User login
Severe hydroxychloroquine nonadherence linked to worse SLE outcomes
SEOUL, SOUTH KOREA – Regular testing of hydroxychloroquine levels in patients with systemic lupus erythematosus – especially those who are experiencing a disease flare – could help to identify patients who are not taking their treatment and are at risk of worse outcomes.
Data presented at an international congress on systemic lupus erythematosus showed that 7.3% of patients with SLE are severely nonadherent to their medication and have a higher risk of flare, early damage, and mortality.
Rheumatologist Nathalie Costedoat-Chalumeau, MD, PhD, professor of internal medicine at Cochin Hospital, Paris, presented data from 660 patients enrolled in the international longitudinal SLICC Inception Cohort, who had all been on hydroxychloroquine therapy for at least 3 months at baseline.
Patients’ serum hydroxychloroquine levels were measured at baseline and follow-up, and severe nonadherence was defined as below 106 ng/mL for those on 400 mg/day or 53 ng/mL for those on 200 mg/day.
Dr. Costedoat-Chalumeau said that those thresholds were chosen based on earlier work that analyzed the blood concentration of hydroxychloroquine in a group of patients and identified a group with very low concentrations corresponding to severe nonadherence.
“Since then, it has been reproduced by others with the same threshold,” she said. “When you have very low levels of hydroxychloroquine in their blood, you know that your patients don’t take their treatment.”
In the present study, the 7.3% of patients who met the criteria for severe nonadherence had a significant 3.3-fold higher risk of disease flare within a year of enrollment than did those who were adherent. They also had significantly higher mortality at 5 years after enrollment.
While the study didn’t show a significant difference in the level of damage at 5 years – defined as a worsening of their SLICC damage index – Dr. Costedoat-Chalumeau said they saw significantly greater damage occurring at 1, 2, and 3 years after enrollment among those who were severely nonadherent.
The challenge with recognizing these nonadherent patients is that they have no obvious differences at baseline from those who are adherent, Dr. Costedoat-Chalumeau said. The rates of nonadherence were similar regardless of what dose the patient was on, their ethnicity, gender, education level, or other demographic variables.
“I believe strongly that there is a benefit of testing hydroxychloroquine levels in the blood or serum to detect severe nonadherence,” she said.
At Dr. Costedoat-Chalumeau’s clinic, patients’ hydroxychloroquine levels are tested at every clinic visit, she said in an interview, and especially if they are experiencing a disease flare. “We want to know if the flare is because the patient is not taking the treatment or if it’s because the treatment is not effective, which is very different in terms of management,” she said. She recommended waiting at least 1 month after patients start treatment before measuring their hydroxychloroquine levels.
As to why some patients choose to stop taking their medication, Dr. Costedoat-Chalumeau said sometimes it was because patients were worried about side effects, but others were also unclear about why they needed to keep taking hydroxychloroquine.
“They think steroids are effective because when they take it they are better, but they don’t see the effect of hydroxychloroquine,” she said. “You have to explain that it doesn’t work the same.”
Commenting on the findings, session chair Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said the data show that severe nonadherence does have prognostic significance. “Many patients with SLE have low-grade disease or inflammation in the blood vessels that may not be clinically apparent and which hydroxychloroquine can help, so it might be wise to routinely get blood levels,” she said.
Dr. Costedoat-Chalumeau reported no relevant financial relationships apart from unrestricted institutional research grants from UCB and Roche.
SEOUL, SOUTH KOREA – Regular testing of hydroxychloroquine levels in patients with systemic lupus erythematosus – especially those who are experiencing a disease flare – could help to identify patients who are not taking their treatment and are at risk of worse outcomes.
Data presented at an international congress on systemic lupus erythematosus showed that 7.3% of patients with SLE are severely nonadherent to their medication and have a higher risk of flare, early damage, and mortality.
Rheumatologist Nathalie Costedoat-Chalumeau, MD, PhD, professor of internal medicine at Cochin Hospital, Paris, presented data from 660 patients enrolled in the international longitudinal SLICC Inception Cohort, who had all been on hydroxychloroquine therapy for at least 3 months at baseline.
Patients’ serum hydroxychloroquine levels were measured at baseline and follow-up, and severe nonadherence was defined as below 106 ng/mL for those on 400 mg/day or 53 ng/mL for those on 200 mg/day.
Dr. Costedoat-Chalumeau said that those thresholds were chosen based on earlier work that analyzed the blood concentration of hydroxychloroquine in a group of patients and identified a group with very low concentrations corresponding to severe nonadherence.
“Since then, it has been reproduced by others with the same threshold,” she said. “When you have very low levels of hydroxychloroquine in their blood, you know that your patients don’t take their treatment.”
In the present study, the 7.3% of patients who met the criteria for severe nonadherence had a significant 3.3-fold higher risk of disease flare within a year of enrollment than did those who were adherent. They also had significantly higher mortality at 5 years after enrollment.
While the study didn’t show a significant difference in the level of damage at 5 years – defined as a worsening of their SLICC damage index – Dr. Costedoat-Chalumeau said they saw significantly greater damage occurring at 1, 2, and 3 years after enrollment among those who were severely nonadherent.
The challenge with recognizing these nonadherent patients is that they have no obvious differences at baseline from those who are adherent, Dr. Costedoat-Chalumeau said. The rates of nonadherence were similar regardless of what dose the patient was on, their ethnicity, gender, education level, or other demographic variables.
