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Inflammatory arthritis induced by ICIs can persist after therapy
according to a new study of long-term outcomes of immune-related adverse events published in Annals of the Rheumatic Diseases.
“This study is one of the largest longitudinal reports to date of patients with ICI-induced IA and the first to evaluate persistence of ICI-induced IA and identify influential factors on outcome,” wrote Tawnie J. Braaten, MD, and coauthors. “Continued clinical and translational investigation on larger longitudinal cohorts will allow for increased understanding of pathophysiology and determination of the best clinical care for patients with ICI-induced IA.”
Dr. Braaten conducted the study at Johns Hopkins University, Baltimore, when she was a postdoctoral fellow there, and she is now in the division of rheumatology at the University of Utah, Salt Lake City.
To determine how long IA can persist after patients cease ICI therapy, along with factors associated with its persistence, the researchers studied 60 patients who were referred to the Johns Hopkins Arthritis Center for IA caused by ICIs. The patients – 32 females and 28 males – had a median follow-up of 9 months after ICI cessation.
Of the 51 patients with 3-month follow-up data, 70.6% had active IA. Of the 41 patients with 6-month follow-up data, 48.8% had active IA. All told, 53.3% of patients had active IA at their last follow-up visit, which occurred anywhere from 1 to 24 months after stopping ICI therapy.
According to univariable analysis, arthritis was less likely to improve in patients with a longer duration of ICI exposure (hazard ratio, 0.93; 95% confidence interval, 0.87-0.99; P = .02), in patients receiving combination ICI therapy (HR, 0.29; 95% CI, 0.12-0.72; P = .008) and in patients with a history of other immune-related adverse events (HR, 0.61; 95% CI, 0.39-0.95; P = .03).
The authors acknowledged their study’s limitations, including a potential selection bias for symptomatic individuals and the possibility that persistent IA sufferers may have pursued follow-up for longer periods of time. In addition, they noted that some patients were omitted from analysis if they were on a blinded clinical trial or had been receiving an investigational immunotherapy agent.
The study was funded via a grant from Bristol-Myers Squibb, an arthritis fellowship award from AbbVie, and additional financial support from the Camille Julia Morgan Arthritis Research and Education Fund, the Jerome L. Greene Foundation, and the National Institutes of Health. The authors reported various conflicts of interest, including receiving honoraria, grants, and research funding from numerous pharmaceutical companies.
SOURCE: Braaten TJ et al. Ann Rheum Dis. 2019 Sep 20. doi: 10.1136/annrheumdis-2019-216109.
according to a new study of long-term outcomes of immune-related adverse events published in Annals of the Rheumatic Diseases.
“This study is one of the largest longitudinal reports to date of patients with ICI-induced IA and the first to evaluate persistence of ICI-induced IA and identify influential factors on outcome,” wrote Tawnie J. Braaten, MD, and coauthors. “Continued clinical and translational investigation on larger longitudinal cohorts will allow for increased understanding of pathophysiology and determination of the best clinical care for patients with ICI-induced IA.”
Dr. Braaten conducted the study at Johns Hopkins University, Baltimore, when she was a postdoctoral fellow there, and she is now in the division of rheumatology at the University of Utah, Salt Lake City.
To determine how long IA can persist after patients cease ICI therapy, along with factors associated with its persistence, the researchers studied 60 patients who were referred to the Johns Hopkins Arthritis Center for IA caused by ICIs. The patients – 32 females and 28 males – had a median follow-up of 9 months after ICI cessation.
Of the 51 patients with 3-month follow-up data, 70.6% had active IA. Of the 41 patients with 6-month follow-up data, 48.8% had active IA. All told, 53.3% of patients had active IA at their last follow-up visit, which occurred anywhere from 1 to 24 months after stopping ICI therapy.
According to univariable analysis, arthritis was less likely to improve in patients with a longer duration of ICI exposure (hazard ratio, 0.93; 95% confidence interval, 0.87-0.99; P = .02), in patients receiving combination ICI therapy (HR, 0.29; 95% CI, 0.12-0.72; P = .008) and in patients with a history of other immune-related adverse events (HR, 0.61; 95% CI, 0.39-0.95; P = .03).
The authors acknowledged their study’s limitations, including a potential selection bias for symptomatic individuals and the possibility that persistent IA sufferers may have pursued follow-up for longer periods of time. In addition, they noted that some patients were omitted from analysis if they were on a blinded clinical trial or had been receiving an investigational immunotherapy agent.
The study was funded via a grant from Bristol-Myers Squibb, an arthritis fellowship award from AbbVie, and additional financial support from the Camille Julia Morgan Arthritis Research and Education Fund, the Jerome L. Greene Foundation, and the National Institutes of Health. The authors reported various conflicts of interest, including receiving honoraria, grants, and research funding from numerous pharmaceutical companies.
SOURCE: Braaten TJ et al. Ann Rheum Dis. 2019 Sep 20. doi: 10.1136/annrheumdis-2019-216109.
according to a new study of long-term outcomes of immune-related adverse events published in Annals of the Rheumatic Diseases.
“This study is one of the largest longitudinal reports to date of patients with ICI-induced IA and the first to evaluate persistence of ICI-induced IA and identify influential factors on outcome,” wrote Tawnie J. Braaten, MD, and coauthors. “Continued clinical and translational investigation on larger longitudinal cohorts will allow for increased understanding of pathophysiology and determination of the best clinical care for patients with ICI-induced IA.”
Dr. Braaten conducted the study at Johns Hopkins University, Baltimore, when she was a postdoctoral fellow there, and she is now in the division of rheumatology at the University of Utah, Salt Lake City.
To determine how long IA can persist after patients cease ICI therapy, along with factors associated with its persistence, the researchers studied 60 patients who were referred to the Johns Hopkins Arthritis Center for IA caused by ICIs. The patients – 32 females and 28 males – had a median follow-up of 9 months after ICI cessation.
Of the 51 patients with 3-month follow-up data, 70.6% had active IA. Of the 41 patients with 6-month follow-up data, 48.8% had active IA. All told, 53.3% of patients had active IA at their last follow-up visit, which occurred anywhere from 1 to 24 months after stopping ICI therapy.
According to univariable analysis, arthritis was less likely to improve in patients with a longer duration of ICI exposure (hazard ratio, 0.93; 95% confidence interval, 0.87-0.99; P = .02), in patients receiving combination ICI therapy (HR, 0.29; 95% CI, 0.12-0.72; P = .008) and in patients with a history of other immune-related adverse events (HR, 0.61; 95% CI, 0.39-0.95; P = .03).
The authors acknowledged their study’s limitations, including a potential selection bias for symptomatic individuals and the possibility that persistent IA sufferers may have pursued follow-up for longer periods of time. In addition, they noted that some patients were omitted from analysis if they were on a blinded clinical trial or had been receiving an investigational immunotherapy agent.
The study was funded via a grant from Bristol-Myers Squibb, an arthritis fellowship award from AbbVie, and additional financial support from the Camille Julia Morgan Arthritis Research and Education Fund, the Jerome L. Greene Foundation, and the National Institutes of Health. The authors reported various conflicts of interest, including receiving honoraria, grants, and research funding from numerous pharmaceutical companies.
SOURCE: Braaten TJ et al. Ann Rheum Dis. 2019 Sep 20. doi: 10.1136/annrheumdis-2019-216109.
FROM ANNALS OF THE RHEUMATIC DISEASES
TKI preserved lung function in patients with fibrosing interstitial disease
MADRID – according to findings from a phase 3, placebo-controlled trial presented at the annual congress of the European Respiratory Society.
The trial, called INBUILD, enrolled patients who had a progressive lung disease with a fibrosing phenotype, such as interstitial pneumonia with autoimmune features (IPAF) or noninterstitial pneumonia (NSIP), on the premise that these conditions might share a pathology responsive to a common therapy, explained Kevin R. Flaherty, MD, of National Jewish Health, Denver. The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at 153 sites in 15 countries. A total of 663 patients underwent randomization and received at least one dose of nintedanib (332) or placebo (331).
Patients with fibrosing lung disease affecting more than 10% of lung volume were randomized to 150 mg twice daily of nintedanib, which inhibits intracellular growth factors implicated in fibrosis and is already indicated for IPF, or matching placebo.
On the primary endpoint of change in forced vital capacity (FVC) at 52 weeks, those in the nintedanib arm lost lung function at a rate that was less than half that of those randomized to placebo (–80.8 vs. –187.8 mL/year; P less than .001).
In a preplanned stratification, the protection from nintedanib against a decline in lung function was found to be at least as good in those with a usual interstitial pneumonia (UIP-like) pattern of fibrosis on baseline imaging (–82.9 vs. –211.1 mL/year), compared with those with other fibrotic patterns (–79.0 vs. –154.2 mL/year). The UIP-like subgroup represented about 60% of those enrolled.
“The relative protection from decline in lung function supports the hypothesis that progressive fibrosing interstitial lung diseases have a similar pathobiologic mechanism,” said Dr. Flaherty. Results from the INBUILD were published simultaneously with his ERS presentation (N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681).
The curves documenting change of lung function in favor of nintedanib relative to placebo separated within 12 weeks of treatment initiation, according to Dr. Flaherty. The ERS-invited discussant, Martin Kolb, MD, PhD, professor of respirology, McMaster University, Hamilton, Ont., called the reductions in loss of lung function “profound” and “very impactful.”
However, despite these reductions, there was no significant difference in quality of life as measured with the King’s Brief Interstitial Lung Disease (KBILD) questionnaire, which was a secondary outcome. The problem was that there was little change in KBILD in either group at 52 weeks, limiting the ability to show differences.
The rates of death were numerically lower at 52 weeks in the nintedanib arm for the study overall (4.8% vs. 5.1%) and for the UIP-like subgroup (5.3% vs. 7.8%), but the differences did not reach statistical significance.
A suggestion of benefit was derived from a design feature of INBUILD that called for patients to remain on blinded therapy until all enrolled patients completed the trial. When the effect of nintedanib was evaluated in this extended analysis, the event curves for the combined endpoint of interstitial lung disease or death separated and approached significance.
In this extended analysis, which suggests that clinical benefit is likely to accrue after longer periods of treatment, “we saw similar trends when we looked at mortality as an independent outcome,” Dr. Flaherty reported.
More patients in the nintedanib group discontinued therapy because of adverse events (19.6% vs. 10.3%), but Dr. Flaherty characterized the rate of serious adverse events as “similar.” He made this statement even though several adverse events, particularly those involving the gastrointestinal tract, such as diarrhea (66.9% vs. 23.9%), nausea (28.9% vs. 9.4%), vomiting (18.4% vs. 5.1%), and abdominal pain (10.2% vs. 2.4%), were higher in the nintedanib arm.
The INBUILD trial demonstrates that nintedanib preserves lung function in fibrosing lung diseases other than IPF. In his review of this paper, Dr. Kolb pointed out that non-IPF etiologies represent about 75% of interstitial lung diseases. For these patients “we have no drugs, so there is a big medical need.”
Dr. Flaherty reports no potential conflicts of interest. The study was funded by Boehringer-Ingelheim, which produces nintedanib.
SOURCE: Flaherty KR et al. N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681.
MADRID – according to findings from a phase 3, placebo-controlled trial presented at the annual congress of the European Respiratory Society.
The trial, called INBUILD, enrolled patients who had a progressive lung disease with a fibrosing phenotype, such as interstitial pneumonia with autoimmune features (IPAF) or noninterstitial pneumonia (NSIP), on the premise that these conditions might share a pathology responsive to a common therapy, explained Kevin R. Flaherty, MD, of National Jewish Health, Denver. The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at 153 sites in 15 countries. A total of 663 patients underwent randomization and received at least one dose of nintedanib (332) or placebo (331).
Patients with fibrosing lung disease affecting more than 10% of lung volume were randomized to 150 mg twice daily of nintedanib, which inhibits intracellular growth factors implicated in fibrosis and is already indicated for IPF, or matching placebo.
On the primary endpoint of change in forced vital capacity (FVC) at 52 weeks, those in the nintedanib arm lost lung function at a rate that was less than half that of those randomized to placebo (–80.8 vs. –187.8 mL/year; P less than .001).
In a preplanned stratification, the protection from nintedanib against a decline in lung function was found to be at least as good in those with a usual interstitial pneumonia (UIP-like) pattern of fibrosis on baseline imaging (–82.9 vs. –211.1 mL/year), compared with those with other fibrotic patterns (–79.0 vs. –154.2 mL/year). The UIP-like subgroup represented about 60% of those enrolled.
“The relative protection from decline in lung function supports the hypothesis that progressive fibrosing interstitial lung diseases have a similar pathobiologic mechanism,” said Dr. Flaherty. Results from the INBUILD were published simultaneously with his ERS presentation (N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681).
The curves documenting change of lung function in favor of nintedanib relative to placebo separated within 12 weeks of treatment initiation, according to Dr. Flaherty. The ERS-invited discussant, Martin Kolb, MD, PhD, professor of respirology, McMaster University, Hamilton, Ont., called the reductions in loss of lung function “profound” and “very impactful.”
However, despite these reductions, there was no significant difference in quality of life as measured with the King’s Brief Interstitial Lung Disease (KBILD) questionnaire, which was a secondary outcome. The problem was that there was little change in KBILD in either group at 52 weeks, limiting the ability to show differences.
The rates of death were numerically lower at 52 weeks in the nintedanib arm for the study overall (4.8% vs. 5.1%) and for the UIP-like subgroup (5.3% vs. 7.8%), but the differences did not reach statistical significance.
A suggestion of benefit was derived from a design feature of INBUILD that called for patients to remain on blinded therapy until all enrolled patients completed the trial. When the effect of nintedanib was evaluated in this extended analysis, the event curves for the combined endpoint of interstitial lung disease or death separated and approached significance.
In this extended analysis, which suggests that clinical benefit is likely to accrue after longer periods of treatment, “we saw similar trends when we looked at mortality as an independent outcome,” Dr. Flaherty reported.
More patients in the nintedanib group discontinued therapy because of adverse events (19.6% vs. 10.3%), but Dr. Flaherty characterized the rate of serious adverse events as “similar.” He made this statement even though several adverse events, particularly those involving the gastrointestinal tract, such as diarrhea (66.9% vs. 23.9%), nausea (28.9% vs. 9.4%), vomiting (18.4% vs. 5.1%), and abdominal pain (10.2% vs. 2.4%), were higher in the nintedanib arm.
The INBUILD trial demonstrates that nintedanib preserves lung function in fibrosing lung diseases other than IPF. In his review of this paper, Dr. Kolb pointed out that non-IPF etiologies represent about 75% of interstitial lung diseases. For these patients “we have no drugs, so there is a big medical need.”
Dr. Flaherty reports no potential conflicts of interest. The study was funded by Boehringer-Ingelheim, which produces nintedanib.
SOURCE: Flaherty KR et al. N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681.
MADRID – according to findings from a phase 3, placebo-controlled trial presented at the annual congress of the European Respiratory Society.
The trial, called INBUILD, enrolled patients who had a progressive lung disease with a fibrosing phenotype, such as interstitial pneumonia with autoimmune features (IPAF) or noninterstitial pneumonia (NSIP), on the premise that these conditions might share a pathology responsive to a common therapy, explained Kevin R. Flaherty, MD, of National Jewish Health, Denver. The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at 153 sites in 15 countries. A total of 663 patients underwent randomization and received at least one dose of nintedanib (332) or placebo (331).
Patients with fibrosing lung disease affecting more than 10% of lung volume were randomized to 150 mg twice daily of nintedanib, which inhibits intracellular growth factors implicated in fibrosis and is already indicated for IPF, or matching placebo.
On the primary endpoint of change in forced vital capacity (FVC) at 52 weeks, those in the nintedanib arm lost lung function at a rate that was less than half that of those randomized to placebo (–80.8 vs. –187.8 mL/year; P less than .001).
In a preplanned stratification, the protection from nintedanib against a decline in lung function was found to be at least as good in those with a usual interstitial pneumonia (UIP-like) pattern of fibrosis on baseline imaging (–82.9 vs. –211.1 mL/year), compared with those with other fibrotic patterns (–79.0 vs. –154.2 mL/year). The UIP-like subgroup represented about 60% of those enrolled.
“The relative protection from decline in lung function supports the hypothesis that progressive fibrosing interstitial lung diseases have a similar pathobiologic mechanism,” said Dr. Flaherty. Results from the INBUILD were published simultaneously with his ERS presentation (N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681).
The curves documenting change of lung function in favor of nintedanib relative to placebo separated within 12 weeks of treatment initiation, according to Dr. Flaherty. The ERS-invited discussant, Martin Kolb, MD, PhD, professor of respirology, McMaster University, Hamilton, Ont., called the reductions in loss of lung function “profound” and “very impactful.”
However, despite these reductions, there was no significant difference in quality of life as measured with the King’s Brief Interstitial Lung Disease (KBILD) questionnaire, which was a secondary outcome. The problem was that there was little change in KBILD in either group at 52 weeks, limiting the ability to show differences.
The rates of death were numerically lower at 52 weeks in the nintedanib arm for the study overall (4.8% vs. 5.1%) and for the UIP-like subgroup (5.3% vs. 7.8%), but the differences did not reach statistical significance.
A suggestion of benefit was derived from a design feature of INBUILD that called for patients to remain on blinded therapy until all enrolled patients completed the trial. When the effect of nintedanib was evaluated in this extended analysis, the event curves for the combined endpoint of interstitial lung disease or death separated and approached significance.
In this extended analysis, which suggests that clinical benefit is likely to accrue after longer periods of treatment, “we saw similar trends when we looked at mortality as an independent outcome,” Dr. Flaherty reported.
More patients in the nintedanib group discontinued therapy because of adverse events (19.6% vs. 10.3%), but Dr. Flaherty characterized the rate of serious adverse events as “similar.” He made this statement even though several adverse events, particularly those involving the gastrointestinal tract, such as diarrhea (66.9% vs. 23.9%), nausea (28.9% vs. 9.4%), vomiting (18.4% vs. 5.1%), and abdominal pain (10.2% vs. 2.4%), were higher in the nintedanib arm.
The INBUILD trial demonstrates that nintedanib preserves lung function in fibrosing lung diseases other than IPF. In his review of this paper, Dr. Kolb pointed out that non-IPF etiologies represent about 75% of interstitial lung diseases. For these patients “we have no drugs, so there is a big medical need.”
Dr. Flaherty reports no potential conflicts of interest. The study was funded by Boehringer-Ingelheim, which produces nintedanib.
SOURCE: Flaherty KR et al. N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681.
REPORTING FROM ERS 2019
FDA approves rituximab to treat children with rare vasculitis
The Food and Drug Administration approved rituximab (Rituxan) by injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoid treatment, according to an FDA news release.
These rare forms of vasculitis damage small blood vessels through inflammation and can lead to serious organ failure, including lungs and kidneys.
The Genentech drug received priority review and an orphan drug designation based on the results of a pediatric clinical trial of 25 patients aged 6-17 years with active GPA or MPA who were treated with rituximab in an international multicenter, open-label, uncontrolled study. Patients in the trial were also given methylprednisolone prior to starting treatment.
The trial consisted of a 6-month remission induction phase where patients were treated only with rituximab and glucocorticoids. In addition, patients who had not achieved remission could receive additional treatment, including other therapies, at the discretion of the investigator, according to the FDA. By 6 months, 14 of the patients were in remission, and after 18 months, all 25 patients were in remission.
Rituximab contains a boxed warning regarding increased risks of fatal infusion reactions, potentially fatal severe skin and mouth reactions, hepatitis B virus reactivation that may cause serious or lethal liver problems, and progressive multifocal leukoencephalopathy, a rare, potentially lethal brain infection.
The trial was conducted and sponsored by F. Hoffmann-La Roche, which owns Genentech.
The Food and Drug Administration approved rituximab (Rituxan) by injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoid treatment, according to an FDA news release.
These rare forms of vasculitis damage small blood vessels through inflammation and can lead to serious organ failure, including lungs and kidneys.
The Genentech drug received priority review and an orphan drug designation based on the results of a pediatric clinical trial of 25 patients aged 6-17 years with active GPA or MPA who were treated with rituximab in an international multicenter, open-label, uncontrolled study. Patients in the trial were also given methylprednisolone prior to starting treatment.
The trial consisted of a 6-month remission induction phase where patients were treated only with rituximab and glucocorticoids. In addition, patients who had not achieved remission could receive additional treatment, including other therapies, at the discretion of the investigator, according to the FDA. By 6 months, 14 of the patients were in remission, and after 18 months, all 25 patients were in remission.
Rituximab contains a boxed warning regarding increased risks of fatal infusion reactions, potentially fatal severe skin and mouth reactions, hepatitis B virus reactivation that may cause serious or lethal liver problems, and progressive multifocal leukoencephalopathy, a rare, potentially lethal brain infection.
The trial was conducted and sponsored by F. Hoffmann-La Roche, which owns Genentech.
The Food and Drug Administration approved rituximab (Rituxan) by injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoid treatment, according to an FDA news release.
These rare forms of vasculitis damage small blood vessels through inflammation and can lead to serious organ failure, including lungs and kidneys.
The Genentech drug received priority review and an orphan drug designation based on the results of a pediatric clinical trial of 25 patients aged 6-17 years with active GPA or MPA who were treated with rituximab in an international multicenter, open-label, uncontrolled study. Patients in the trial were also given methylprednisolone prior to starting treatment.
The trial consisted of a 6-month remission induction phase where patients were treated only with rituximab and glucocorticoids. In addition, patients who had not achieved remission could receive additional treatment, including other therapies, at the discretion of the investigator, according to the FDA. By 6 months, 14 of the patients were in remission, and after 18 months, all 25 patients were in remission.
Rituximab contains a boxed warning regarding increased risks of fatal infusion reactions, potentially fatal severe skin and mouth reactions, hepatitis B virus reactivation that may cause serious or lethal liver problems, and progressive multifocal leukoencephalopathy, a rare, potentially lethal brain infection.
The trial was conducted and sponsored by F. Hoffmann-La Roche, which owns Genentech.
Zostavax proves safe, effective in patients with nonactive SLE
A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.
A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.
Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.
After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.
“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.
In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.
The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.
However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.
None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.
The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.
“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.
But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.
The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.
SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925
Probably like me you have seen a bit of zoster in our patients with SLE, and rarely we get severe outbreaks in multiple dermatomes or in the eyes or other vulnerable areas in patients on immune suppression. So I think of Zostavax the way I think of shingles per se: The more immune compromised you are, the higher the risk of something bad happening … maybe. But we do know with Zostavax the risk is small.
Shingrix is a lot more effective than Zostavax and does not have the same issue of potentially causing the thing it prevents. But the most likely reason it works so well is that it has an adjuvant. We are generally a lot more concerned about injecting adjuvants in autoimmune patients here in the United States than they are in Europe where they have more experience with that, but this one is apparently a new adjuvant and has never been used in autoimmune patients, who were excluded from the trials of Shingrix. And a fair number of nonautoimmune patients get autoimmune-like symptoms in the Shingrix trials such as myalgias and fevers. I don’t think we have full confidence yet until we figure out just how worried we ought to be about that. In other words, if Shingrix only causes mild/moderate transient flares, then our patients might rationally consider that a fair trade for lifelong protection.
I think in some patients this is an easier decision than others. If somebody is 50 years old and healthy, hasn’t had nephritis or anything bad before (or not in the last 10 years), and is on no immune suppressant or just using stable, modest doses of such therapies, you would probably recommend doing something to avoid getting zoster. And here you can explain the choice to the patient: Zostavax provides good protection but less than Shingrix, is unlikely to make the patient flare, has very low risk of live vaccine causing much trouble in a generally healthy person; Shingrix is more effective overall, has caused some autoimmune symptoms in healthy people, and has unclear risk for a flare in a patient with a diagnosis (but that can be monitored).
For the sicker patients, we just have to weigh the risk of a natural zoster outbreak against the risk of a flare and the risk of disseminated zoster from the Zostavax, which is a pretty small risk but it is there. It’s a discussion you need to have in advance with each patient. Maybe with some patients, it is best to wait for an optimal time for either choice, when there’s not too much disease and not too much immune-compromising medication.
An unsolved issue for herpes zoster vaccination is age. Greater knowledge about how to best vaccinate would go a long way toward bolstering confidence in using the vaccines in patients a bit younger than 50 years given that zoster does occur in lupus patients at that age.
Joan Merrill, MD, is OMRF Professor of Medicine at the University of Oklahoma Health Sciences Center and a member of the Arthritis & Clinical Immunology Research Program at the Oklahoma Medical Research Foundation, both in Oklahoma City. She is a member of the editorial advisory board of Rheumatology News.
Probably like me you have seen a bit of zoster in our patients with SLE, and rarely we get severe outbreaks in multiple dermatomes or in the eyes or other vulnerable areas in patients on immune suppression. So I think of Zostavax the way I think of shingles per se: The more immune compromised you are, the higher the risk of something bad happening … maybe. But we do know with Zostavax the risk is small.
Shingrix is a lot more effective than Zostavax and does not have the same issue of potentially causing the thing it prevents. But the most likely reason it works so well is that it has an adjuvant. We are generally a lot more concerned about injecting adjuvants in autoimmune patients here in the United States than they are in Europe where they have more experience with that, but this one is apparently a new adjuvant and has never been used in autoimmune patients, who were excluded from the trials of Shingrix. And a fair number of nonautoimmune patients get autoimmune-like symptoms in the Shingrix trials such as myalgias and fevers. I don’t think we have full confidence yet until we figure out just how worried we ought to be about that. In other words, if Shingrix only causes mild/moderate transient flares, then our patients might rationally consider that a fair trade for lifelong protection.
I think in some patients this is an easier decision than others. If somebody is 50 years old and healthy, hasn’t had nephritis or anything bad before (or not in the last 10 years), and is on no immune suppressant or just using stable, modest doses of such therapies, you would probably recommend doing something to avoid getting zoster. And here you can explain the choice to the patient: Zostavax provides good protection but less than Shingrix, is unlikely to make the patient flare, has very low risk of live vaccine causing much trouble in a generally healthy person; Shingrix is more effective overall, has caused some autoimmune symptoms in healthy people, and has unclear risk for a flare in a patient with a diagnosis (but that can be monitored).
For the sicker patients, we just have to weigh the risk of a natural zoster outbreak against the risk of a flare and the risk of disseminated zoster from the Zostavax, which is a pretty small risk but it is there. It’s a discussion you need to have in advance with each patient. Maybe with some patients, it is best to wait for an optimal time for either choice, when there’s not too much disease and not too much immune-compromising medication.
An unsolved issue for herpes zoster vaccination is age. Greater knowledge about how to best vaccinate would go a long way toward bolstering confidence in using the vaccines in patients a bit younger than 50 years given that zoster does occur in lupus patients at that age.
Joan Merrill, MD, is OMRF Professor of Medicine at the University of Oklahoma Health Sciences Center and a member of the Arthritis & Clinical Immunology Research Program at the Oklahoma Medical Research Foundation, both in Oklahoma City. She is a member of the editorial advisory board of Rheumatology News.
Probably like me you have seen a bit of zoster in our patients with SLE, and rarely we get severe outbreaks in multiple dermatomes or in the eyes or other vulnerable areas in patients on immune suppression. So I think of Zostavax the way I think of shingles per se: The more immune compromised you are, the higher the risk of something bad happening … maybe. But we do know with Zostavax the risk is small.
Shingrix is a lot more effective than Zostavax and does not have the same issue of potentially causing the thing it prevents. But the most likely reason it works so well is that it has an adjuvant. We are generally a lot more concerned about injecting adjuvants in autoimmune patients here in the United States than they are in Europe where they have more experience with that, but this one is apparently a new adjuvant and has never been used in autoimmune patients, who were excluded from the trials of Shingrix. And a fair number of nonautoimmune patients get autoimmune-like symptoms in the Shingrix trials such as myalgias and fevers. I don’t think we have full confidence yet until we figure out just how worried we ought to be about that. In other words, if Shingrix only causes mild/moderate transient flares, then our patients might rationally consider that a fair trade for lifelong protection.
I think in some patients this is an easier decision than others. If somebody is 50 years old and healthy, hasn’t had nephritis or anything bad before (or not in the last 10 years), and is on no immune suppressant or just using stable, modest doses of such therapies, you would probably recommend doing something to avoid getting zoster. And here you can explain the choice to the patient: Zostavax provides good protection but less than Shingrix, is unlikely to make the patient flare, has very low risk of live vaccine causing much trouble in a generally healthy person; Shingrix is more effective overall, has caused some autoimmune symptoms in healthy people, and has unclear risk for a flare in a patient with a diagnosis (but that can be monitored).
For the sicker patients, we just have to weigh the risk of a natural zoster outbreak against the risk of a flare and the risk of disseminated zoster from the Zostavax, which is a pretty small risk but it is there. It’s a discussion you need to have in advance with each patient. Maybe with some patients, it is best to wait for an optimal time for either choice, when there’s not too much disease and not too much immune-compromising medication.
An unsolved issue for herpes zoster vaccination is age. Greater knowledge about how to best vaccinate would go a long way toward bolstering confidence in using the vaccines in patients a bit younger than 50 years given that zoster does occur in lupus patients at that age.
Joan Merrill, MD, is OMRF Professor of Medicine at the University of Oklahoma Health Sciences Center and a member of the Arthritis & Clinical Immunology Research Program at the Oklahoma Medical Research Foundation, both in Oklahoma City. She is a member of the editorial advisory board of Rheumatology News.
A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.
A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.
Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.
After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.
“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.
In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.
The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.
However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.
None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.
The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.
“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.
But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.
The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.
SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925
A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.
A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.
Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.
After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.
“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.
In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.
The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.
However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.
None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.
The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.
“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.
But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.
The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.
SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925
FROM ANNALS OF THE RHEUMATIC DISEASES
Prior authorizations for infusibles cause delays, toxicities
Rheumatologist Zachary S. Wallace, MD, knew just how prior authorization requirements were impacting his staff time and work flow when he embarked on a study several years ago. Managing authorizations for infusible medications alone was about to become a full-time job for one of the administrative assistants in the rheumatology unit at Massachusetts General Hospital in Boston.
His research questions concerned patients. “There’s a lot of talk about how much onus prior authorization requirements put on providers and the practice,” Dr. Wallace said. ”I was interested in understanding what impact [these requirements] have on patients themselves.”
Dr. Wallace led a review of the EHRs of 225 patients for whom an infusible medication such as rituximab and infliximab was ordered by 1 of the 16 physicians in the rheumatology unit between July 2016 and June 2018. The findings – that patients who needed prior authorizations for infusible medications had a significantly longer time to treatment initiation and higher prednisone-equivalent glucocorticoid exposure – were reported online in Arthritis Care & Research.
Among patients whose authorizations were initially denied, these differences were “pretty drastic,” Dr. Wallace said. The median time to receiving a first infusion was 50 days, compared with 27 days when permission was not required, and glucocorticoid exposure during the 3 months following the request was 605 mg versus 160 mg.
Among patients whose authorizations were not denied, the median time to first infusion was 31 days, compared with 27 days when authorization was not required, and the mean glucocorticoid exposure over 3 months was 364 mg versus 160 mg.
“I hope that our findings will help facilitate discussions with insurance providers, pharmacy benefit managers, and state and federal legislators about the need to address the impact that prior authorization requirements have on patients and providers,” said Dr. Wallace, also of the clinical epidemiology program in the division of rheumatology, allergy and immunology at Massachusetts General, and an assistant professor of medicine at Harvard Medical School, Boston.
Of the 225 patients for whom an infusible medication was ordered, 71% required preauthorization. Of these, 79% were approved and 21% were denied after the first request. And in a finding that Dr. Wallace called “somewhat surprising,” 82% of the authorizations originally denied were approved after appeal.
All told, prior authorizations for infusible medications were eventually approved in all but a small number of cases. “We go through all this effort to get these prior authorizations approved, and 96% of the time, they were ultimately approved,” he said in an interview.
Christopher Phillips, MD, a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the American College of Rheumatology’s committee on rheumatologic care, said the findings “give further credence” to rheumatologists’ concerns. “We know [from our own experiences] that prior authorizations delay care, and we know that delays can cause harm to patients. We now have hard data backing up this assertion.”
Regarding the high number of authorization approvals, “there’s an argument to be made that for certain treatments and certain conditions where the success rate of appeals is high enough, you shouldn’t be subjecting these treatments to these [preauthorization] policies,” he said.
Calls for prior authorization reform
Most patients in the study (71%) had private insurance. But the findings also have implications for Medicare, Dr. Wallace said, as recent federal policies have expanded Medicare Advantage plans’ authority to use prior authorization in conjunction with step therapy for medications administered under Part B. Step therapy favors primary use of what insurers deem the most cost-effective therapies.
The ACR is one of almost 370 physician, patient, and health care organizations that are urging Congress to pass a bipartisan bill aimed at streamlining and standardizing prior authorization under the Medicare Advantage program. The legislation – Improving Seniors’ Timely Access to Care Act of 2019 (H.R. 3107) – was introduced by Reps. Suzan DelBene (D-Wash.), Mike Kelly (R-Pa.), Roger Marshall, MD (R-Kan.), and Ami Bera, MD (D-Calif.).
The bill calls for the creation of an electronic prior authorization program and a “real-time process for items and services that are routinely approved,” as well as greater Centers for Medicare & Medicaid Services oversight on how Medicare Advantage plans use prior authorization. Plans would be required to report to the CMS on the extent of their use of prior authorization and the rate of approvals or denials. They would also be held accountable for making timely prior authorization determinations and providing rationales for denials, according to a letter to Congress cosigned by the ACR.
In a press release about the legislation, Paula Marchetta, MD, president of the ACR, said that “the unregulated use of prior authorization has devolved into a time-consuming and obstructive process that often stalls or outright revokes patient access to medically necessary therapies.” She added that “many health care plans now use prior authorization indiscriminately.”
Cathryn Donaldson, director of communications for America’s Health Insurance Plans (AHIP), said in an email that prior authorization is used for less than 15% of covered services, and that, along with step therapy, it “helps ensure that patients receive care that is safe, effective, and necessary.” AHIP “knows that prior authorization can be improved,” she said, and is committed to streamlining the process.
A demonstration project on the automation of various parts of prior authorization is being coordinated with health information technology companies, plans, and providers, she noted.
The federal legislation is based at least partly on a consensus statement drafted by AHIP, the American Medical Association, and four other organizations representing hospitals, medical groups, and health plans on ways to improve the prior authorization process. Among the items mentioned in the statement is that “regular review” of services subject to prior authorization could help identify therapies that “no longer warrant” prior authorization because of low denial rates.
Outside of Medicare Advantage, the AMA is aware of at least 85 bills being introduced in states this year that address utilization management in commercial plans. Nearly all these bills attempt to reform prior authorization programs in some way, according to R. J. Mills, media relations coordinator for the AMA.
Rheumatologic patients hard hit
Off-label medication use was the most common reason (82%) for a prior authorization denial in the Massachusetts General study, even though 78% of the patients for whom infusible medications were prescribed had a condition with no Food and Drug Administration–approved treatment. Having such a condition was associated with 120% or 190% higher odds of having a denial in unadjusted and adjusted (for age and sex) analyses, Dr. Wallace and colleagues reported.
Moreover, nearly half (48%) of the patients with denials had already tried or were currently taking an oral disease-modifying antirheumatic drug, such as methotrexate.
The majority of denials were for the use of rituximab (70%), followed by infliximab (12%) and tocilizumab (12%). Most of the denials (79%) were appealed successfully through a peer-to-peer discussion. In five cases, the insurer’s preferred drug (for example, adalimumab) had to be used rather than the requested infusion (for example, infliximab).
Infused medications, many of which are biologics, are among the most expensive drugs prescribed for patients with rheumatic diseases. They were easiest for Dr. Wallace to study because of the way prior authorizations are handled in his unit, but prior authorization requirements are “widespread” in rheumatology practices across treatment types, he and Dr. Phillips said.
“Some of our relatively inexpensive treatments are subject to prior authorization requirements,” Dr. Phillips said. “We hear stories about prednisone needing a prior authorization sometimes.”
With respect to infusible medications, the insurance subcommittee is hearing from ACR members about seemingly increasing numbers of both clinical coverage reviews – for example, reviews of prior treatments – and site-of-care restrictions, Dr. Phillips noted. “Some carriers are insisting on infusions in non-hospital-based settings, for cost savings, or on home infusions, which are concerning because of [possible] infusion reactions and medical service availability.”
The application of step therapy to rheumatologic patients is troubling because of the “often unique medical circumstances of the patient,” Dr. Phillips said. “There are enough differences among the [tumor necrosis factor] antagonists, for instance, that make one more appropriate for a certain patient than another. Those differences are not brought into consideration with these policies.”
There are other ways in which prior authorization processes “are not well informed medically,” he said, recalling a case brought to the attention of the subcommittee in which a patient prescribed a biologic drug for psoriatic arthritis was denied authorization because “the documentation did not include a [disease activity measure] that is specific to RA and not used for psoriatic arthritis.”
It is not uncommon for authorizations for infusible medications to take 2 weeks or longer to secure – even when initially approved. In the AMA’s 2018 Prior Authorization Physician Survey, 65% reported waiting at least 1 business day for a decision and 26% reported waiting at least 3 business days for responses. “With infusibles, we’re absolutely dealing with a much longer time,” Dr. Phillips said.
In Dr. Wallace’s study, the finding that prior authorizations facilitated greater prednisone-equivalent glucocorticoid exposure is important, he and his colleagues wrote, because these medications may put patients at higher risk of infection, cardiovascular disease, and diabetes – even in low doses and with short-term use. Notably, the median delay to the initiation of treatment was 29 days, regardless of prior authorization requirements. Dr. Wallace said the delays “likely reflect a combination of factors” – including infusion center waiting lists and patient-level factors – and that his team is “thinking about how to facilitate better access [to their practice’s infusion center] for those who are approved for treatment.”
The most common conditions for which infused medication was ordered were inflammatory arthritis (32%), vasculitis (23%), and IgG4-related disease (17%). The 225 patients in the study had an average age of 53 years.
Dr. Wallace reported that he has no relevant financial disclosures.
SOURCE: Wallace ZS et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24062.
Rheumatologist Zachary S. Wallace, MD, knew just how prior authorization requirements were impacting his staff time and work flow when he embarked on a study several years ago. Managing authorizations for infusible medications alone was about to become a full-time job for one of the administrative assistants in the rheumatology unit at Massachusetts General Hospital in Boston.
His research questions concerned patients. “There’s a lot of talk about how much onus prior authorization requirements put on providers and the practice,” Dr. Wallace said. ”I was interested in understanding what impact [these requirements] have on patients themselves.”
Dr. Wallace led a review of the EHRs of 225 patients for whom an infusible medication such as rituximab and infliximab was ordered by 1 of the 16 physicians in the rheumatology unit between July 2016 and June 2018. The findings – that patients who needed prior authorizations for infusible medications had a significantly longer time to treatment initiation and higher prednisone-equivalent glucocorticoid exposure – were reported online in Arthritis Care & Research.
Among patients whose authorizations were initially denied, these differences were “pretty drastic,” Dr. Wallace said. The median time to receiving a first infusion was 50 days, compared with 27 days when permission was not required, and glucocorticoid exposure during the 3 months following the request was 605 mg versus 160 mg.
Among patients whose authorizations were not denied, the median time to first infusion was 31 days, compared with 27 days when authorization was not required, and the mean glucocorticoid exposure over 3 months was 364 mg versus 160 mg.
“I hope that our findings will help facilitate discussions with insurance providers, pharmacy benefit managers, and state and federal legislators about the need to address the impact that prior authorization requirements have on patients and providers,” said Dr. Wallace, also of the clinical epidemiology program in the division of rheumatology, allergy and immunology at Massachusetts General, and an assistant professor of medicine at Harvard Medical School, Boston.
Of the 225 patients for whom an infusible medication was ordered, 71% required preauthorization. Of these, 79% were approved and 21% were denied after the first request. And in a finding that Dr. Wallace called “somewhat surprising,” 82% of the authorizations originally denied were approved after appeal.
All told, prior authorizations for infusible medications were eventually approved in all but a small number of cases. “We go through all this effort to get these prior authorizations approved, and 96% of the time, they were ultimately approved,” he said in an interview.
Christopher Phillips, MD, a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the American College of Rheumatology’s committee on rheumatologic care, said the findings “give further credence” to rheumatologists’ concerns. “We know [from our own experiences] that prior authorizations delay care, and we know that delays can cause harm to patients. We now have hard data backing up this assertion.”
Regarding the high number of authorization approvals, “there’s an argument to be made that for certain treatments and certain conditions where the success rate of appeals is high enough, you shouldn’t be subjecting these treatments to these [preauthorization] policies,” he said.
Calls for prior authorization reform
Most patients in the study (71%) had private insurance. But the findings also have implications for Medicare, Dr. Wallace said, as recent federal policies have expanded Medicare Advantage plans’ authority to use prior authorization in conjunction with step therapy for medications administered under Part B. Step therapy favors primary use of what insurers deem the most cost-effective therapies.
The ACR is one of almost 370 physician, patient, and health care organizations that are urging Congress to pass a bipartisan bill aimed at streamlining and standardizing prior authorization under the Medicare Advantage program. The legislation – Improving Seniors’ Timely Access to Care Act of 2019 (H.R. 3107) – was introduced by Reps. Suzan DelBene (D-Wash.), Mike Kelly (R-Pa.), Roger Marshall, MD (R-Kan.), and Ami Bera, MD (D-Calif.).
The bill calls for the creation of an electronic prior authorization program and a “real-time process for items and services that are routinely approved,” as well as greater Centers for Medicare & Medicaid Services oversight on how Medicare Advantage plans use prior authorization. Plans would be required to report to the CMS on the extent of their use of prior authorization and the rate of approvals or denials. They would also be held accountable for making timely prior authorization determinations and providing rationales for denials, according to a letter to Congress cosigned by the ACR.
In a press release about the legislation, Paula Marchetta, MD, president of the ACR, said that “the unregulated use of prior authorization has devolved into a time-consuming and obstructive process that often stalls or outright revokes patient access to medically necessary therapies.” She added that “many health care plans now use prior authorization indiscriminately.”
Cathryn Donaldson, director of communications for America’s Health Insurance Plans (AHIP), said in an email that prior authorization is used for less than 15% of covered services, and that, along with step therapy, it “helps ensure that patients receive care that is safe, effective, and necessary.” AHIP “knows that prior authorization can be improved,” she said, and is committed to streamlining the process.
A demonstration project on the automation of various parts of prior authorization is being coordinated with health information technology companies, plans, and providers, she noted.
The federal legislation is based at least partly on a consensus statement drafted by AHIP, the American Medical Association, and four other organizations representing hospitals, medical groups, and health plans on ways to improve the prior authorization process. Among the items mentioned in the statement is that “regular review” of services subject to prior authorization could help identify therapies that “no longer warrant” prior authorization because of low denial rates.
Outside of Medicare Advantage, the AMA is aware of at least 85 bills being introduced in states this year that address utilization management in commercial plans. Nearly all these bills attempt to reform prior authorization programs in some way, according to R. J. Mills, media relations coordinator for the AMA.
Rheumatologic patients hard hit
Off-label medication use was the most common reason (82%) for a prior authorization denial in the Massachusetts General study, even though 78% of the patients for whom infusible medications were prescribed had a condition with no Food and Drug Administration–approved treatment. Having such a condition was associated with 120% or 190% higher odds of having a denial in unadjusted and adjusted (for age and sex) analyses, Dr. Wallace and colleagues reported.
Moreover, nearly half (48%) of the patients with denials had already tried or were currently taking an oral disease-modifying antirheumatic drug, such as methotrexate.
The majority of denials were for the use of rituximab (70%), followed by infliximab (12%) and tocilizumab (12%). Most of the denials (79%) were appealed successfully through a peer-to-peer discussion. In five cases, the insurer’s preferred drug (for example, adalimumab) had to be used rather than the requested infusion (for example, infliximab).
Infused medications, many of which are biologics, are among the most expensive drugs prescribed for patients with rheumatic diseases. They were easiest for Dr. Wallace to study because of the way prior authorizations are handled in his unit, but prior authorization requirements are “widespread” in rheumatology practices across treatment types, he and Dr. Phillips said.
“Some of our relatively inexpensive treatments are subject to prior authorization requirements,” Dr. Phillips said. “We hear stories about prednisone needing a prior authorization sometimes.”
With respect to infusible medications, the insurance subcommittee is hearing from ACR members about seemingly increasing numbers of both clinical coverage reviews – for example, reviews of prior treatments – and site-of-care restrictions, Dr. Phillips noted. “Some carriers are insisting on infusions in non-hospital-based settings, for cost savings, or on home infusions, which are concerning because of [possible] infusion reactions and medical service availability.”
The application of step therapy to rheumatologic patients is troubling because of the “often unique medical circumstances of the patient,” Dr. Phillips said. “There are enough differences among the [tumor necrosis factor] antagonists, for instance, that make one more appropriate for a certain patient than another. Those differences are not brought into consideration with these policies.”
There are other ways in which prior authorization processes “are not well informed medically,” he said, recalling a case brought to the attention of the subcommittee in which a patient prescribed a biologic drug for psoriatic arthritis was denied authorization because “the documentation did not include a [disease activity measure] that is specific to RA and not used for psoriatic arthritis.”
It is not uncommon for authorizations for infusible medications to take 2 weeks or longer to secure – even when initially approved. In the AMA’s 2018 Prior Authorization Physician Survey, 65% reported waiting at least 1 business day for a decision and 26% reported waiting at least 3 business days for responses. “With infusibles, we’re absolutely dealing with a much longer time,” Dr. Phillips said.
In Dr. Wallace’s study, the finding that prior authorizations facilitated greater prednisone-equivalent glucocorticoid exposure is important, he and his colleagues wrote, because these medications may put patients at higher risk of infection, cardiovascular disease, and diabetes – even in low doses and with short-term use. Notably, the median delay to the initiation of treatment was 29 days, regardless of prior authorization requirements. Dr. Wallace said the delays “likely reflect a combination of factors” – including infusion center waiting lists and patient-level factors – and that his team is “thinking about how to facilitate better access [to their practice’s infusion center] for those who are approved for treatment.”
The most common conditions for which infused medication was ordered were inflammatory arthritis (32%), vasculitis (23%), and IgG4-related disease (17%). The 225 patients in the study had an average age of 53 years.
Dr. Wallace reported that he has no relevant financial disclosures.
SOURCE: Wallace ZS et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24062.
Rheumatologist Zachary S. Wallace, MD, knew just how prior authorization requirements were impacting his staff time and work flow when he embarked on a study several years ago. Managing authorizations for infusible medications alone was about to become a full-time job for one of the administrative assistants in the rheumatology unit at Massachusetts General Hospital in Boston.
His research questions concerned patients. “There’s a lot of talk about how much onus prior authorization requirements put on providers and the practice,” Dr. Wallace said. ”I was interested in understanding what impact [these requirements] have on patients themselves.”
Dr. Wallace led a review of the EHRs of 225 patients for whom an infusible medication such as rituximab and infliximab was ordered by 1 of the 16 physicians in the rheumatology unit between July 2016 and June 2018. The findings – that patients who needed prior authorizations for infusible medications had a significantly longer time to treatment initiation and higher prednisone-equivalent glucocorticoid exposure – were reported online in Arthritis Care & Research.
Among patients whose authorizations were initially denied, these differences were “pretty drastic,” Dr. Wallace said. The median time to receiving a first infusion was 50 days, compared with 27 days when permission was not required, and glucocorticoid exposure during the 3 months following the request was 605 mg versus 160 mg.
Among patients whose authorizations were not denied, the median time to first infusion was 31 days, compared with 27 days when authorization was not required, and the mean glucocorticoid exposure over 3 months was 364 mg versus 160 mg.
“I hope that our findings will help facilitate discussions with insurance providers, pharmacy benefit managers, and state and federal legislators about the need to address the impact that prior authorization requirements have on patients and providers,” said Dr. Wallace, also of the clinical epidemiology program in the division of rheumatology, allergy and immunology at Massachusetts General, and an assistant professor of medicine at Harvard Medical School, Boston.
Of the 225 patients for whom an infusible medication was ordered, 71% required preauthorization. Of these, 79% were approved and 21% were denied after the first request. And in a finding that Dr. Wallace called “somewhat surprising,” 82% of the authorizations originally denied were approved after appeal.
All told, prior authorizations for infusible medications were eventually approved in all but a small number of cases. “We go through all this effort to get these prior authorizations approved, and 96% of the time, they were ultimately approved,” he said in an interview.
Christopher Phillips, MD, a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the American College of Rheumatology’s committee on rheumatologic care, said the findings “give further credence” to rheumatologists’ concerns. “We know [from our own experiences] that prior authorizations delay care, and we know that delays can cause harm to patients. We now have hard data backing up this assertion.”
Regarding the high number of authorization approvals, “there’s an argument to be made that for certain treatments and certain conditions where the success rate of appeals is high enough, you shouldn’t be subjecting these treatments to these [preauthorization] policies,” he said.
Calls for prior authorization reform
Most patients in the study (71%) had private insurance. But the findings also have implications for Medicare, Dr. Wallace said, as recent federal policies have expanded Medicare Advantage plans’ authority to use prior authorization in conjunction with step therapy for medications administered under Part B. Step therapy favors primary use of what insurers deem the most cost-effective therapies.
The ACR is one of almost 370 physician, patient, and health care organizations that are urging Congress to pass a bipartisan bill aimed at streamlining and standardizing prior authorization under the Medicare Advantage program. The legislation – Improving Seniors’ Timely Access to Care Act of 2019 (H.R. 3107) – was introduced by Reps. Suzan DelBene (D-Wash.), Mike Kelly (R-Pa.), Roger Marshall, MD (R-Kan.), and Ami Bera, MD (D-Calif.).
The bill calls for the creation of an electronic prior authorization program and a “real-time process for items and services that are routinely approved,” as well as greater Centers for Medicare & Medicaid Services oversight on how Medicare Advantage plans use prior authorization. Plans would be required to report to the CMS on the extent of their use of prior authorization and the rate of approvals or denials. They would also be held accountable for making timely prior authorization determinations and providing rationales for denials, according to a letter to Congress cosigned by the ACR.
In a press release about the legislation, Paula Marchetta, MD, president of the ACR, said that “the unregulated use of prior authorization has devolved into a time-consuming and obstructive process that often stalls or outright revokes patient access to medically necessary therapies.” She added that “many health care plans now use prior authorization indiscriminately.”
Cathryn Donaldson, director of communications for America’s Health Insurance Plans (AHIP), said in an email that prior authorization is used for less than 15% of covered services, and that, along with step therapy, it “helps ensure that patients receive care that is safe, effective, and necessary.” AHIP “knows that prior authorization can be improved,” she said, and is committed to streamlining the process.
A demonstration project on the automation of various parts of prior authorization is being coordinated with health information technology companies, plans, and providers, she noted.
The federal legislation is based at least partly on a consensus statement drafted by AHIP, the American Medical Association, and four other organizations representing hospitals, medical groups, and health plans on ways to improve the prior authorization process. Among the items mentioned in the statement is that “regular review” of services subject to prior authorization could help identify therapies that “no longer warrant” prior authorization because of low denial rates.
Outside of Medicare Advantage, the AMA is aware of at least 85 bills being introduced in states this year that address utilization management in commercial plans. Nearly all these bills attempt to reform prior authorization programs in some way, according to R. J. Mills, media relations coordinator for the AMA.
Rheumatologic patients hard hit
Off-label medication use was the most common reason (82%) for a prior authorization denial in the Massachusetts General study, even though 78% of the patients for whom infusible medications were prescribed had a condition with no Food and Drug Administration–approved treatment. Having such a condition was associated with 120% or 190% higher odds of having a denial in unadjusted and adjusted (for age and sex) analyses, Dr. Wallace and colleagues reported.
Moreover, nearly half (48%) of the patients with denials had already tried or were currently taking an oral disease-modifying antirheumatic drug, such as methotrexate.
The majority of denials were for the use of rituximab (70%), followed by infliximab (12%) and tocilizumab (12%). Most of the denials (79%) were appealed successfully through a peer-to-peer discussion. In five cases, the insurer’s preferred drug (for example, adalimumab) had to be used rather than the requested infusion (for example, infliximab).
Infused medications, many of which are biologics, are among the most expensive drugs prescribed for patients with rheumatic diseases. They were easiest for Dr. Wallace to study because of the way prior authorizations are handled in his unit, but prior authorization requirements are “widespread” in rheumatology practices across treatment types, he and Dr. Phillips said.
“Some of our relatively inexpensive treatments are subject to prior authorization requirements,” Dr. Phillips said. “We hear stories about prednisone needing a prior authorization sometimes.”
With respect to infusible medications, the insurance subcommittee is hearing from ACR members about seemingly increasing numbers of both clinical coverage reviews – for example, reviews of prior treatments – and site-of-care restrictions, Dr. Phillips noted. “Some carriers are insisting on infusions in non-hospital-based settings, for cost savings, or on home infusions, which are concerning because of [possible] infusion reactions and medical service availability.”
The application of step therapy to rheumatologic patients is troubling because of the “often unique medical circumstances of the patient,” Dr. Phillips said. “There are enough differences among the [tumor necrosis factor] antagonists, for instance, that make one more appropriate for a certain patient than another. Those differences are not brought into consideration with these policies.”
There are other ways in which prior authorization processes “are not well informed medically,” he said, recalling a case brought to the attention of the subcommittee in which a patient prescribed a biologic drug for psoriatic arthritis was denied authorization because “the documentation did not include a [disease activity measure] that is specific to RA and not used for psoriatic arthritis.”
It is not uncommon for authorizations for infusible medications to take 2 weeks or longer to secure – even when initially approved. In the AMA’s 2018 Prior Authorization Physician Survey, 65% reported waiting at least 1 business day for a decision and 26% reported waiting at least 3 business days for responses. “With infusibles, we’re absolutely dealing with a much longer time,” Dr. Phillips said.
In Dr. Wallace’s study, the finding that prior authorizations facilitated greater prednisone-equivalent glucocorticoid exposure is important, he and his colleagues wrote, because these medications may put patients at higher risk of infection, cardiovascular disease, and diabetes – even in low doses and with short-term use. Notably, the median delay to the initiation of treatment was 29 days, regardless of prior authorization requirements. Dr. Wallace said the delays “likely reflect a combination of factors” – including infusion center waiting lists and patient-level factors – and that his team is “thinking about how to facilitate better access [to their practice’s infusion center] for those who are approved for treatment.”
The most common conditions for which infused medication was ordered were inflammatory arthritis (32%), vasculitis (23%), and IgG4-related disease (17%). The 225 patients in the study had an average age of 53 years.
Dr. Wallace reported that he has no relevant financial disclosures.
SOURCE: Wallace ZS et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24062.
FROM ARTHRITIS CARE & RESEARCH
Study aims to define symptoms of Sjögren’s syndrome secondary to SLE
Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.
Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.
“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”
The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.
The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).
“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”
They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.
The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.
SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.
Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.
Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.
“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”
The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.
The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).
“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”
They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.
The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.
SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.
Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.
Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.
“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”
The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.
The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).
“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”
They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.
The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.
SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.
FROM THE JOURNAL OF RHEUMATOLOGY
ACR looks for continued growth in awareness of rheumatic diseases with latest annual campaign
With the help of a key celebrity spokesperson, the American College of Rheumatology is hoping Rheumatic Disease Awareness Month (RDAM) will continue to raise the profile of the related illnesses and help more patients recognize their symptoms and get on the road to treatment.
This year, the celebrity tapped to lead the now-annual campaign that began in September 2016 is tennis champion Venus Williams, who has been competing while battling Sjögren’s syndrome. She was diagnosed in 2011.
Having a high-profile individual like Venus Williams will “bring more awareness to not a specific illness but just rheumatic diseases in general,” Suleman Bhana, MD, chair of the ACR’s marketing and communications committee, said in an interview, adding that it is a way to help get attention from patients and their family members to be more aware of what they are facing when afflicted with a rheumatic disease.
It also helps to drive traffic to a website (simpletasks.org) set up to help build a community around rheumatic diseases, he noted.
“By signing up on the website, patients and others can get connected with wellness articles and can be informed about any advocacy opportunities in their local area or the national level,” said Dr. Bhana, a rheumatologist with Crystal Run Healthcare in Middletown, N.Y. “It helps us a lot from an ACR point of view just by getting the word out about rheumatic diseases.”
Dr. Bhana said that part of the success of the RDAM campaign is being measured by the number of people who sign up for the website. “Last year we had about 1,600 people sign up, which was more than double from the previous year and we are hoping to do even better this year now that we have Venus Williams as our spokesperson.”
But the campaign involves more than just a celebrity spokesperson and an online community to build awareness for rheumatic diseases and their associated symptoms and treatments. The ACR is working with patients to make sure their voices are heard on Capitol Hill to help ensure proper access to medical care and those treatments.
This year, the ACR – along with more than 100 advocates – met with members of Congress to push for policies that will benefit people with rheumatic diseases. One key item on the agenda targets the use of step therapy.
“This year the ACR’s Government Affairs Committee had a list of several pieces of legislation that they are looking at heavily. [One bill is about] having brakes on what is called step therapy, which is a fairly egregious practice by many insurers that forces patients to use different medications than what the physician and patient decide in their mutual doctor-patient relationship before they can use the medicine that was originally decided upon,” he said. “The reasons for this practice mostly are financial in that insurers get kickbacks from certain pharmaceutical companies, and that is what they term as preferred drugs. It’s a lot more than just cost savings. It’s about the insurers financially benefiting from patients rather than doing the right thing and preserving the doctor-patient relationship.”
One bill in particular that has been highlighted by the ACR is the Safe Step Act of 2019 (H.R. 2279), introduced by Rep. Raul Ruiz, MD (D-Calif.), and Rep. Brad Wenstrup, DPM (R-Ohio), would put limits on step therapy and create a clear process for patients and physicians to seek exemptions.
Other legislative actions that patients and the ACR were advocating for during the visits for RDAM included the EMPOWER for Health Act (H.R. 2781), which would help increase the number of pediatric subspecialists, including pediatric rheumatologists, through loan repayment for health professionals who agree to work at least 2 years in pediatric medicine, and the REDI Act (H.R. 1554), which would defer the accumulation on student loan interest while future doctors serve in a medical internship or residency program.
“The reality of pediatrics is that they don’t get well compensated as a pediatric rheumatologist subspecialist, so there is an ultimate financial disincentive for training pediatricians to go into rheumatology,” Dr. Bhana said. “So we are trying to get support for loan repayment for pediatric rheumatologists or rheumatology fellowship programs, which may help to incentivize young pediatricians to go into rheumatology to at least expand access to care.”
The RDAM campaign also provides useful contacts for an annual survey that the ACR conducts. This year’s survey found that access issues for both physicians and treatments persist, informing the agenda for the advocacy on Capitol Hill.
For example, the 2019 survey found that more than 60% of respondents had to wait at least 31 days from a physician referral to an initial rheumatologist appointment. Dr. Bhana noted that, in his practice, the wait can be 3 months or longer. A little more than 36% of respondents were able to get that initial appointment after referral in 30 days or less.
Additionally, nearly 47% of respondents were subjected to step therapy in the past year.
Treatment pricing was also raised as a concern in the survey, with a little more than 57% of respondents reporting difficulty affording treatments in the past year, and 25% reporting annual out-of-pocket spending at greater than $1,000, with more than 6% reporting annual out-of-pocket spending of greater than $5,000.
Despite all the challenges that lay ahead, Dr. Bhana believes that, as the campaign continues in its fourth year, it is having a positive impact.
“I think there is more awareness among patients to look up their symptoms and prompt their providers to look into, if not test for, rheumatic diseases, direct referrals, and I think because of these campaigns, we’ve gotten some indication that from a social media awareness that more patients are talking about it, about trying to get into seeing a physician.”
With the help of a key celebrity spokesperson, the American College of Rheumatology is hoping Rheumatic Disease Awareness Month (RDAM) will continue to raise the profile of the related illnesses and help more patients recognize their symptoms and get on the road to treatment.
This year, the celebrity tapped to lead the now-annual campaign that began in September 2016 is tennis champion Venus Williams, who has been competing while battling Sjögren’s syndrome. She was diagnosed in 2011.
Having a high-profile individual like Venus Williams will “bring more awareness to not a specific illness but just rheumatic diseases in general,” Suleman Bhana, MD, chair of the ACR’s marketing and communications committee, said in an interview, adding that it is a way to help get attention from patients and their family members to be more aware of what they are facing when afflicted with a rheumatic disease.
It also helps to drive traffic to a website (simpletasks.org) set up to help build a community around rheumatic diseases, he noted.
“By signing up on the website, patients and others can get connected with wellness articles and can be informed about any advocacy opportunities in their local area or the national level,” said Dr. Bhana, a rheumatologist with Crystal Run Healthcare in Middletown, N.Y. “It helps us a lot from an ACR point of view just by getting the word out about rheumatic diseases.”
Dr. Bhana said that part of the success of the RDAM campaign is being measured by the number of people who sign up for the website. “Last year we had about 1,600 people sign up, which was more than double from the previous year and we are hoping to do even better this year now that we have Venus Williams as our spokesperson.”
But the campaign involves more than just a celebrity spokesperson and an online community to build awareness for rheumatic diseases and their associated symptoms and treatments. The ACR is working with patients to make sure their voices are heard on Capitol Hill to help ensure proper access to medical care and those treatments.
This year, the ACR – along with more than 100 advocates – met with members of Congress to push for policies that will benefit people with rheumatic diseases. One key item on the agenda targets the use of step therapy.
“This year the ACR’s Government Affairs Committee had a list of several pieces of legislation that they are looking at heavily. [One bill is about] having brakes on what is called step therapy, which is a fairly egregious practice by many insurers that forces patients to use different medications than what the physician and patient decide in their mutual doctor-patient relationship before they can use the medicine that was originally decided upon,” he said. “The reasons for this practice mostly are financial in that insurers get kickbacks from certain pharmaceutical companies, and that is what they term as preferred drugs. It’s a lot more than just cost savings. It’s about the insurers financially benefiting from patients rather than doing the right thing and preserving the doctor-patient relationship.”
One bill in particular that has been highlighted by the ACR is the Safe Step Act of 2019 (H.R. 2279), introduced by Rep. Raul Ruiz, MD (D-Calif.), and Rep. Brad Wenstrup, DPM (R-Ohio), would put limits on step therapy and create a clear process for patients and physicians to seek exemptions.
Other legislative actions that patients and the ACR were advocating for during the visits for RDAM included the EMPOWER for Health Act (H.R. 2781), which would help increase the number of pediatric subspecialists, including pediatric rheumatologists, through loan repayment for health professionals who agree to work at least 2 years in pediatric medicine, and the REDI Act (H.R. 1554), which would defer the accumulation on student loan interest while future doctors serve in a medical internship or residency program.
“The reality of pediatrics is that they don’t get well compensated as a pediatric rheumatologist subspecialist, so there is an ultimate financial disincentive for training pediatricians to go into rheumatology,” Dr. Bhana said. “So we are trying to get support for loan repayment for pediatric rheumatologists or rheumatology fellowship programs, which may help to incentivize young pediatricians to go into rheumatology to at least expand access to care.”
The RDAM campaign also provides useful contacts for an annual survey that the ACR conducts. This year’s survey found that access issues for both physicians and treatments persist, informing the agenda for the advocacy on Capitol Hill.
For example, the 2019 survey found that more than 60% of respondents had to wait at least 31 days from a physician referral to an initial rheumatologist appointment. Dr. Bhana noted that, in his practice, the wait can be 3 months or longer. A little more than 36% of respondents were able to get that initial appointment after referral in 30 days or less.
Additionally, nearly 47% of respondents were subjected to step therapy in the past year.
Treatment pricing was also raised as a concern in the survey, with a little more than 57% of respondents reporting difficulty affording treatments in the past year, and 25% reporting annual out-of-pocket spending at greater than $1,000, with more than 6% reporting annual out-of-pocket spending of greater than $5,000.
Despite all the challenges that lay ahead, Dr. Bhana believes that, as the campaign continues in its fourth year, it is having a positive impact.
“I think there is more awareness among patients to look up their symptoms and prompt their providers to look into, if not test for, rheumatic diseases, direct referrals, and I think because of these campaigns, we’ve gotten some indication that from a social media awareness that more patients are talking about it, about trying to get into seeing a physician.”
With the help of a key celebrity spokesperson, the American College of Rheumatology is hoping Rheumatic Disease Awareness Month (RDAM) will continue to raise the profile of the related illnesses and help more patients recognize their symptoms and get on the road to treatment.
This year, the celebrity tapped to lead the now-annual campaign that began in September 2016 is tennis champion Venus Williams, who has been competing while battling Sjögren’s syndrome. She was diagnosed in 2011.
Having a high-profile individual like Venus Williams will “bring more awareness to not a specific illness but just rheumatic diseases in general,” Suleman Bhana, MD, chair of the ACR’s marketing and communications committee, said in an interview, adding that it is a way to help get attention from patients and their family members to be more aware of what they are facing when afflicted with a rheumatic disease.
It also helps to drive traffic to a website (simpletasks.org) set up to help build a community around rheumatic diseases, he noted.
“By signing up on the website, patients and others can get connected with wellness articles and can be informed about any advocacy opportunities in their local area or the national level,” said Dr. Bhana, a rheumatologist with Crystal Run Healthcare in Middletown, N.Y. “It helps us a lot from an ACR point of view just by getting the word out about rheumatic diseases.”
Dr. Bhana said that part of the success of the RDAM campaign is being measured by the number of people who sign up for the website. “Last year we had about 1,600 people sign up, which was more than double from the previous year and we are hoping to do even better this year now that we have Venus Williams as our spokesperson.”
But the campaign involves more than just a celebrity spokesperson and an online community to build awareness for rheumatic diseases and their associated symptoms and treatments. The ACR is working with patients to make sure their voices are heard on Capitol Hill to help ensure proper access to medical care and those treatments.
This year, the ACR – along with more than 100 advocates – met with members of Congress to push for policies that will benefit people with rheumatic diseases. One key item on the agenda targets the use of step therapy.
“This year the ACR’s Government Affairs Committee had a list of several pieces of legislation that they are looking at heavily. [One bill is about] having brakes on what is called step therapy, which is a fairly egregious practice by many insurers that forces patients to use different medications than what the physician and patient decide in their mutual doctor-patient relationship before they can use the medicine that was originally decided upon,” he said. “The reasons for this practice mostly are financial in that insurers get kickbacks from certain pharmaceutical companies, and that is what they term as preferred drugs. It’s a lot more than just cost savings. It’s about the insurers financially benefiting from patients rather than doing the right thing and preserving the doctor-patient relationship.”
One bill in particular that has been highlighted by the ACR is the Safe Step Act of 2019 (H.R. 2279), introduced by Rep. Raul Ruiz, MD (D-Calif.), and Rep. Brad Wenstrup, DPM (R-Ohio), would put limits on step therapy and create a clear process for patients and physicians to seek exemptions.
Other legislative actions that patients and the ACR were advocating for during the visits for RDAM included the EMPOWER for Health Act (H.R. 2781), which would help increase the number of pediatric subspecialists, including pediatric rheumatologists, through loan repayment for health professionals who agree to work at least 2 years in pediatric medicine, and the REDI Act (H.R. 1554), which would defer the accumulation on student loan interest while future doctors serve in a medical internship or residency program.
“The reality of pediatrics is that they don’t get well compensated as a pediatric rheumatologist subspecialist, so there is an ultimate financial disincentive for training pediatricians to go into rheumatology,” Dr. Bhana said. “So we are trying to get support for loan repayment for pediatric rheumatologists or rheumatology fellowship programs, which may help to incentivize young pediatricians to go into rheumatology to at least expand access to care.”
The RDAM campaign also provides useful contacts for an annual survey that the ACR conducts. This year’s survey found that access issues for both physicians and treatments persist, informing the agenda for the advocacy on Capitol Hill.
For example, the 2019 survey found that more than 60% of respondents had to wait at least 31 days from a physician referral to an initial rheumatologist appointment. Dr. Bhana noted that, in his practice, the wait can be 3 months or longer. A little more than 36% of respondents were able to get that initial appointment after referral in 30 days or less.
Additionally, nearly 47% of respondents were subjected to step therapy in the past year.
Treatment pricing was also raised as a concern in the survey, with a little more than 57% of respondents reporting difficulty affording treatments in the past year, and 25% reporting annual out-of-pocket spending at greater than $1,000, with more than 6% reporting annual out-of-pocket spending of greater than $5,000.
Despite all the challenges that lay ahead, Dr. Bhana believes that, as the campaign continues in its fourth year, it is having a positive impact.
“I think there is more awareness among patients to look up their symptoms and prompt their providers to look into, if not test for, rheumatic diseases, direct referrals, and I think because of these campaigns, we’ve gotten some indication that from a social media awareness that more patients are talking about it, about trying to get into seeing a physician.”
Antimalarial exposure above recommended doses in lupus contributes most retinopathy risk
Antimalarial retinal complications occurred in about 5% of patients with systemic lupus erythematosus (SLE) exposed to hydroxychloroquine or chloroquine during an average of nearly 13 years of follow-up, without any cases of retinal toxicity occurring within the first 5 years of use, according to findings from a case-control study.
The rate of retinal complications observed in the study is slightly lower or within the range reported in other studies of antimalarial use by patients with SLE, first author Elvis-Raymond Mukwikwi of the University of Montreal and coauthors from McGill University, Montreal, reported in the Journal of Rheumatology.
Hydroxychloroquine (HCQ) and chloroquine (CQ) are commonly used to treat SLE and rheumatoid arthritis, and they are being investigated for use in diabetes, cancer, and cardiovascular disease. However, in rare cases, the drugs can lead to irreversible retinopathy.
To better understand the factors associated with retinopathy, the researchers analyzed data from 326 records obtained from the McGill University Health Center Lupus Clinic Registry. A total of 18 patients (5.5%) had confirmed retinal toxicity, and the investigators matched each of these patients to 3 control patients with SLE and exposure to HCQ/CQ who did not develop retinopathy and had the same duration of SLE and age at SLE diagnosis.
The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years, and the maximum number was 33 years. Overall, 17 retinopathy cases had exposure to HCQ, and 12 of those cases (71%) received average doses higher than current recommendations. Eight patients were exposed to average daily doses of HCQ higher than 5 mg/kg and four to average daily doses of CQ above 2.3 mg/kg. Exposure to an average dose higher than currently recommended occurred in 49% of controls. The exposure to doses higher than current recommendations was “not surprising given that these were issued in 2016 and most of our patients had been taking HCQ for longer than this,” the authors wrote.
High-dose exposure was common, with 83% of controls and all retinopathy cases having been exposed to HCQ/CQ doses above recommendations, as determined during at least one annual assessment.
Among patients with retinopathy, exposure to CQ was three times more frequent than it was for those without the condition (39% vs. 13%; 95% confidence interval, 1.8%-52%), although all of the patients exposed to CQ also were exposed to long periods of HCQ, making it impossible to determine retinopathy risk to CQ exposure alone.
The researchers also found gaps in monitoring. In the 5 years before discontinuation of medication, 53% of cases had missed one or more annual ophthalmologic assessments to screen for retinal damage, compared with 75% of controls.
Concomitant renal damage, believed to be a risk factor for retinal toxicity, occurred more often in the retinopathy group, though the difference failed to meet statistical significance (23% versus 15%). Patients with retinopathy were less likely to be Caucasian (61% versus 74%), but this also did not reach statistical significance.
The authors did not disclose information on funding or conflicts of interest.
SOURCE: Mukwikwi ER et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181102
Antimalarial retinal complications occurred in about 5% of patients with systemic lupus erythematosus (SLE) exposed to hydroxychloroquine or chloroquine during an average of nearly 13 years of follow-up, without any cases of retinal toxicity occurring within the first 5 years of use, according to findings from a case-control study.
The rate of retinal complications observed in the study is slightly lower or within the range reported in other studies of antimalarial use by patients with SLE, first author Elvis-Raymond Mukwikwi of the University of Montreal and coauthors from McGill University, Montreal, reported in the Journal of Rheumatology.
Hydroxychloroquine (HCQ) and chloroquine (CQ) are commonly used to treat SLE and rheumatoid arthritis, and they are being investigated for use in diabetes, cancer, and cardiovascular disease. However, in rare cases, the drugs can lead to irreversible retinopathy.
To better understand the factors associated with retinopathy, the researchers analyzed data from 326 records obtained from the McGill University Health Center Lupus Clinic Registry. A total of 18 patients (5.5%) had confirmed retinal toxicity, and the investigators matched each of these patients to 3 control patients with SLE and exposure to HCQ/CQ who did not develop retinopathy and had the same duration of SLE and age at SLE diagnosis.
The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years, and the maximum number was 33 years. Overall, 17 retinopathy cases had exposure to HCQ, and 12 of those cases (71%) received average doses higher than current recommendations. Eight patients were exposed to average daily doses of HCQ higher than 5 mg/kg and four to average daily doses of CQ above 2.3 mg/kg. Exposure to an average dose higher than currently recommended occurred in 49% of controls. The exposure to doses higher than current recommendations was “not surprising given that these were issued in 2016 and most of our patients had been taking HCQ for longer than this,” the authors wrote.
High-dose exposure was common, with 83% of controls and all retinopathy cases having been exposed to HCQ/CQ doses above recommendations, as determined during at least one annual assessment.
Among patients with retinopathy, exposure to CQ was three times more frequent than it was for those without the condition (39% vs. 13%; 95% confidence interval, 1.8%-52%), although all of the patients exposed to CQ also were exposed to long periods of HCQ, making it impossible to determine retinopathy risk to CQ exposure alone.
The researchers also found gaps in monitoring. In the 5 years before discontinuation of medication, 53% of cases had missed one or more annual ophthalmologic assessments to screen for retinal damage, compared with 75% of controls.
Concomitant renal damage, believed to be a risk factor for retinal toxicity, occurred more often in the retinopathy group, though the difference failed to meet statistical significance (23% versus 15%). Patients with retinopathy were less likely to be Caucasian (61% versus 74%), but this also did not reach statistical significance.
The authors did not disclose information on funding or conflicts of interest.
SOURCE: Mukwikwi ER et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181102
Antimalarial retinal complications occurred in about 5% of patients with systemic lupus erythematosus (SLE) exposed to hydroxychloroquine or chloroquine during an average of nearly 13 years of follow-up, without any cases of retinal toxicity occurring within the first 5 years of use, according to findings from a case-control study.
The rate of retinal complications observed in the study is slightly lower or within the range reported in other studies of antimalarial use by patients with SLE, first author Elvis-Raymond Mukwikwi of the University of Montreal and coauthors from McGill University, Montreal, reported in the Journal of Rheumatology.
Hydroxychloroquine (HCQ) and chloroquine (CQ) are commonly used to treat SLE and rheumatoid arthritis, and they are being investigated for use in diabetes, cancer, and cardiovascular disease. However, in rare cases, the drugs can lead to irreversible retinopathy.
To better understand the factors associated with retinopathy, the researchers analyzed data from 326 records obtained from the McGill University Health Center Lupus Clinic Registry. A total of 18 patients (5.5%) had confirmed retinal toxicity, and the investigators matched each of these patients to 3 control patients with SLE and exposure to HCQ/CQ who did not develop retinopathy and had the same duration of SLE and age at SLE diagnosis.
The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years, and the maximum number was 33 years. Overall, 17 retinopathy cases had exposure to HCQ, and 12 of those cases (71%) received average doses higher than current recommendations. Eight patients were exposed to average daily doses of HCQ higher than 5 mg/kg and four to average daily doses of CQ above 2.3 mg/kg. Exposure to an average dose higher than currently recommended occurred in 49% of controls. The exposure to doses higher than current recommendations was “not surprising given that these were issued in 2016 and most of our patients had been taking HCQ for longer than this,” the authors wrote.
High-dose exposure was common, with 83% of controls and all retinopathy cases having been exposed to HCQ/CQ doses above recommendations, as determined during at least one annual assessment.
Among patients with retinopathy, exposure to CQ was three times more frequent than it was for those without the condition (39% vs. 13%; 95% confidence interval, 1.8%-52%), although all of the patients exposed to CQ also were exposed to long periods of HCQ, making it impossible to determine retinopathy risk to CQ exposure alone.
The researchers also found gaps in monitoring. In the 5 years before discontinuation of medication, 53% of cases had missed one or more annual ophthalmologic assessments to screen for retinal damage, compared with 75% of controls.
Concomitant renal damage, believed to be a risk factor for retinal toxicity, occurred more often in the retinopathy group, though the difference failed to meet statistical significance (23% versus 15%). Patients with retinopathy were less likely to be Caucasian (61% versus 74%), but this also did not reach statistical significance.
The authors did not disclose information on funding or conflicts of interest.
SOURCE: Mukwikwi ER et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181102
FROM THE JOURNAL OF RHEUMATOLOGY
FDA approves nintedanib for scleroderma interstitial lung disease
The Food and Drug Administration has approved nintedanib (Ofev) for the rare but sometimes deadly form of interstitial lung disease that’s caused by systemic sclerosis, or scleroderma.
Although scleroderma itself is rare, half of those patients present with scleroderma-related interstitial lung disease (SSc-ILD), and it remains the leading cause of death in scleroderma patients because it can lead to loss of pulmonary function. Nintedanib appears to slow the progress of SSc-ILD and is the first treatment approved for it, according to a news release from the FDA.
The approval is based on a randomized, double-blind, placebo-controlled trial of 576 patients aged 20-79 years with SSc-ILD. The primary efficacy endpoint was forced vital capacity, and patients on nintedanib showed less decline than did those on placebo.
The most frequent serious adverse event reported in this trial was pneumonia (2.8% with nintedanib vs. 0.3% with placebo). Adverse reactions that led to permanent dose reductions occurred in 34% of nintedanib patients and 4% of placebo-treated patients; the most common of these was diarrhea.
The full prescribing information, which is available on the FDA website, includes warnings for patients with moderate to severe hepatic impairment, elevated liver enzymes, and drug-induced liver injury, as well as those with gastrointestinal disorders. Nintedanib may cause embryo-fetal toxicity, so women of childbearing age should be counseled to avoid pregnancy while taking this drug.
Nintedanib received both Priority Review and Orphan Drug designation. The former meant the FDA intends to take action on the application within 6 months because the agency has determined that, if approved, it would have important effects on treatment of a serious condition. The latter provides incentives to assist and encourage development of drugs for rare diseases. The drug was approved in 2014 for adult patients with idiopathic pulmonary fibrosis, another interstitial lung disease.
The full release is available on the FDA website.
The Food and Drug Administration has approved nintedanib (Ofev) for the rare but sometimes deadly form of interstitial lung disease that’s caused by systemic sclerosis, or scleroderma.
Although scleroderma itself is rare, half of those patients present with scleroderma-related interstitial lung disease (SSc-ILD), and it remains the leading cause of death in scleroderma patients because it can lead to loss of pulmonary function. Nintedanib appears to slow the progress of SSc-ILD and is the first treatment approved for it, according to a news release from the FDA.
The approval is based on a randomized, double-blind, placebo-controlled trial of 576 patients aged 20-79 years with SSc-ILD. The primary efficacy endpoint was forced vital capacity, and patients on nintedanib showed less decline than did those on placebo.
The most frequent serious adverse event reported in this trial was pneumonia (2.8% with nintedanib vs. 0.3% with placebo). Adverse reactions that led to permanent dose reductions occurred in 34% of nintedanib patients and 4% of placebo-treated patients; the most common of these was diarrhea.
The full prescribing information, which is available on the FDA website, includes warnings for patients with moderate to severe hepatic impairment, elevated liver enzymes, and drug-induced liver injury, as well as those with gastrointestinal disorders. Nintedanib may cause embryo-fetal toxicity, so women of childbearing age should be counseled to avoid pregnancy while taking this drug.
Nintedanib received both Priority Review and Orphan Drug designation. The former meant the FDA intends to take action on the application within 6 months because the agency has determined that, if approved, it would have important effects on treatment of a serious condition. The latter provides incentives to assist and encourage development of drugs for rare diseases. The drug was approved in 2014 for adult patients with idiopathic pulmonary fibrosis, another interstitial lung disease.
The full release is available on the FDA website.
The Food and Drug Administration has approved nintedanib (Ofev) for the rare but sometimes deadly form of interstitial lung disease that’s caused by systemic sclerosis, or scleroderma.
Although scleroderma itself is rare, half of those patients present with scleroderma-related interstitial lung disease (SSc-ILD), and it remains the leading cause of death in scleroderma patients because it can lead to loss of pulmonary function. Nintedanib appears to slow the progress of SSc-ILD and is the first treatment approved for it, according to a news release from the FDA.
The approval is based on a randomized, double-blind, placebo-controlled trial of 576 patients aged 20-79 years with SSc-ILD. The primary efficacy endpoint was forced vital capacity, and patients on nintedanib showed less decline than did those on placebo.
The most frequent serious adverse event reported in this trial was pneumonia (2.8% with nintedanib vs. 0.3% with placebo). Adverse reactions that led to permanent dose reductions occurred in 34% of nintedanib patients and 4% of placebo-treated patients; the most common of these was diarrhea.
The full prescribing information, which is available on the FDA website, includes warnings for patients with moderate to severe hepatic impairment, elevated liver enzymes, and drug-induced liver injury, as well as those with gastrointestinal disorders. Nintedanib may cause embryo-fetal toxicity, so women of childbearing age should be counseled to avoid pregnancy while taking this drug.
Nintedanib received both Priority Review and Orphan Drug designation. The former meant the FDA intends to take action on the application within 6 months because the agency has determined that, if approved, it would have important effects on treatment of a serious condition. The latter provides incentives to assist and encourage development of drugs for rare diseases. The drug was approved in 2014 for adult patients with idiopathic pulmonary fibrosis, another interstitial lung disease.
The full release is available on the FDA website.
Cannabidiol may interact with rheumatologic drugs
A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.
“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”
The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.
CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.
The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.
This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.
The investigators declared no conflicts of interest, and there was no specific funding for the study.
SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.
A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.
“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”
The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.
CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.
The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.
This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.
The investigators declared no conflicts of interest, and there was no specific funding for the study.
SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.
A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.
“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”
The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.
CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.
The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.
This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.
The investigators declared no conflicts of interest, and there was no specific funding for the study.
SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.
FROM RHEUMATOLOGY