continued beyond 2 months in 43%.

"With antimalarials remember that patience is important. [These agents] have a slow onset. You have to give the drugs for 2-3 months before assessing for efficacy. Patients need to know this because otherwise they’re going to become frustrated and noncompliant," said Dr. Clarke of the department of dermatology at Pennsylvania State University, Hershey.

The other important lesson from the study is about combination antimalarial therapy. Quinacrine can be added to either hydroxychloroquine or chloroquine to achieve improvement in patients who don’t respond to a single antimalarial agent.

However, roughly a third of patients don’t respond to a combination of antimalarials. Some research in the last 18 months has tried to identify which patients fail antimalarial treatment and why, in order to improve subsequent treatment. Three possible reasons have been identified: dosing and compliance, disease severity, and smoking status.

Bioavailability and clearance of hydroxychloroquine seems to vary by individual, she said. In addition, noncompliance is estimated to be about 10%. In a study of 300 CLE patients, French researchers found that the median blood concentration of hydroxychloroquine correlated with response (Arch. Dermatol. 2012;148:479-84). Specifically, the median blood hydroxychloroquine concentration was significantly higher in patients with complete remission compared with those with either partial remission or treatment failure. Findings from the multivariate analysis showed that complete remission was associated with higher blood hydroxychloroquine concentrations and the absence of discoid lesions.

Concentration and response were correlated with actual rather than ideal body weight dosing. Smoking was not found to be related to concentration, and the subset of 170 patients with discoid lupus erythematosus (DLE) was less responsive to hydroxychloroquine.

Thirty patients (10%) had very low blood hydroxychloroquine concentrations (less than 200 ng/mL) and may be considered nonadherent to the treatment regimen, Dr. Clarke noted. However, additional study is needed to determine the optimal blood concentration of hydroxychloroquine and the impact of toxicity with actual weight-based dosing rather than ideal body weight dosing.

In another study, researchers assessed the clinical and pharmacogenic influences of disease severity on response to blood concentration of hydroxychloroquine (J. Invest. Dermatol. 2011;131:1981-6). They assessed 200 patients with DLE. Slightly more than a third (35%) of patients had not responded to hydroxychloroquine at 6 months. Poor response was associated with disease severity and concomitant systemic lupus erythematosus (SLE). However, response was not associated with the presence of cytochrome P450 genotype or smoking.

It has been long held medical dogma that smoking lessens patients’ response to antimalarial drugs. The impact of smoking in patients with CLE was assessed directly in another paper (Arch. Dermatol. 2012;148:317-22). The researchers included 218 patients with CLE or SLE with skin disease. They found that current smokers had more severe disease and poorer disease-related quality of life. Smokers were also more likely to receive combination antimalarial therapy. Current smokers responded better to antimalarials than past or never smokers. However, smokers responded worse than nonsmokers if antimalarials and immunomodulator/suppressives were required.

"This tells us that antimalarials can be effective for smokers, particularly in those with more mild disease. But we need to remember that smokers who don’t respond are likely going to have poorer outcomes than nonsmokers who don’t respond to antimalarials."

Dr. Clarke reported having no relevant financial conflicts.

BOSTON – The use of adjunctive therapy and a lot of patience may go a long way to improving the response of cutaneous lupus erythematosus to antimalarial agents, according to Dr. Jennie T. Clarke.

Antimalarials are the go-to treatment for cutaneous lupus erythematosus (CLE), yet roughly a third of patients do not respond, said Dr. Clarke, who spoke at the American Academy of Dermatology’s Summer Academy Meeting.

Findings from some recent studies shed light on how to improve that dismal response rate. In one of these trials involving 128 patients with CLE, researchers found that slightly more than half of patients who initiated treatment with hydroxychloroquine monotherapy were responders (55%) (Arch. Dermatol. 2011;147:1261-7). When quinacrine was added to the treatment regimen of the nonresponders, two-thirds experienced a lessening of their disease. Improvement continued beyond 2 months in 43%.

"With antimalarials remember that patience is important. [These agents] have a slow onset. You have to give the drugs for 2-3 months before assessing for efficacy. Patients need to know this because otherwise they’re going to become frustrated and noncompliant," said Dr. Clarke of the department of dermatology at Pennsylvania State University, Hershey.

The other important lesson from the study is about combination antimalarial therapy. Quinacrine can be added to either hydroxychloroquine or chloroquine to achieve improvement in patients who don’t respond to a single antimalarial agent.

However, roughly a third of patients don’t respond to a combination of antimalarials. Some research in the last 18 months has tried to identify which patients fail antimalarial treatment and why, in order to improve subsequent treatment. Three possible reasons have been identified: dosing and compliance, disease severity, and smoking status.

Bioavailability and clearance of hydroxychloroquine seems to vary by individual, she said. In addition, noncompliance is estimated to be about 10%. In a study of 300 CLE patients, French researchers found that the median blood concentration of hydroxychloroquine correlated with response (Arch. Dermatol. 2012;148:479-84). Specifically, the median blood hydroxychloroquine concentration was significantly higher in patients with complete remission compared with those with either partial remission or treatment failure. Findings from the multivariate analysis showed that complete remission was associated with higher blood hydroxychloroquine concentrations and the absence of discoid lesions.

Concentration and response were correlated with actual rather than ideal body weight dosing. Smoking was not found to be related to concentration, and the subset of 170 patients with discoid lupus erythematosus (DLE) was less responsive to hydroxychloroquine.

Thirty patients (10%) had very low blood hydroxychloroquine concentrations (less than 200 ng/mL) and may be considered nonadherent to the treatment regimen, Dr. Clarke noted. However, additional study is needed to determine the optimal blood concentration of hydroxychloroquine and the impact of toxicity with actual weight-based dosing rather than ideal body weight dosing.

In another study, researchers assessed the clinical and pharmacogenic influences of disease severity on response to blood concentration of hydroxychloroquine (J. Invest. Dermatol. 2011;131:1981-6). They assessed 200 patients with DLE. Slightly more than a third (35%) of patients had not responded to hydroxychloroquine at 6 months. Poor response was associated with disease severity and concomitant systemic lupus erythematosus (SLE). However, response was not associated with the presence of cytochrome P450 genotype or smoking.

It has been long held medical dogma that smoking lessens patients’ response to antimalarial drugs. The impact of smoking in patients with CLE was assessed directly in another paper (Arch. Dermatol. 2012;148:317-22). The researchers included 218 patients with CLE or SLE with skin disease. They found that current smokers had more severe disease and poorer disease-related quality of life. Smokers were also more likely to receive combination antimalarial therapy. Current smokers responded better to antimalarials than past or never smokers. However, smokers responded worse than nonsmokers if antimalarials and immunomodulator/suppressives were required.

"This tells us that antimalarials can be effective for smokers, particularly in those with more mild disease. But we need to remember that smokers who don’t respond are likely going to have poorer outcomes than nonsmokers who don’t respond to antimalarials."

Dr. Clarke reported having no relevant financial conflicts.

BOSTON – The use of adjunctive therapy and a lot of patience may go a long way to improving the response of cutaneous lupus erythematosus to antimalarial agents, according to Dr. Jennie T. Clarke.

Antimalarials are the go-to treatment for cutaneous lupus erythematosus (CLE), yet roughly a third of patients do not respond, said Dr. Clarke, who spoke at the American Academy of Dermatology’s Summer Academy Meeting.

Findings from some recent studies shed light on how to improve that dismal response rate. In one of these trials involving 128 patients with CLE, researchers found that slightly more than half of patients who initiated treatment with hydroxychloroquine monotherapy were responders (55%) (Arch. Dermatol. 2011;147:1261-7). When quinacrine was added to the treatment regimen of the nonresponders, two-thirds experienced a lessening of their disease. Improvement continued beyond 2 months in 43%.

"With antimalarials remember that patience is important. [These agents] have a slow onset. You have to give the drugs for 2-3 months before assessing for efficacy. Patients need to know this because otherwise they’re going to become frustrated and noncompliant," said Dr. Clarke of the department of dermatology at Pennsylvania State University, Hershey.

The other important lesson from the study is about combination antimalarial therapy. Quinacrine can be added to either hydroxychloroquine or chloroquine to achieve improvement in patients who don’t respond to a single antimalarial agent.

However, roughly a third of patients don’t respond to a combination of antimalarials. Some research in the last 18 months has tried to identify which patients fail antimalarial treatment and why, in order to improve subsequent treatment. Three possible reasons have been identified: dosing and compliance, disease severity, and smoking status.

Bioavailability and clearance of hydroxychloroquine seems to vary by individual, she said. In addition, noncompliance is estimated to be about 10%. In a study of 300 CLE patients, French researchers found that the median blood concentration of hydroxychloroquine correlated with response (Arch. Dermatol. 2012;148:479-84). Specifically, the median blood hydroxychloroquine concentration was significantly higher in patients with complete remission compared with those with either partial remission or treatment failure. Findings from the multivariate analysis showed that complete remission was associated with higher blood hydroxychloroquine concentrations and the absence of discoid lesions.

Concentration and response were correlated with actual rather than ideal body weight dosing. Smoking was not found to be related to concentration, and the subset of 170 patients with discoid lupus erythematosus (DLE) was less responsive to hydroxychloroquine.

Thirty patients (10%) had very low blood hydroxychloroquine concentrations (less than 200 ng/mL) and may be considered nonadherent to the treatment regimen, Dr. Clarke noted. However, additional study is needed to determine the optimal blood concentration of hydroxychloroquine and the impact of toxicity with actual weight-based dosing rather than ideal body weight dosing.

In another study, researchers assessed the clinical and pharmacogenic influences of disease severity on response to blood concentration of hydroxychloroquine (J. Invest. Dermatol. 2011;131:1981-6). They assessed 200 patients with DLE. Slightly more than a third (35%) of patients had not responded to hydroxychloroquine at 6 months. Poor response was associated with disease severity and concomitant systemic lupus erythematosus (SLE). However, response was not associated with the presence of cytochrome P450 genotype or smoking.

It has been long held medical dogma that smoking lessens patients’ response to antimalarial drugs. The impact of smoking in patients with CLE was assessed directly in another paper (Arch. Dermatol. 2012;148:317-22). The researchers included 218 patients with CLE or SLE with skin disease. They found that current smokers had more severe disease and poorer disease-related quality of life. Smokers were also more likely to receive combination antimalarial therapy. Current smokers responded better to antimalarials than past or never smokers. However, smokers responded worse than nonsmokers if antimalarials and immunomodulator/suppressives were required.

"This tells us that antimalarials can be effective for smokers, particularly in those with more mild disease. But we need to remember that smokers who don’t respond are likely going to have poorer outcomes than nonsmokers who don’t respond to antimalarials."

Dr. Clarke reported having no relevant financial conflicts.