“I believe strongly that there is a benefit of testing hydroxychloroquine levels in the blood or serum to detect severe nonadherence,” she said.
At Dr. Costedoat-Chalumeau’s clinic, patients’ hydroxychloroquine levels are tested at every clinic visit, she said in an interview, and especially if they are experiencing a disease flare. “We want to know if the flare is because the patient is not taking the treatment or if it’s because the treatment is not effective, which is very different in terms of management,” she said. She recommended waiting at least 1 month after patients start treatment before measuring their hydroxychloroquine levels.
As to why some patients choose to stop taking their medication, Dr. Costedoat-Chalumeau said sometimes it was because patients were worried about side effects, but others were also unclear about why they needed to keep taking hydroxychloroquine.
“They think steroids are effective because when they take it they are better, but they don’t see the effect of hydroxychloroquine,” she said. “You have to explain that it doesn’t work the same.”
Commenting on the findings, session chair Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said the data show that severe nonadherence does have prognostic significance. “Many patients with SLE have low-grade disease or inflammation in the blood vessels that may not be clinically apparent and which hydroxychloroquine can help, so it might be wise to routinely get blood levels,” she said.
Dr. Costedoat-Chalumeau reported no relevant financial relationships apart from unrestricted institutional research grants from UCB and Roche.
SEOUL, SOUTH KOREA – Regular testing of hydroxychloroquine levels in patients with systemic lupus erythematosus – especially those who are experiencing a disease flare – could help to identify patients who are not taking their treatment and are at risk of worse outcomes.
Data presented at an international congress on systemic lupus erythematosus showed that 7.3% of patients with SLE are severely nonadherent to their medication and have a higher risk of flare, early damage, and mortality.
Rheumatologist Nathalie Costedoat-Chalumeau, MD, PhD, professor of internal medicine at Cochin Hospital, Paris, presented data from 660 patients enrolled in the international longitudinal SLICC Inception Cohort, who had all been on hydroxychloroquine therapy for at least 3 months at baseline.
Patients’ serum hydroxychloroquine levels were measured at baseline and follow-up, and severe nonadherence was defined as below 106 ng/mL for those on 400 mg/day or 53 ng/mL for those on 200 mg/day.
Dr. Costedoat-Chalumeau said that those thresholds were chosen based on earlier work that analyzed the blood concentration of hydroxychloroquine in a group of patients and identified a group with very low concentrations corresponding to severe nonadherence.
“Since then, it has been reproduced by others with the same threshold,” she said. “When you have very low levels of hydroxychloroquine in their blood, you know that your patients don’t take their treatment.”
In the present study, the 7.3% of patients who met the criteria for severe nonadherence had a significant 3.3-fold higher risk of disease flare within a year of enrollment than did those who were adherent. They also had significantly higher mortality at 5 years after enrollment.
While the study didn’t show a significant difference in the level of damage at 5 years – defined as a worsening of their SLICC damage index – Dr. Costedoat-Chalumeau said they saw significantly greater damage occurring at 1, 2, and 3 years after enrollment among those who were severely nonadherent.
The challenge with recognizing these nonadherent patients is that they have no obvious differences at baseline from those who are adherent, Dr. Costedoat-Chalumeau said. The rates of nonadherence were similar regardless of what dose the patient was on, their ethnicity, gender, education level, or other demographic variables.
“I believe strongly that there is a benefit of testing hydroxychloroquine levels in the blood or serum to detect severe nonadherence,” she said.
At Dr. Costedoat-Chalumeau’s clinic, patients’ hydroxychloroquine levels are tested at every clinic visit, she said in an interview, and especially if they are experiencing a disease flare. “We want to know if the flare is because the patient is not taking the treatment or if it’s because the treatment is not effective, which is very different in terms of management,” she said. She recommended waiting at least 1 month after patients start treatment before measuring their hydroxychloroquine levels.
As to why some patients choose to stop taking their medication, Dr. Costedoat-Chalumeau said sometimes it was because patients were worried about side effects, but others were also unclear about why they needed to keep taking hydroxychloroquine.
“They think steroids are effective because when they take it they are better, but they don’t see the effect of hydroxychloroquine,” she said. “You have to explain that it doesn’t work the same.”
Commenting on the findings, session chair Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said the data show that severe nonadherence does have prognostic significance. “Many patients with SLE have low-grade disease or inflammation in the blood vessels that may not be clinically apparent and which hydroxychloroquine can help, so it might be wise to routinely get blood levels,” she said.
Dr. Costedoat-Chalumeau reported no relevant financial relationships apart from unrestricted institutional research grants from UCB and Roche.
AT LUPUS 2023
Full Resolution of Psoriasis in Half of Ixekizumab Patients
More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.
The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).
Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.
Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.
In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).
In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.
The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.
Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.
The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”
Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.
There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.
The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.
*A previous version of this article misstated the period during which three placebo patients received ixekizumab.
More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.
The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).
Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.
Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.
In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).
In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.
The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.
Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.
The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”
Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.
There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.
The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.
*A previous version of this article misstated the period during which three placebo patients received ixekizumab.
More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.
The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).
Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.
Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.
In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).
In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.
The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.
Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.
The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”
Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.
There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.
The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.
*A previous version of this article misstated the period during which three placebo patients received ixekizumab.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE