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Efinaconazole topical solution effective against early onychomycosis
Patients with early onychomycosis can be effectively treated with once-daily efinaconazole topical solution, 10%, according to data from more than 1,000 patients.
“Early treatment before the disease progresses to total dystrophic onychomycosis can increase cure rate and may avoid the need for systemic treatments,” wrote study author Dr. Phoebe Rich, a dermatologist in group practice in Portland, Ore.
The study used two identical multicenter, randomized, double-blind, vehicle-controlled trials. Of 1,655 subjects, 1,526 underwent randomization, and subjects were categorized based on disease duration at baseline. A total of 74 subjects had onychomycosis for less than 1 year, 682 for 1-5 years, and 770 for more than 5 years. The primary endpoint was complete cure rate – defined as 0% clinical involvement of target toenail, and both negative results on a potassium hydroxide examination and a fungal culture – after 52 weeks (J. Drugs Dermatol. 2015;14:58-62).
After 52 weeks, 42.6% of patients with a baseline disease duration of less than 1 year had a complete cure with efinaconazole, compared with 16.7% on a vehicle (control). In the 1- to 5-year group, 17.1% of patients with a baseline disease duration had a complete cure with efinaconazole, compared with 4.4% on vehicle (P < .001); in the group of subjects with a disease duration longer than 5 years, 16.2% of patients had a complete cure on efinaconazole, compared with 2.5% on vehicle (P < .001).
Additionally, 28.3% of patients with no other toenails affected at baseline had a complete cure with efinaconazole, compared with 23.7% on vehicle; 18.6% of patients with one to two nontarget toenails affected at baseline had a complete cure with efinaconazole, compared with 4.9% on vehicle (P < .001); and 16.5% of patients with more than two nontarget toenails affected at baseline had a complete cure on efinaconazole, compared with 0.1% on vehicle (P < .001).
“The availability of an effective topical treatment for onychomycosis could encourage earlier treatment and prevent the progression of the disease, where it would become more difficult to treat successfully,” said Dr. Rich, who also cautioned that the study’s 52-week length “may be too brief to evaluate a clinical cure in onychomycosis.”
Dr. Rich has served as a paid consultant to Valeant Pharmaceuticals and was a principal investigator in the pivotal trials with efinaconazole topical solution, 10%.
Patients with early onychomycosis can be effectively treated with once-daily efinaconazole topical solution, 10%, according to data from more than 1,000 patients.
“Early treatment before the disease progresses to total dystrophic onychomycosis can increase cure rate and may avoid the need for systemic treatments,” wrote study author Dr. Phoebe Rich, a dermatologist in group practice in Portland, Ore.
The study used two identical multicenter, randomized, double-blind, vehicle-controlled trials. Of 1,655 subjects, 1,526 underwent randomization, and subjects were categorized based on disease duration at baseline. A total of 74 subjects had onychomycosis for less than 1 year, 682 for 1-5 years, and 770 for more than 5 years. The primary endpoint was complete cure rate – defined as 0% clinical involvement of target toenail, and both negative results on a potassium hydroxide examination and a fungal culture – after 52 weeks (J. Drugs Dermatol. 2015;14:58-62).
After 52 weeks, 42.6% of patients with a baseline disease duration of less than 1 year had a complete cure with efinaconazole, compared with 16.7% on a vehicle (control). In the 1- to 5-year group, 17.1% of patients with a baseline disease duration had a complete cure with efinaconazole, compared with 4.4% on vehicle (P < .001); in the group of subjects with a disease duration longer than 5 years, 16.2% of patients had a complete cure on efinaconazole, compared with 2.5% on vehicle (P < .001).
Additionally, 28.3% of patients with no other toenails affected at baseline had a complete cure with efinaconazole, compared with 23.7% on vehicle; 18.6% of patients with one to two nontarget toenails affected at baseline had a complete cure with efinaconazole, compared with 4.9% on vehicle (P < .001); and 16.5% of patients with more than two nontarget toenails affected at baseline had a complete cure on efinaconazole, compared with 0.1% on vehicle (P < .001).
“The availability of an effective topical treatment for onychomycosis could encourage earlier treatment and prevent the progression of the disease, where it would become more difficult to treat successfully,” said Dr. Rich, who also cautioned that the study’s 52-week length “may be too brief to evaluate a clinical cure in onychomycosis.”
Dr. Rich has served as a paid consultant to Valeant Pharmaceuticals and was a principal investigator in the pivotal trials with efinaconazole topical solution, 10%.
Patients with early onychomycosis can be effectively treated with once-daily efinaconazole topical solution, 10%, according to data from more than 1,000 patients.
“Early treatment before the disease progresses to total dystrophic onychomycosis can increase cure rate and may avoid the need for systemic treatments,” wrote study author Dr. Phoebe Rich, a dermatologist in group practice in Portland, Ore.
The study used two identical multicenter, randomized, double-blind, vehicle-controlled trials. Of 1,655 subjects, 1,526 underwent randomization, and subjects were categorized based on disease duration at baseline. A total of 74 subjects had onychomycosis for less than 1 year, 682 for 1-5 years, and 770 for more than 5 years. The primary endpoint was complete cure rate – defined as 0% clinical involvement of target toenail, and both negative results on a potassium hydroxide examination and a fungal culture – after 52 weeks (J. Drugs Dermatol. 2015;14:58-62).
After 52 weeks, 42.6% of patients with a baseline disease duration of less than 1 year had a complete cure with efinaconazole, compared with 16.7% on a vehicle (control). In the 1- to 5-year group, 17.1% of patients with a baseline disease duration had a complete cure with efinaconazole, compared with 4.4% on vehicle (P < .001); in the group of subjects with a disease duration longer than 5 years, 16.2% of patients had a complete cure on efinaconazole, compared with 2.5% on vehicle (P < .001).
Additionally, 28.3% of patients with no other toenails affected at baseline had a complete cure with efinaconazole, compared with 23.7% on vehicle; 18.6% of patients with one to two nontarget toenails affected at baseline had a complete cure with efinaconazole, compared with 4.9% on vehicle (P < .001); and 16.5% of patients with more than two nontarget toenails affected at baseline had a complete cure on efinaconazole, compared with 0.1% on vehicle (P < .001).
“The availability of an effective topical treatment for onychomycosis could encourage earlier treatment and prevent the progression of the disease, where it would become more difficult to treat successfully,” said Dr. Rich, who also cautioned that the study’s 52-week length “may be too brief to evaluate a clinical cure in onychomycosis.”
Dr. Rich has served as a paid consultant to Valeant Pharmaceuticals and was a principal investigator in the pivotal trials with efinaconazole topical solution, 10%.
FROM THE JOURNAL OF DRUGS IN DERMATOLOGY
Key clinical point: Once-daily efinaconazole topical solution, 10%, can be effective in treating patients with early onychomycosis.
Major finding: After 52 weeks of treatment, 42.6% of patients with a baseline disease duration of less than 1 year had a complete cure with efinaconazole, compared with 16.7% on a control solution.
Data source: Two multicenter, randomized, double-blind vehicle-controlled studies including 1,655 adults aged 18-70 years.
Disclosures: Dr. Phoebe Rich has served as a paid consultant to Valeant Pharmaceuticals and was a principal investigator in the pivotal trials with efinaconazole topical solution, 10%.
Reducing abatacept feasible for poor-prognosis early RA patients
Patients with poor-prognosis early rheumatoid arthritis who have been on a regimen of abatacept for at least 1 year and have low disease activity scores can safely scale back their medication doses, according to the findings of a substudy of a phase III trial.
“Drug-free remission remains a therapeutic goal in RA [rheumatoid arthritis], [but] in established RA, withdrawal of biological therapy generally leads to loss of remission for the majority of patients,” wrote the study’s authors, led by Dr. René Westhovens of the Katholieke Universiteit in Leuven, Belgium. “However, dose reduction is a feasible strategy for some patients ... [and] in early RA, dose reduction is possible for the large majority of patients.”
Dr. Westhovens and his coinvestigators crafted a substudy from the existing AGREE (Abatacept study to gauge remission and joint damage progression in methotrexate-naive patients with early erosive rheumatoid arthritis) trial, using 35 of the 87 sites enrolling patients in the larger study. Substudy participants were required to have a 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 after 2 years (701 days) in the AGREE trial (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-206149]).
In total, 108 patients were randomized into two groups: Fifty-eight subjects stayed on the AGREE trial dose of about 10 mg/kg abatacept, and 50 subjects began a lower dose of about 5 mg/kg abatacept. Mean age of patients in these groups was 50-51 years, and 76%-82% were female. From the 10-mg/kg and 5-mg/kg groups, three and five patients, respectively, discontinued, while four per group returned to open-label abatacept. The primary outcome over 12 months was time to disease relapse, which was defined as additional disease-modifying antirheumatic drugs, at least two courses high-dose steroids, return to open-label abatacept at about 10 mg/kg, or a DAS28 (with C-reactive protein [CRP]) of at least 3.2 at two consecutive visits. At baseline, the mean DAS28-CRP score in each group was 2.1.
The proportion of subjects experiencing disease relapse did not differ significantly between the two groups: 18 out of 58 (31%) in the 10-mg/kg group, and 17 out of 50 (34%) in the 5-mg/kg group (hazard ratio, 0.87; 95% confidence interval, 0.45-1.69). That occurred despite an average steady-state trough serum concentration of 20.3-24.1 mcg/mL in the 10-mg/kg group and 8.8-12.0 mcg/mL in the 5-mg/kg group.
“Considering the potential to alter the course of disease in some patients with early RA, along with the safety and health economic benefits in avoiding unnecessary drug exposure, timely induction of biological agents (preferably in combination with methotrexate), followed by dose reduction, might be a therapeutic option in [appropriate] patients,” Dr. Westhovens and his associates wrote.
The AGREE study and related statistical analyses were funded and performed by Bristol-Myers Squibb. Several coauthors are affiliated with or employed by Bristol-Myers Squibb, and disclosed other potential conflicts of interest.
Patients with poor-prognosis early rheumatoid arthritis who have been on a regimen of abatacept for at least 1 year and have low disease activity scores can safely scale back their medication doses, according to the findings of a substudy of a phase III trial.
“Drug-free remission remains a therapeutic goal in RA [rheumatoid arthritis], [but] in established RA, withdrawal of biological therapy generally leads to loss of remission for the majority of patients,” wrote the study’s authors, led by Dr. René Westhovens of the Katholieke Universiteit in Leuven, Belgium. “However, dose reduction is a feasible strategy for some patients ... [and] in early RA, dose reduction is possible for the large majority of patients.”
Dr. Westhovens and his coinvestigators crafted a substudy from the existing AGREE (Abatacept study to gauge remission and joint damage progression in methotrexate-naive patients with early erosive rheumatoid arthritis) trial, using 35 of the 87 sites enrolling patients in the larger study. Substudy participants were required to have a 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 after 2 years (701 days) in the AGREE trial (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-206149]).
In total, 108 patients were randomized into two groups: Fifty-eight subjects stayed on the AGREE trial dose of about 10 mg/kg abatacept, and 50 subjects began a lower dose of about 5 mg/kg abatacept. Mean age of patients in these groups was 50-51 years, and 76%-82% were female. From the 10-mg/kg and 5-mg/kg groups, three and five patients, respectively, discontinued, while four per group returned to open-label abatacept. The primary outcome over 12 months was time to disease relapse, which was defined as additional disease-modifying antirheumatic drugs, at least two courses high-dose steroids, return to open-label abatacept at about 10 mg/kg, or a DAS28 (with C-reactive protein [CRP]) of at least 3.2 at two consecutive visits. At baseline, the mean DAS28-CRP score in each group was 2.1.
The proportion of subjects experiencing disease relapse did not differ significantly between the two groups: 18 out of 58 (31%) in the 10-mg/kg group, and 17 out of 50 (34%) in the 5-mg/kg group (hazard ratio, 0.87; 95% confidence interval, 0.45-1.69). That occurred despite an average steady-state trough serum concentration of 20.3-24.1 mcg/mL in the 10-mg/kg group and 8.8-12.0 mcg/mL in the 5-mg/kg group.
“Considering the potential to alter the course of disease in some patients with early RA, along with the safety and health economic benefits in avoiding unnecessary drug exposure, timely induction of biological agents (preferably in combination with methotrexate), followed by dose reduction, might be a therapeutic option in [appropriate] patients,” Dr. Westhovens and his associates wrote.
The AGREE study and related statistical analyses were funded and performed by Bristol-Myers Squibb. Several coauthors are affiliated with or employed by Bristol-Myers Squibb, and disclosed other potential conflicts of interest.
Patients with poor-prognosis early rheumatoid arthritis who have been on a regimen of abatacept for at least 1 year and have low disease activity scores can safely scale back their medication doses, according to the findings of a substudy of a phase III trial.
“Drug-free remission remains a therapeutic goal in RA [rheumatoid arthritis], [but] in established RA, withdrawal of biological therapy generally leads to loss of remission for the majority of patients,” wrote the study’s authors, led by Dr. René Westhovens of the Katholieke Universiteit in Leuven, Belgium. “However, dose reduction is a feasible strategy for some patients ... [and] in early RA, dose reduction is possible for the large majority of patients.”
Dr. Westhovens and his coinvestigators crafted a substudy from the existing AGREE (Abatacept study to gauge remission and joint damage progression in methotrexate-naive patients with early erosive rheumatoid arthritis) trial, using 35 of the 87 sites enrolling patients in the larger study. Substudy participants were required to have a 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 after 2 years (701 days) in the AGREE trial (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-206149]).
In total, 108 patients were randomized into two groups: Fifty-eight subjects stayed on the AGREE trial dose of about 10 mg/kg abatacept, and 50 subjects began a lower dose of about 5 mg/kg abatacept. Mean age of patients in these groups was 50-51 years, and 76%-82% were female. From the 10-mg/kg and 5-mg/kg groups, three and five patients, respectively, discontinued, while four per group returned to open-label abatacept. The primary outcome over 12 months was time to disease relapse, which was defined as additional disease-modifying antirheumatic drugs, at least two courses high-dose steroids, return to open-label abatacept at about 10 mg/kg, or a DAS28 (with C-reactive protein [CRP]) of at least 3.2 at two consecutive visits. At baseline, the mean DAS28-CRP score in each group was 2.1.
The proportion of subjects experiencing disease relapse did not differ significantly between the two groups: 18 out of 58 (31%) in the 10-mg/kg group, and 17 out of 50 (34%) in the 5-mg/kg group (hazard ratio, 0.87; 95% confidence interval, 0.45-1.69). That occurred despite an average steady-state trough serum concentration of 20.3-24.1 mcg/mL in the 10-mg/kg group and 8.8-12.0 mcg/mL in the 5-mg/kg group.
“Considering the potential to alter the course of disease in some patients with early RA, along with the safety and health economic benefits in avoiding unnecessary drug exposure, timely induction of biological agents (preferably in combination with methotrexate), followed by dose reduction, might be a therapeutic option in [appropriate] patients,” Dr. Westhovens and his associates wrote.
The AGREE study and related statistical analyses were funded and performed by Bristol-Myers Squibb. Several coauthors are affiliated with or employed by Bristol-Myers Squibb, and disclosed other potential conflicts of interest.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: Patients with poor-prognosis early rheumatoid arthritis and DAS28-ESR of less than 2.6 after at least 1 year on abatacept (10 mg/kg) should have the option of reducing their dose.
Major finding: The proportion of subjects experiencing disease relapse did not differ significantly between the 10-mg/kg and the 5-mg/kg groups (31% vs. 34%, respectively; HR, 0.87; 95% confidence interval, 0.45-1.69).
Data source: A 1-year, multinational, randomized, double-blind, two-arm, parallel-dosing, exploratory substudy of 108 patients in the AGREE trial.
Disclosures: Several coauthors disclosed ties with Bristol-Myers Squibb, which markets abatacept and funded the study and related analyses.
Antibody elimination may mark radiographic outcomes in RA
The elimination of anticitrullinated vimentin antibodies during early antirheumatic therapy in rheumatoid arthritis patients may significantly increase the likelihood of positive radiographic outcomes, according to findings from a longitudinal cohort study.
“The development of serological tests for [autoantibodies recognizing citrullinated proteins (ACPA)] detection have improved the ability to diagnose rheumatoid arthritis [RA] at an early stage and to identify patients at increased risk of a severe disease course,” wrote lead author Dr. Alf Kastbom of the Karolinska Institute in Stockholm, and his associates (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-205698]). “These clinically very useful tests do not, however, formally address the question of which specific citrullinated autoantigens are targeted.”
Dr. Kastbom and his coinvestigators longitudinally analyzed serum samples from 316 of 487 patients with early RA (symptoms < 1 year) who had participated in the Swedish Farmacotherapy (SWEFOT) trial, a randomized, nonblinded trial. These 316 patients had baseline and 3-month serum samples available that were analyzed for any antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides that were derived from vimentin (cVim), fibrinogen (cFib), and alpha-enolase (CEP-1).
For the first 3 months, all patients received methotrexate. Next, patients who were deemed “methotrexate monotherapy–inadequate responders” were subsequently randomized into cohorts that received add-on therapy with either sulfasalazine and hydroxychloroquine or infliximab. The investigators again assessed ACPA levels at 12 and 24 months after commencement of therapy in these subjects and used this 2-year follow-up period to compare proportions of antibody-positive patients and relative changes in antibody levels across ACPA specificities, as well as therapeutic responses and radiographic progressions.
Dr. Kastbom and his coauthors found that changes in antibody status within the first 3 months were most closely associated with radiographic progression of RA over the 2-year study period. Specifically, subjects who experienced significant decreases in anti-cVim antibodies in the first 3 months had lower rates of radiographic progression and lower total van der Heijde modified Sharp score (SHS) after 2 years than did those whose anti-cVim antibody levels remained positive (P = .012 and P = .015, respectively). Anti-cVim antibody results were also adjusted for baseline 28-joint disease activity score, baseline erosions, current smoking status, sex, and European League Against Rheumatism response at 3 months (P = .005 for SHS progression > 1 and P = .013 for SHS progression > 5, respectively).
However, no significant relationships with radiographic progression were found in the anti-cFib and anti-CEP-1 antibody seroreversions. Median antibody levels of all tested ACPAs declined during initial methotrexate therapy and after commencement of add-on therapy, but the investigators found no significant association between treatment regimen and radiographic progression.
“It is intriguing to see that our study clearly demonstrates an association between the early disappearance of specific anti-cVim antibodies and less radiological progression,” wrote Dr. Kastbom and his colleagues, adding that the findings of this study should “encourage further work to explore the prognostic potential of repeated measurements of different ACPA specificities in early RA.”
This study was financed by grants from European Union–funded FP7 projects and several Swedish institutions. Several coauthors also disclosed individual ties to various pharmaceutical companies.
The elimination of anticitrullinated vimentin antibodies during early antirheumatic therapy in rheumatoid arthritis patients may significantly increase the likelihood of positive radiographic outcomes, according to findings from a longitudinal cohort study.
“The development of serological tests for [autoantibodies recognizing citrullinated proteins (ACPA)] detection have improved the ability to diagnose rheumatoid arthritis [RA] at an early stage and to identify patients at increased risk of a severe disease course,” wrote lead author Dr. Alf Kastbom of the Karolinska Institute in Stockholm, and his associates (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-205698]). “These clinically very useful tests do not, however, formally address the question of which specific citrullinated autoantigens are targeted.”
Dr. Kastbom and his coinvestigators longitudinally analyzed serum samples from 316 of 487 patients with early RA (symptoms < 1 year) who had participated in the Swedish Farmacotherapy (SWEFOT) trial, a randomized, nonblinded trial. These 316 patients had baseline and 3-month serum samples available that were analyzed for any antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides that were derived from vimentin (cVim), fibrinogen (cFib), and alpha-enolase (CEP-1).
For the first 3 months, all patients received methotrexate. Next, patients who were deemed “methotrexate monotherapy–inadequate responders” were subsequently randomized into cohorts that received add-on therapy with either sulfasalazine and hydroxychloroquine or infliximab. The investigators again assessed ACPA levels at 12 and 24 months after commencement of therapy in these subjects and used this 2-year follow-up period to compare proportions of antibody-positive patients and relative changes in antibody levels across ACPA specificities, as well as therapeutic responses and radiographic progressions.
Dr. Kastbom and his coauthors found that changes in antibody status within the first 3 months were most closely associated with radiographic progression of RA over the 2-year study period. Specifically, subjects who experienced significant decreases in anti-cVim antibodies in the first 3 months had lower rates of radiographic progression and lower total van der Heijde modified Sharp score (SHS) after 2 years than did those whose anti-cVim antibody levels remained positive (P = .012 and P = .015, respectively). Anti-cVim antibody results were also adjusted for baseline 28-joint disease activity score, baseline erosions, current smoking status, sex, and European League Against Rheumatism response at 3 months (P = .005 for SHS progression > 1 and P = .013 for SHS progression > 5, respectively).
However, no significant relationships with radiographic progression were found in the anti-cFib and anti-CEP-1 antibody seroreversions. Median antibody levels of all tested ACPAs declined during initial methotrexate therapy and after commencement of add-on therapy, but the investigators found no significant association between treatment regimen and radiographic progression.
“It is intriguing to see that our study clearly demonstrates an association between the early disappearance of specific anti-cVim antibodies and less radiological progression,” wrote Dr. Kastbom and his colleagues, adding that the findings of this study should “encourage further work to explore the prognostic potential of repeated measurements of different ACPA specificities in early RA.”
This study was financed by grants from European Union–funded FP7 projects and several Swedish institutions. Several coauthors also disclosed individual ties to various pharmaceutical companies.
The elimination of anticitrullinated vimentin antibodies during early antirheumatic therapy in rheumatoid arthritis patients may significantly increase the likelihood of positive radiographic outcomes, according to findings from a longitudinal cohort study.
“The development of serological tests for [autoantibodies recognizing citrullinated proteins (ACPA)] detection have improved the ability to diagnose rheumatoid arthritis [RA] at an early stage and to identify patients at increased risk of a severe disease course,” wrote lead author Dr. Alf Kastbom of the Karolinska Institute in Stockholm, and his associates (Ann. Rheum. Dis. 2014 Dec. 30 [doi:10.1136/annrheumdis-2014-205698]). “These clinically very useful tests do not, however, formally address the question of which specific citrullinated autoantigens are targeted.”
Dr. Kastbom and his coinvestigators longitudinally analyzed serum samples from 316 of 487 patients with early RA (symptoms < 1 year) who had participated in the Swedish Farmacotherapy (SWEFOT) trial, a randomized, nonblinded trial. These 316 patients had baseline and 3-month serum samples available that were analyzed for any antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides that were derived from vimentin (cVim), fibrinogen (cFib), and alpha-enolase (CEP-1).
For the first 3 months, all patients received methotrexate. Next, patients who were deemed “methotrexate monotherapy–inadequate responders” were subsequently randomized into cohorts that received add-on therapy with either sulfasalazine and hydroxychloroquine or infliximab. The investigators again assessed ACPA levels at 12 and 24 months after commencement of therapy in these subjects and used this 2-year follow-up period to compare proportions of antibody-positive patients and relative changes in antibody levels across ACPA specificities, as well as therapeutic responses and radiographic progressions.
Dr. Kastbom and his coauthors found that changes in antibody status within the first 3 months were most closely associated with radiographic progression of RA over the 2-year study period. Specifically, subjects who experienced significant decreases in anti-cVim antibodies in the first 3 months had lower rates of radiographic progression and lower total van der Heijde modified Sharp score (SHS) after 2 years than did those whose anti-cVim antibody levels remained positive (P = .012 and P = .015, respectively). Anti-cVim antibody results were also adjusted for baseline 28-joint disease activity score, baseline erosions, current smoking status, sex, and European League Against Rheumatism response at 3 months (P = .005 for SHS progression > 1 and P = .013 for SHS progression > 5, respectively).
However, no significant relationships with radiographic progression were found in the anti-cFib and anti-CEP-1 antibody seroreversions. Median antibody levels of all tested ACPAs declined during initial methotrexate therapy and after commencement of add-on therapy, but the investigators found no significant association between treatment regimen and radiographic progression.
“It is intriguing to see that our study clearly demonstrates an association between the early disappearance of specific anti-cVim antibodies and less radiological progression,” wrote Dr. Kastbom and his colleagues, adding that the findings of this study should “encourage further work to explore the prognostic potential of repeated measurements of different ACPA specificities in early RA.”
This study was financed by grants from European Union–funded FP7 projects and several Swedish institutions. Several coauthors also disclosed individual ties to various pharmaceutical companies.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: Early disappearance of anti-cVim antibodies can lead to better radiological outcomes in patients in the early stages of rheumatoid arthritis.
Major finding: Anti-cVim antibody seroreversion during the first 3 months of treatment was associated with significantly less 2-year radiographic progression, compared with patients who remained antibody positive.
Data source: A longitudinal cohort study of 316 participants in the randomized, nonblinded SWEFOT trial.
Disclosures: This study was financed by grants from European Union–funded FP7 projects and several Swedish institutions. Several coauthors also disclosed individual ties to various pharmaceutical companies.
Sofosbuvir and Ribavirin Critical to Preventing Posttransplantation HCV Recurrence
Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).
“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”
In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.
The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.
“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”
Continue for second study findings >>
In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.
“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.
Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”
Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.
“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”
The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.
Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).
“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”
In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.
The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.
“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”
Continue for second study findings >>
In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.
“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.
Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”
Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.
“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”
The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.
Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).
“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”
In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.
The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.
“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”
Continue for second study findings >>
In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.
“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.
Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”
Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.
“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”
The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.
FROM GASTROENTEROLOGY
Sofosbuvir and ribavirin critical to preventing posttransplantation HCV recurrence
Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).
“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”
In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.
The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.
“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”
In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.
“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.
Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”
Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.
“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”
The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.
Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).
“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”
In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.
The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.
“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”
In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.
“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.
Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”
Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.
“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”
The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.
Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).
“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”
In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.
The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.
“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”
In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.
“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.
Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”
Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.
“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”
The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.
FROM GASTROENTEROLOGY
Visible light spectrography should be used in diagnosing chronic gastrointestinal ischemia
Using visible light spectrography in the diagnosis of patients with suspected chronic gastrointestinal ischemia can lead to more accurate diagnoses, more-effective treatment regimens, and, ultimately, longer-lasting positive results, according to a new study published in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.07.012).
“Medical history and physical examination were poor predictors for the presence of CGI [chronic gastrointestinal ischemia] [but] addition of radiologic evaluation [and] functional testing by means of tonometry substantially improved the accuracy of diagnosis,” said study leader Dr. Aria Sana of Utrecht University in the Netherlands.
The authors added that “VLS [Visible light spectrography] has recently been introduced as a new minimally invasive technique to detect mucosal hypoxia by means of measurement of mucosal capillary hemoglobin oxygen saturation during endoscopy in patients clinically suspected of CGI.”
In a prospective study, Dr. Sana and her associates gathered data on 212 patients referred to their medical center between November 2008 through January 2011 for suspected CGI. Subjects underwent visualization of gastrointestinal arteries and assessments of mucosal perfusion via VLS; those found to have occlusive CGI were followed-up after a median 13 months’ time to assess their response to treatment.
Of the 212 subjects initially screened, 107 (50%) were found to have occlusive CGI. Of that population, 96 (90%) were offered treatment, of which 89 (93%) were available to provide follow-up data after the median time of 13 months.
Investigators found that 62 subjects (70% of the 89 who reported after the follow-up period) had sustained responses to treatment that they were prescribed as a result of VLS and visualization-based diagnoses. Furthermore, patients who displayed weight loss, abdominal bruit, and low corpus mucosal saturation were found most likely to respond to treatment, particularly the latter – corpus saturation level of less than 56% was “one of the strongest predictors of a positive treatment response” investigators found.
“The presence of [at least] two predictors or the absence of any predictor was of discriminative value with [greater than] 85% vs. [less than] 50% response rate, respectively, suggesting patients with a predicted response rate of < 50% should primarily be considered for conservative management,” Dr. Sana and her coinvestigators noted.
The authors disclosed no conflicts of any kind.
In this study from the Netherlands, the authors used visible light spectroscopy (VLS) to diagnose chronic gastrointestinal ischemia (CGI) and to predict its response to surgical or endoscopic treatment; a challenging task indeed. Diagnosis of CGI is difficult because the classic symptom complex of meal-precipitated abdominal pain leading to weight loss is nonspecific; asymptomatic splanchnic vascular obstruction is not uncommon in the general population with autopsy series showing significant stenosis of the celiac, superior mesenteric, and inferior mesenteric arteries of 50%, 30%, and 30%, respectively; radiologic imaging tests conventionally used to diagnose CGI evaluate only vascular anatomy and not physiologic parameters of ischemia, i.e., intracellular acidosis (which can be evaluated by balloon tonometry) nor mucosal hemoglobin oxygen saturation, which is determined by VLS.
The authors evaluated 212 patients referred for suspected CGI and in all performed radiologic imaging of the splanchnic vessels and assessment of mucosal perfusion by VLS. Obstructive CGI (OCGI)was diagnosed by a multidisciplinary team and required clinical agreement, significant stenosis of at least one splanchnic artery and mucosal ischemia as determined by VLS. OCGI was classified as single- or multivessel and patients were offered surgical or endovascular revascularization. Response to treatment was then evaluated in patients with OCGI. A total of 107 patients were diagnosed with OCGI and data on response to treatment was available in 89 with a median follow-up of 13 months. Sustained symptomatic response was seen in 62 (70%) and most strongly predicted by the presence of weight loss, an abdominal bruit, and a gastric corpus mucosal saturation level of < 56%. This is an important study because it stresses the value of a team approach to diagnosis and the use of a combination of techniques to evaluate vascular obstruction and its functional significance.
There were several shortcomings of the study, in my opinion, although these do not lessen the importance of the study’s message. Most important, the study was not blinded. Spontaneous resolution of symptoms was noted in 19 patients without OCGI and in an additional 9 patients treated with a variety of medical and surgical means. Celiac artery compression release relieved symptoms in 17 patients, although the ischemic nature of this entity is arguable. Repeat VLS was not performed in all patients. Finally, clinical follow-up was relatively short and long-term follow-up was mainly by questionnaire, leading to another source of bias. To perform fiber-optic catheter-based VLS oximetry during esophagogastroduodenoscopy in a consistent fashion is technically challenging but probably worthwhile to learn. The authors continue to shine light on this relatively dark and poorly illuminated subject matter; let it shine, let it shine, let it shine.
Dr. Lawrence J. Brandt, MACG, AGAF, FASGE, is a professor of medicine and surgery at the Albert Einstein College of Medicine, N.Y., and emeritus chief, division of gastroenterology, Montefiore Medical Center, Bronx, N.Y.
In this study from the Netherlands, the authors used visible light spectroscopy (VLS) to diagnose chronic gastrointestinal ischemia (CGI) and to predict its response to surgical or endoscopic treatment; a challenging task indeed. Diagnosis of CGI is difficult because the classic symptom complex of meal-precipitated abdominal pain leading to weight loss is nonspecific; asymptomatic splanchnic vascular obstruction is not uncommon in the general population with autopsy series showing significant stenosis of the celiac, superior mesenteric, and inferior mesenteric arteries of 50%, 30%, and 30%, respectively; radiologic imaging tests conventionally used to diagnose CGI evaluate only vascular anatomy and not physiologic parameters of ischemia, i.e., intracellular acidosis (which can be evaluated by balloon tonometry) nor mucosal hemoglobin oxygen saturation, which is determined by VLS.
The authors evaluated 212 patients referred for suspected CGI and in all performed radiologic imaging of the splanchnic vessels and assessment of mucosal perfusion by VLS. Obstructive CGI (OCGI)was diagnosed by a multidisciplinary team and required clinical agreement, significant stenosis of at least one splanchnic artery and mucosal ischemia as determined by VLS. OCGI was classified as single- or multivessel and patients were offered surgical or endovascular revascularization. Response to treatment was then evaluated in patients with OCGI. A total of 107 patients were diagnosed with OCGI and data on response to treatment was available in 89 with a median follow-up of 13 months. Sustained symptomatic response was seen in 62 (70%) and most strongly predicted by the presence of weight loss, an abdominal bruit, and a gastric corpus mucosal saturation level of < 56%. This is an important study because it stresses the value of a team approach to diagnosis and the use of a combination of techniques to evaluate vascular obstruction and its functional significance.
There were several shortcomings of the study, in my opinion, although these do not lessen the importance of the study’s message. Most important, the study was not blinded. Spontaneous resolution of symptoms was noted in 19 patients without OCGI and in an additional 9 patients treated with a variety of medical and surgical means. Celiac artery compression release relieved symptoms in 17 patients, although the ischemic nature of this entity is arguable. Repeat VLS was not performed in all patients. Finally, clinical follow-up was relatively short and long-term follow-up was mainly by questionnaire, leading to another source of bias. To perform fiber-optic catheter-based VLS oximetry during esophagogastroduodenoscopy in a consistent fashion is technically challenging but probably worthwhile to learn. The authors continue to shine light on this relatively dark and poorly illuminated subject matter; let it shine, let it shine, let it shine.
Dr. Lawrence J. Brandt, MACG, AGAF, FASGE, is a professor of medicine and surgery at the Albert Einstein College of Medicine, N.Y., and emeritus chief, division of gastroenterology, Montefiore Medical Center, Bronx, N.Y.
In this study from the Netherlands, the authors used visible light spectroscopy (VLS) to diagnose chronic gastrointestinal ischemia (CGI) and to predict its response to surgical or endoscopic treatment; a challenging task indeed. Diagnosis of CGI is difficult because the classic symptom complex of meal-precipitated abdominal pain leading to weight loss is nonspecific; asymptomatic splanchnic vascular obstruction is not uncommon in the general population with autopsy series showing significant stenosis of the celiac, superior mesenteric, and inferior mesenteric arteries of 50%, 30%, and 30%, respectively; radiologic imaging tests conventionally used to diagnose CGI evaluate only vascular anatomy and not physiologic parameters of ischemia, i.e., intracellular acidosis (which can be evaluated by balloon tonometry) nor mucosal hemoglobin oxygen saturation, which is determined by VLS.
The authors evaluated 212 patients referred for suspected CGI and in all performed radiologic imaging of the splanchnic vessels and assessment of mucosal perfusion by VLS. Obstructive CGI (OCGI)was diagnosed by a multidisciplinary team and required clinical agreement, significant stenosis of at least one splanchnic artery and mucosal ischemia as determined by VLS. OCGI was classified as single- or multivessel and patients were offered surgical or endovascular revascularization. Response to treatment was then evaluated in patients with OCGI. A total of 107 patients were diagnosed with OCGI and data on response to treatment was available in 89 with a median follow-up of 13 months. Sustained symptomatic response was seen in 62 (70%) and most strongly predicted by the presence of weight loss, an abdominal bruit, and a gastric corpus mucosal saturation level of < 56%. This is an important study because it stresses the value of a team approach to diagnosis and the use of a combination of techniques to evaluate vascular obstruction and its functional significance.
There were several shortcomings of the study, in my opinion, although these do not lessen the importance of the study’s message. Most important, the study was not blinded. Spontaneous resolution of symptoms was noted in 19 patients without OCGI and in an additional 9 patients treated with a variety of medical and surgical means. Celiac artery compression release relieved symptoms in 17 patients, although the ischemic nature of this entity is arguable. Repeat VLS was not performed in all patients. Finally, clinical follow-up was relatively short and long-term follow-up was mainly by questionnaire, leading to another source of bias. To perform fiber-optic catheter-based VLS oximetry during esophagogastroduodenoscopy in a consistent fashion is technically challenging but probably worthwhile to learn. The authors continue to shine light on this relatively dark and poorly illuminated subject matter; let it shine, let it shine, let it shine.
Dr. Lawrence J. Brandt, MACG, AGAF, FASGE, is a professor of medicine and surgery at the Albert Einstein College of Medicine, N.Y., and emeritus chief, division of gastroenterology, Montefiore Medical Center, Bronx, N.Y.
Using visible light spectrography in the diagnosis of patients with suspected chronic gastrointestinal ischemia can lead to more accurate diagnoses, more-effective treatment regimens, and, ultimately, longer-lasting positive results, according to a new study published in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.07.012).
“Medical history and physical examination were poor predictors for the presence of CGI [chronic gastrointestinal ischemia] [but] addition of radiologic evaluation [and] functional testing by means of tonometry substantially improved the accuracy of diagnosis,” said study leader Dr. Aria Sana of Utrecht University in the Netherlands.
The authors added that “VLS [Visible light spectrography] has recently been introduced as a new minimally invasive technique to detect mucosal hypoxia by means of measurement of mucosal capillary hemoglobin oxygen saturation during endoscopy in patients clinically suspected of CGI.”
In a prospective study, Dr. Sana and her associates gathered data on 212 patients referred to their medical center between November 2008 through January 2011 for suspected CGI. Subjects underwent visualization of gastrointestinal arteries and assessments of mucosal perfusion via VLS; those found to have occlusive CGI were followed-up after a median 13 months’ time to assess their response to treatment.
Of the 212 subjects initially screened, 107 (50%) were found to have occlusive CGI. Of that population, 96 (90%) were offered treatment, of which 89 (93%) were available to provide follow-up data after the median time of 13 months.
Investigators found that 62 subjects (70% of the 89 who reported after the follow-up period) had sustained responses to treatment that they were prescribed as a result of VLS and visualization-based diagnoses. Furthermore, patients who displayed weight loss, abdominal bruit, and low corpus mucosal saturation were found most likely to respond to treatment, particularly the latter – corpus saturation level of less than 56% was “one of the strongest predictors of a positive treatment response” investigators found.
“The presence of [at least] two predictors or the absence of any predictor was of discriminative value with [greater than] 85% vs. [less than] 50% response rate, respectively, suggesting patients with a predicted response rate of < 50% should primarily be considered for conservative management,” Dr. Sana and her coinvestigators noted.
The authors disclosed no conflicts of any kind.
Using visible light spectrography in the diagnosis of patients with suspected chronic gastrointestinal ischemia can lead to more accurate diagnoses, more-effective treatment regimens, and, ultimately, longer-lasting positive results, according to a new study published in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.07.012).
“Medical history and physical examination were poor predictors for the presence of CGI [chronic gastrointestinal ischemia] [but] addition of radiologic evaluation [and] functional testing by means of tonometry substantially improved the accuracy of diagnosis,” said study leader Dr. Aria Sana of Utrecht University in the Netherlands.
The authors added that “VLS [Visible light spectrography] has recently been introduced as a new minimally invasive technique to detect mucosal hypoxia by means of measurement of mucosal capillary hemoglobin oxygen saturation during endoscopy in patients clinically suspected of CGI.”
In a prospective study, Dr. Sana and her associates gathered data on 212 patients referred to their medical center between November 2008 through January 2011 for suspected CGI. Subjects underwent visualization of gastrointestinal arteries and assessments of mucosal perfusion via VLS; those found to have occlusive CGI were followed-up after a median 13 months’ time to assess their response to treatment.
Of the 212 subjects initially screened, 107 (50%) were found to have occlusive CGI. Of that population, 96 (90%) were offered treatment, of which 89 (93%) were available to provide follow-up data after the median time of 13 months.
Investigators found that 62 subjects (70% of the 89 who reported after the follow-up period) had sustained responses to treatment that they were prescribed as a result of VLS and visualization-based diagnoses. Furthermore, patients who displayed weight loss, abdominal bruit, and low corpus mucosal saturation were found most likely to respond to treatment, particularly the latter – corpus saturation level of less than 56% was “one of the strongest predictors of a positive treatment response” investigators found.
“The presence of [at least] two predictors or the absence of any predictor was of discriminative value with [greater than] 85% vs. [less than] 50% response rate, respectively, suggesting patients with a predicted response rate of < 50% should primarily be considered for conservative management,” Dr. Sana and her coinvestigators noted.
The authors disclosed no conflicts of any kind.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Diagnosis of chronic gastrointestinal ischemia (CGI) via visible light spectrography (VLS) can lead to more effective treatment methods that yield longer-term results.
Major finding: Of patients diagnosed with CGI via VLS, 70% reported sustained responses to treatment after 13 months.
Data source: A prospective study.
Disclosures: The authors reported no conflicts.
Identification of subtypes, mutations in CRC and colon cancer greatly increases survival rates
Identifying subtypes and tumor mutations in patients with colorectal and stage III colon cancer can significantly improve survival rates, according to two new studies published in the January issue of Gastroenterology (doi:10.1053/j.gastro.2014.09.038 and doi:10.1053/j.gastro.2014.09.041).
In the first study, researchers found that etiologically defined subtypes of colorectal cancer are characterized by marked differences in survival rates and confirmed the clinical importance of studying the molecular heterogeneity of the disease.
“Increasing evidence indicates that colorectal cancer (CRC) is a biologically heterogeneous disease that can develop via a number of distinct pathways involving different combinations of genetic and epigenetic changes,” wrote Amanda Phipps, Ph.D, of the University of Washington in Seattle, and her coinvestigators, adding that “the biologic distinctions between CRC subtypes resulting from different etiologic pathways may plausibly translate to differences in survival.”
Between 1998 and 2007, 2,706 participants were enrolled for this study through the population-based Seattle Colon Cancer Family Registry and followed for survival through 2012. Of those, 2,050 had tumor samples collected from them, each of which was classified into one of five subtypes based on tumor markers: type 1 (microsatellite instability [MSI] high, CpG island methylator phenotype [CIMP] positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMPpositive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI-low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS).
To analyze data, Cox regression models were used to estimate hazard ratios, 95% confidence intervals, and associations for each subtype with specific diseases and overall mortality, all of which were adjusted for age, sex, body mass, diagnosis year, and smoking history.
Results indicated that type 4 tumors were the most predominant, but subjects with type 2 tumors had the highest disease-specific mortality (hazard ratio = 2.20) and subjects with type 3 tumors also had unusually high disease-specific mortality (HR = 1.32). Type 5 tumors were associated with the lowest disease-specific mortality (HR = 0.30). Associations with overall mortality were similar to those with disease-specific mortality.
“These findings contribute to a small but growing literature supporting the significance of CRC-subtype classifications defined by combinations of these tumor markers,” the authors noted.
The second study’s results indicate that patients suffering from stage III colon cancer who have MMR-proficient tumors and mutations in BRAF (V600E) or KRAS had shorter survival times than patients whose tumors lacked these specific mutations.
“Defining [CRC] tumor subtypes based upon pathway-driven alterations has the potential to improve prognostication and guide targeted therapy,” wrote Dr. Frank Sinicrope of the Mayo Clinic in Rochester, Minn., and his associates.
Investigators collected 2,720 tumor samples from stage III cancer patients and detected mutations in BRAF (V600E) and KRAS using a polymerase chain reaction–based assay, and tumors deficient or proficient in DNA mismatch repair (MMR) via detection of MLH1, MSH2, and MSH6 proteins and methylation of the MLH1 promoter. Investigators used a separate sample of tumors, taken from 783 stage III cancer patients, to validate their findings, and employed the Cox proportional hazards model to evaluate associations between tumors and 5-year disease-free survival rates.
Tumors were divided into five subtypes, three of which were MMR proficient – those with BRAFV600E (6.9% of samples), mutations in KRAS (35%), or tumors lacking either BRAFV600E or mutations in KRAS (49%) – and two of which were MMR deficient: the sporadic type (6.8%) with BRAFV600E or hypermethylation of MLH1, and the familial type (2.6%), which lacked BRAFV600E or hypermethylation of MLH1.
The data accumulated by Dr. Sinicrope and his coinvestigators showed that more MMR-proficient tumors with BRAFV600E than MMR-proficient tumors without BRAFV600E or mutations in KRAS were proximal, high grade, N2, and prevalent in female subjects: 76% vs. 33%, 44% vs. 19%, 59% vs. 41%, and 59% vs. 42%, respectively (overall P < .0001).
Furthermore, a “significantly lower proportion” of patients having MMR-proficient tumors with BRAFV600E (HR 1.43; adjusted P = .0065) or mutant KRAS (HR 1.48; adjusted P < .0001) survived disease free for 5 years, compared with those whose MMR-proficient tumors lacked mutations in either gene.
“We found that a biomarker-based classifier can identify prognostically distinct subtypes within stage III colon cancer patients that was externally validated,” the authors wrote, adding that “taken together, our biomarker classifier provides important prognostic information in stage III colon cancers with implications for patient management.”
The investigators for both studies reported no relevant financial disclosures.
It is now recognized that colon cancer is quite heterogeneous on a genetic level, and the clinical features associated with each of these genetic subtypes are equally heterogeneous. The two current studies addressed the question of whether long-term prognosis differs among these genetic subtypes. Colon tumors were first divided into five distinct categories, based upon a panel of multiple molecular markers. One study analyzed more than 2,700 colon cancers of all stages, whereas the other examined more than 2,700 stage III tumors from a North Central Cancer Treatment Group adjuvant chemotherapy trial.
Similar patterns emerged. Tumors with the least favorable prognosis were the so-called “serrated” tumors that are DNA mismatch-repair (MMR) proficient and are positive for a BRAF mutation. Tumors with deficient MMR (MSI-H), whether sporadic or associated with Lynch syndrome, consistently exhibited the most favorable prognosis and highest rates of long-term survival.
These studies provide strong evidence that links survival with specific tumor genotypes, regardless of stage or treatment, and establish the significance of molecular genotyping for prognostic purposes. There are other important reasons to perform tumor genotyping, including the identification of unrecognized Lynch syndrome. However, the therapeutic implications of tumor genotyping remain less clear, as meaningful targeted therapies for each of the specific subgroups are still lacking. In particular, effective targeting of the BRAF oncogene in serrated tumors remains an important priority. More refined molecular classifications are likely to emerge in the future, and the opportunities to offer more precise and personalized approaches to management should increase in parallel.
Dr. Daniel C. Chung is associate professor, department of medicine, Harvard Medical School, Boston, and director, Hi-Risk Gastrointestinal Cancer Clinic, Massachusetts General Hospital, also in Boston. He had no conflicts of interest.
It is now recognized that colon cancer is quite heterogeneous on a genetic level, and the clinical features associated with each of these genetic subtypes are equally heterogeneous. The two current studies addressed the question of whether long-term prognosis differs among these genetic subtypes. Colon tumors were first divided into five distinct categories, based upon a panel of multiple molecular markers. One study analyzed more than 2,700 colon cancers of all stages, whereas the other examined more than 2,700 stage III tumors from a North Central Cancer Treatment Group adjuvant chemotherapy trial.
Similar patterns emerged. Tumors with the least favorable prognosis were the so-called “serrated” tumors that are DNA mismatch-repair (MMR) proficient and are positive for a BRAF mutation. Tumors with deficient MMR (MSI-H), whether sporadic or associated with Lynch syndrome, consistently exhibited the most favorable prognosis and highest rates of long-term survival.
These studies provide strong evidence that links survival with specific tumor genotypes, regardless of stage or treatment, and establish the significance of molecular genotyping for prognostic purposes. There are other important reasons to perform tumor genotyping, including the identification of unrecognized Lynch syndrome. However, the therapeutic implications of tumor genotyping remain less clear, as meaningful targeted therapies for each of the specific subgroups are still lacking. In particular, effective targeting of the BRAF oncogene in serrated tumors remains an important priority. More refined molecular classifications are likely to emerge in the future, and the opportunities to offer more precise and personalized approaches to management should increase in parallel.
Dr. Daniel C. Chung is associate professor, department of medicine, Harvard Medical School, Boston, and director, Hi-Risk Gastrointestinal Cancer Clinic, Massachusetts General Hospital, also in Boston. He had no conflicts of interest.
It is now recognized that colon cancer is quite heterogeneous on a genetic level, and the clinical features associated with each of these genetic subtypes are equally heterogeneous. The two current studies addressed the question of whether long-term prognosis differs among these genetic subtypes. Colon tumors were first divided into five distinct categories, based upon a panel of multiple molecular markers. One study analyzed more than 2,700 colon cancers of all stages, whereas the other examined more than 2,700 stage III tumors from a North Central Cancer Treatment Group adjuvant chemotherapy trial.
Similar patterns emerged. Tumors with the least favorable prognosis were the so-called “serrated” tumors that are DNA mismatch-repair (MMR) proficient and are positive for a BRAF mutation. Tumors with deficient MMR (MSI-H), whether sporadic or associated with Lynch syndrome, consistently exhibited the most favorable prognosis and highest rates of long-term survival.
These studies provide strong evidence that links survival with specific tumor genotypes, regardless of stage or treatment, and establish the significance of molecular genotyping for prognostic purposes. There are other important reasons to perform tumor genotyping, including the identification of unrecognized Lynch syndrome. However, the therapeutic implications of tumor genotyping remain less clear, as meaningful targeted therapies for each of the specific subgroups are still lacking. In particular, effective targeting of the BRAF oncogene in serrated tumors remains an important priority. More refined molecular classifications are likely to emerge in the future, and the opportunities to offer more precise and personalized approaches to management should increase in parallel.
Dr. Daniel C. Chung is associate professor, department of medicine, Harvard Medical School, Boston, and director, Hi-Risk Gastrointestinal Cancer Clinic, Massachusetts General Hospital, also in Boston. He had no conflicts of interest.
Identifying subtypes and tumor mutations in patients with colorectal and stage III colon cancer can significantly improve survival rates, according to two new studies published in the January issue of Gastroenterology (doi:10.1053/j.gastro.2014.09.038 and doi:10.1053/j.gastro.2014.09.041).
In the first study, researchers found that etiologically defined subtypes of colorectal cancer are characterized by marked differences in survival rates and confirmed the clinical importance of studying the molecular heterogeneity of the disease.
“Increasing evidence indicates that colorectal cancer (CRC) is a biologically heterogeneous disease that can develop via a number of distinct pathways involving different combinations of genetic and epigenetic changes,” wrote Amanda Phipps, Ph.D, of the University of Washington in Seattle, and her coinvestigators, adding that “the biologic distinctions between CRC subtypes resulting from different etiologic pathways may plausibly translate to differences in survival.”
Between 1998 and 2007, 2,706 participants were enrolled for this study through the population-based Seattle Colon Cancer Family Registry and followed for survival through 2012. Of those, 2,050 had tumor samples collected from them, each of which was classified into one of five subtypes based on tumor markers: type 1 (microsatellite instability [MSI] high, CpG island methylator phenotype [CIMP] positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMPpositive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI-low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS).
To analyze data, Cox regression models were used to estimate hazard ratios, 95% confidence intervals, and associations for each subtype with specific diseases and overall mortality, all of which were adjusted for age, sex, body mass, diagnosis year, and smoking history.
Results indicated that type 4 tumors were the most predominant, but subjects with type 2 tumors had the highest disease-specific mortality (hazard ratio = 2.20) and subjects with type 3 tumors also had unusually high disease-specific mortality (HR = 1.32). Type 5 tumors were associated with the lowest disease-specific mortality (HR = 0.30). Associations with overall mortality were similar to those with disease-specific mortality.
“These findings contribute to a small but growing literature supporting the significance of CRC-subtype classifications defined by combinations of these tumor markers,” the authors noted.
The second study’s results indicate that patients suffering from stage III colon cancer who have MMR-proficient tumors and mutations in BRAF (V600E) or KRAS had shorter survival times than patients whose tumors lacked these specific mutations.
“Defining [CRC] tumor subtypes based upon pathway-driven alterations has the potential to improve prognostication and guide targeted therapy,” wrote Dr. Frank Sinicrope of the Mayo Clinic in Rochester, Minn., and his associates.
Investigators collected 2,720 tumor samples from stage III cancer patients and detected mutations in BRAF (V600E) and KRAS using a polymerase chain reaction–based assay, and tumors deficient or proficient in DNA mismatch repair (MMR) via detection of MLH1, MSH2, and MSH6 proteins and methylation of the MLH1 promoter. Investigators used a separate sample of tumors, taken from 783 stage III cancer patients, to validate their findings, and employed the Cox proportional hazards model to evaluate associations between tumors and 5-year disease-free survival rates.
Tumors were divided into five subtypes, three of which were MMR proficient – those with BRAFV600E (6.9% of samples), mutations in KRAS (35%), or tumors lacking either BRAFV600E or mutations in KRAS (49%) – and two of which were MMR deficient: the sporadic type (6.8%) with BRAFV600E or hypermethylation of MLH1, and the familial type (2.6%), which lacked BRAFV600E or hypermethylation of MLH1.
The data accumulated by Dr. Sinicrope and his coinvestigators showed that more MMR-proficient tumors with BRAFV600E than MMR-proficient tumors without BRAFV600E or mutations in KRAS were proximal, high grade, N2, and prevalent in female subjects: 76% vs. 33%, 44% vs. 19%, 59% vs. 41%, and 59% vs. 42%, respectively (overall P < .0001).
Furthermore, a “significantly lower proportion” of patients having MMR-proficient tumors with BRAFV600E (HR 1.43; adjusted P = .0065) or mutant KRAS (HR 1.48; adjusted P < .0001) survived disease free for 5 years, compared with those whose MMR-proficient tumors lacked mutations in either gene.
“We found that a biomarker-based classifier can identify prognostically distinct subtypes within stage III colon cancer patients that was externally validated,” the authors wrote, adding that “taken together, our biomarker classifier provides important prognostic information in stage III colon cancers with implications for patient management.”
The investigators for both studies reported no relevant financial disclosures.
Identifying subtypes and tumor mutations in patients with colorectal and stage III colon cancer can significantly improve survival rates, according to two new studies published in the January issue of Gastroenterology (doi:10.1053/j.gastro.2014.09.038 and doi:10.1053/j.gastro.2014.09.041).
In the first study, researchers found that etiologically defined subtypes of colorectal cancer are characterized by marked differences in survival rates and confirmed the clinical importance of studying the molecular heterogeneity of the disease.
“Increasing evidence indicates that colorectal cancer (CRC) is a biologically heterogeneous disease that can develop via a number of distinct pathways involving different combinations of genetic and epigenetic changes,” wrote Amanda Phipps, Ph.D, of the University of Washington in Seattle, and her coinvestigators, adding that “the biologic distinctions between CRC subtypes resulting from different etiologic pathways may plausibly translate to differences in survival.”
Between 1998 and 2007, 2,706 participants were enrolled for this study through the population-based Seattle Colon Cancer Family Registry and followed for survival through 2012. Of those, 2,050 had tumor samples collected from them, each of which was classified into one of five subtypes based on tumor markers: type 1 (microsatellite instability [MSI] high, CpG island methylator phenotype [CIMP] positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMPpositive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI-low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS).
To analyze data, Cox regression models were used to estimate hazard ratios, 95% confidence intervals, and associations for each subtype with specific diseases and overall mortality, all of which were adjusted for age, sex, body mass, diagnosis year, and smoking history.
Results indicated that type 4 tumors were the most predominant, but subjects with type 2 tumors had the highest disease-specific mortality (hazard ratio = 2.20) and subjects with type 3 tumors also had unusually high disease-specific mortality (HR = 1.32). Type 5 tumors were associated with the lowest disease-specific mortality (HR = 0.30). Associations with overall mortality were similar to those with disease-specific mortality.
“These findings contribute to a small but growing literature supporting the significance of CRC-subtype classifications defined by combinations of these tumor markers,” the authors noted.
The second study’s results indicate that patients suffering from stage III colon cancer who have MMR-proficient tumors and mutations in BRAF (V600E) or KRAS had shorter survival times than patients whose tumors lacked these specific mutations.
“Defining [CRC] tumor subtypes based upon pathway-driven alterations has the potential to improve prognostication and guide targeted therapy,” wrote Dr. Frank Sinicrope of the Mayo Clinic in Rochester, Minn., and his associates.
Investigators collected 2,720 tumor samples from stage III cancer patients and detected mutations in BRAF (V600E) and KRAS using a polymerase chain reaction–based assay, and tumors deficient or proficient in DNA mismatch repair (MMR) via detection of MLH1, MSH2, and MSH6 proteins and methylation of the MLH1 promoter. Investigators used a separate sample of tumors, taken from 783 stage III cancer patients, to validate their findings, and employed the Cox proportional hazards model to evaluate associations between tumors and 5-year disease-free survival rates.
Tumors were divided into five subtypes, three of which were MMR proficient – those with BRAFV600E (6.9% of samples), mutations in KRAS (35%), or tumors lacking either BRAFV600E or mutations in KRAS (49%) – and two of which were MMR deficient: the sporadic type (6.8%) with BRAFV600E or hypermethylation of MLH1, and the familial type (2.6%), which lacked BRAFV600E or hypermethylation of MLH1.
The data accumulated by Dr. Sinicrope and his coinvestigators showed that more MMR-proficient tumors with BRAFV600E than MMR-proficient tumors without BRAFV600E or mutations in KRAS were proximal, high grade, N2, and prevalent in female subjects: 76% vs. 33%, 44% vs. 19%, 59% vs. 41%, and 59% vs. 42%, respectively (overall P < .0001).
Furthermore, a “significantly lower proportion” of patients having MMR-proficient tumors with BRAFV600E (HR 1.43; adjusted P = .0065) or mutant KRAS (HR 1.48; adjusted P < .0001) survived disease free for 5 years, compared with those whose MMR-proficient tumors lacked mutations in either gene.
“We found that a biomarker-based classifier can identify prognostically distinct subtypes within stage III colon cancer patients that was externally validated,” the authors wrote, adding that “taken together, our biomarker classifier provides important prognostic information in stage III colon cancers with implications for patient management.”
The investigators for both studies reported no relevant financial disclosures.
FROM GASTROENTEROLOGY
Clinical factors associated with IBD can increase risk of CMV disease
Specific clinical features present in patients with inflammatory bowel disease can significantly increase their risks for developing cytomegalovirus (CMV) disease, according to a study published in Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2014.05.026).
Inflammatory bowel disease (IBD) “is an ideal condition for viral reactivation because of the frequent use of immunosuppressive therapy and the virus’s tropism for inflamed mucosa. The association appears greatest with ulcerative colitis (UC) refractory to corticosteroids (CS) but has also been reported with Crohn’s disease (CD),” wrote Dr. Jeffrey D. McCurdy of the Mayo Clinic, Rochester, Minn., and his coauthors.
In a retrospective, case-controlled study, the investigators examined 1,111 patients between January 2005 and December 2011. Among these patients, 68 (6% of original population) were diagnosed with cytomegalovirus (CMV) disease; 66% (45 patients) had ulcerative colitis, 31% (21 patients) had Crohn’s disease, and 3% (2 patients) were diagnosed with unclassified IBD. Each of these patients were matched to 3 other subjects diagnosed with IBD and suspected CMV disease, who represented the study’s controls.
Patients were classified into groups of initial IBD assessment, symptomatic disease without therapeutic escalation, refractory disease, or “other,” which was used for subjects with “inadequate records, minimal clinical symptoms but moderate or severe endoscopic disease, or patients who did not meet the criteria for refractory disease.” Refractory disease classifications were for subjects who displayed little to no improvement in symptoms after 14 days of oral corticosteroids (CS), 7 days of intravenous CS, 2 induction doses of a tumor necrosis factor (TNF) antagonist, or escalated dosing of a TNF antagonist.
Preset clinical and endoscopic definitions were used to score each of the subjects. Medication exposure for TNF antagonists was considered positive if taken within 2 months of CMV disease diagnosis, and considered positive for methotrexate, thiopurines, (CS), and mesalamine when taken within 1 month. Investigators also grouped thiopurines and methotrexate together as immunomodulators (IM) for the purposes of simplifying data analysis.
The authors found that subjects with medically refractory IBD (odds ratio [OR], 3.69; P < .001) or endoscopic ulcers (OR, 3.06; P < .001), and those who received CS (OR, 2.95; P < .001) or IM (OR, 1.86; P = .030) – but did not receive TNF antagonists (OR, 1.30; P = .376) – were more likely to have CMV disease than were patients who had IBD but did not have these other clinical features. Investigators also ran a multivariable model, which showed that refractory disease classification, treatment with IM, and age greater than 30 were “independently associated with CMV disease.”
“The current risk model should help modify the current recommendations that apply only to hospitalized patients with acute, severe UC by reducing unnecessary, invasive testing in hospitalized patients and identifying high-risk ambulatory patients who may not have otherwise been considered for testing,” the authors wrote.
Dr. McCurdy and his coauthors reported no financial disclosures.
Specific clinical features present in patients with inflammatory bowel disease can significantly increase their risks for developing cytomegalovirus (CMV) disease, according to a study published in Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2014.05.026).
Inflammatory bowel disease (IBD) “is an ideal condition for viral reactivation because of the frequent use of immunosuppressive therapy and the virus’s tropism for inflamed mucosa. The association appears greatest with ulcerative colitis (UC) refractory to corticosteroids (CS) but has also been reported with Crohn’s disease (CD),” wrote Dr. Jeffrey D. McCurdy of the Mayo Clinic, Rochester, Minn., and his coauthors.
In a retrospective, case-controlled study, the investigators examined 1,111 patients between January 2005 and December 2011. Among these patients, 68 (6% of original population) were diagnosed with cytomegalovirus (CMV) disease; 66% (45 patients) had ulcerative colitis, 31% (21 patients) had Crohn’s disease, and 3% (2 patients) were diagnosed with unclassified IBD. Each of these patients were matched to 3 other subjects diagnosed with IBD and suspected CMV disease, who represented the study’s controls.
Patients were classified into groups of initial IBD assessment, symptomatic disease without therapeutic escalation, refractory disease, or “other,” which was used for subjects with “inadequate records, minimal clinical symptoms but moderate or severe endoscopic disease, or patients who did not meet the criteria for refractory disease.” Refractory disease classifications were for subjects who displayed little to no improvement in symptoms after 14 days of oral corticosteroids (CS), 7 days of intravenous CS, 2 induction doses of a tumor necrosis factor (TNF) antagonist, or escalated dosing of a TNF antagonist.
Preset clinical and endoscopic definitions were used to score each of the subjects. Medication exposure for TNF antagonists was considered positive if taken within 2 months of CMV disease diagnosis, and considered positive for methotrexate, thiopurines, (CS), and mesalamine when taken within 1 month. Investigators also grouped thiopurines and methotrexate together as immunomodulators (IM) for the purposes of simplifying data analysis.
The authors found that subjects with medically refractory IBD (odds ratio [OR], 3.69; P < .001) or endoscopic ulcers (OR, 3.06; P < .001), and those who received CS (OR, 2.95; P < .001) or IM (OR, 1.86; P = .030) – but did not receive TNF antagonists (OR, 1.30; P = .376) – were more likely to have CMV disease than were patients who had IBD but did not have these other clinical features. Investigators also ran a multivariable model, which showed that refractory disease classification, treatment with IM, and age greater than 30 were “independently associated with CMV disease.”
“The current risk model should help modify the current recommendations that apply only to hospitalized patients with acute, severe UC by reducing unnecessary, invasive testing in hospitalized patients and identifying high-risk ambulatory patients who may not have otherwise been considered for testing,” the authors wrote.
Dr. McCurdy and his coauthors reported no financial disclosures.
Specific clinical features present in patients with inflammatory bowel disease can significantly increase their risks for developing cytomegalovirus (CMV) disease, according to a study published in Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2014.05.026).
Inflammatory bowel disease (IBD) “is an ideal condition for viral reactivation because of the frequent use of immunosuppressive therapy and the virus’s tropism for inflamed mucosa. The association appears greatest with ulcerative colitis (UC) refractory to corticosteroids (CS) but has also been reported with Crohn’s disease (CD),” wrote Dr. Jeffrey D. McCurdy of the Mayo Clinic, Rochester, Minn., and his coauthors.
In a retrospective, case-controlled study, the investigators examined 1,111 patients between January 2005 and December 2011. Among these patients, 68 (6% of original population) were diagnosed with cytomegalovirus (CMV) disease; 66% (45 patients) had ulcerative colitis, 31% (21 patients) had Crohn’s disease, and 3% (2 patients) were diagnosed with unclassified IBD. Each of these patients were matched to 3 other subjects diagnosed with IBD and suspected CMV disease, who represented the study’s controls.
Patients were classified into groups of initial IBD assessment, symptomatic disease without therapeutic escalation, refractory disease, or “other,” which was used for subjects with “inadequate records, minimal clinical symptoms but moderate or severe endoscopic disease, or patients who did not meet the criteria for refractory disease.” Refractory disease classifications were for subjects who displayed little to no improvement in symptoms after 14 days of oral corticosteroids (CS), 7 days of intravenous CS, 2 induction doses of a tumor necrosis factor (TNF) antagonist, or escalated dosing of a TNF antagonist.
Preset clinical and endoscopic definitions were used to score each of the subjects. Medication exposure for TNF antagonists was considered positive if taken within 2 months of CMV disease diagnosis, and considered positive for methotrexate, thiopurines, (CS), and mesalamine when taken within 1 month. Investigators also grouped thiopurines and methotrexate together as immunomodulators (IM) for the purposes of simplifying data analysis.
The authors found that subjects with medically refractory IBD (odds ratio [OR], 3.69; P < .001) or endoscopic ulcers (OR, 3.06; P < .001), and those who received CS (OR, 2.95; P < .001) or IM (OR, 1.86; P = .030) – but did not receive TNF antagonists (OR, 1.30; P = .376) – were more likely to have CMV disease than were patients who had IBD but did not have these other clinical features. Investigators also ran a multivariable model, which showed that refractory disease classification, treatment with IM, and age greater than 30 were “independently associated with CMV disease.”
“The current risk model should help modify the current recommendations that apply only to hospitalized patients with acute, severe UC by reducing unnecessary, invasive testing in hospitalized patients and identifying high-risk ambulatory patients who may not have otherwise been considered for testing,” the authors wrote.
Dr. McCurdy and his coauthors reported no financial disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Patients with inflammatory bowel disease who have other specific clinical features are at significantly higher risk for cytomegalovirus disease.
Major finding: Patients with medically refractory IBD (OR, 3.69; P < .001) or endoscopic ulcers (OR, 3.06; P < .001) and those treated with corticosteroids (OR, 2.95; P < .001) or immunomodulators (OR, 1.86; P = .030) but not tumor necrosis factor antagonists (OR, 1.30; P = .376) were more likely to have CMV disease than were patients with IBD without these features.
Data source: Retrospective, case-controlled study.
Disclosures: The authors reported no financial conflicts of interest.
Link Between Early Exposure to Acetaminophen and Childhood Asthma Found Weak, Overstated
The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.
In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I2 = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.
Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I2 = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I2 = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).
The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”
The authors reported no relevant financial conflicts of interest.
The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.
In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I2 = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.
Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I2 = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I2 = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).
The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”
The authors reported no relevant financial conflicts of interest.
The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.
In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I2 = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.
Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I2 = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I2 = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).
The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”
The authors reported no relevant financial conflicts of interest.
FDA Approves Topical Ivermectin for Rosacea
The Food and Drug Administration has approved a topical formulation of ivermectin for the once-daily treatment of inflammatory lesions related to rosacea. The drug will be marketed as Soolantra by Galderma Laboratories.
Ivermectin 1% cream was found to be safe and effective for patients with moderate to severe papulopustular rosacea in two identical phase III, multicenter, randomized, double-blind, 12-week, vehicle-controlled, parallel-group studies led by Dr. Linda Stein Gold, director of dermatology clinical research and a division head of dermatology at the Henry Ford Hospital in Detroit.
In both studies, a total of 910 patients were randomized 2:1 to receive ivermectin 1% cream or a control cream once daily. The two coprimary endpoints were the percentage of patients who achieved a “clear” or “almost clear” score on the Investigator’s Global Assessment (IGA) scale at week 12, and the change in inflammatory lesion counts from baseline to week 12. The secondary efficacy endpoint assessment was the percentage change in inflammatory lesion count from baseline to week 12. The researchers also assessed safety endpoints by examining adverse events.
The mean age of patients was 50 years, 96% were white, and 67% were women. Patients had about 30 lesions each; 76%-82% were classified as having moderate rosacea based on IGA score, and the rest had severe disease. More than 90% of patients in each arm completed the study through week 12.
At week 12 in both studies, a significantly higher percentage of patients in the treatment group achieved treatment success, compared with those in the control group (38%-40% vs. 12%-19%, respectively; P less than .001). That difference was seen as early as week 4. Fewer treatment-related adverse events were reported in the ivermectin group, compared with the control group (3.4% vs. 7.2%, respectively)
In a separate head-to-head study comparing ivermectin 1% cream with metronidazole 0.75% topical cream, investigators also found that the former was more effective at treating rosacea.
“Rosacea is a common and challenging condition to manage as it tends to vary from patient to patient, often requiring a tailored approach. For that reason, we are always looking for innovative new treatments,” Dr. Stein Gold said in a statement. “While some rosacea treatments for the common bumps and pimples of the condition may take more than 4 weeks to show effect, Soolantra Cream may provide initial results as early as week 2.”
Dr. Stein Gold is a consultant for Galderma.
Doug Brunk contributed to this report.
The Food and Drug Administration has approved a topical formulation of ivermectin for the once-daily treatment of inflammatory lesions related to rosacea. The drug will be marketed as Soolantra by Galderma Laboratories.
Ivermectin 1% cream was found to be safe and effective for patients with moderate to severe papulopustular rosacea in two identical phase III, multicenter, randomized, double-blind, 12-week, vehicle-controlled, parallel-group studies led by Dr. Linda Stein Gold, director of dermatology clinical research and a division head of dermatology at the Henry Ford Hospital in Detroit.
In both studies, a total of 910 patients were randomized 2:1 to receive ivermectin 1% cream or a control cream once daily. The two coprimary endpoints were the percentage of patients who achieved a “clear” or “almost clear” score on the Investigator’s Global Assessment (IGA) scale at week 12, and the change in inflammatory lesion counts from baseline to week 12. The secondary efficacy endpoint assessment was the percentage change in inflammatory lesion count from baseline to week 12. The researchers also assessed safety endpoints by examining adverse events.
The mean age of patients was 50 years, 96% were white, and 67% were women. Patients had about 30 lesions each; 76%-82% were classified as having moderate rosacea based on IGA score, and the rest had severe disease. More than 90% of patients in each arm completed the study through week 12.
At week 12 in both studies, a significantly higher percentage of patients in the treatment group achieved treatment success, compared with those in the control group (38%-40% vs. 12%-19%, respectively; P less than .001). That difference was seen as early as week 4. Fewer treatment-related adverse events were reported in the ivermectin group, compared with the control group (3.4% vs. 7.2%, respectively)
In a separate head-to-head study comparing ivermectin 1% cream with metronidazole 0.75% topical cream, investigators also found that the former was more effective at treating rosacea.
“Rosacea is a common and challenging condition to manage as it tends to vary from patient to patient, often requiring a tailored approach. For that reason, we are always looking for innovative new treatments,” Dr. Stein Gold said in a statement. “While some rosacea treatments for the common bumps and pimples of the condition may take more than 4 weeks to show effect, Soolantra Cream may provide initial results as early as week 2.”
Dr. Stein Gold is a consultant for Galderma.
Doug Brunk contributed to this report.
The Food and Drug Administration has approved a topical formulation of ivermectin for the once-daily treatment of inflammatory lesions related to rosacea. The drug will be marketed as Soolantra by Galderma Laboratories.
Ivermectin 1% cream was found to be safe and effective for patients with moderate to severe papulopustular rosacea in two identical phase III, multicenter, randomized, double-blind, 12-week, vehicle-controlled, parallel-group studies led by Dr. Linda Stein Gold, director of dermatology clinical research and a division head of dermatology at the Henry Ford Hospital in Detroit.
In both studies, a total of 910 patients were randomized 2:1 to receive ivermectin 1% cream or a control cream once daily. The two coprimary endpoints were the percentage of patients who achieved a “clear” or “almost clear” score on the Investigator’s Global Assessment (IGA) scale at week 12, and the change in inflammatory lesion counts from baseline to week 12. The secondary efficacy endpoint assessment was the percentage change in inflammatory lesion count from baseline to week 12. The researchers also assessed safety endpoints by examining adverse events.
The mean age of patients was 50 years, 96% were white, and 67% were women. Patients had about 30 lesions each; 76%-82% were classified as having moderate rosacea based on IGA score, and the rest had severe disease. More than 90% of patients in each arm completed the study through week 12.
At week 12 in both studies, a significantly higher percentage of patients in the treatment group achieved treatment success, compared with those in the control group (38%-40% vs. 12%-19%, respectively; P less than .001). That difference was seen as early as week 4. Fewer treatment-related adverse events were reported in the ivermectin group, compared with the control group (3.4% vs. 7.2%, respectively)
In a separate head-to-head study comparing ivermectin 1% cream with metronidazole 0.75% topical cream, investigators also found that the former was more effective at treating rosacea.
“Rosacea is a common and challenging condition to manage as it tends to vary from patient to patient, often requiring a tailored approach. For that reason, we are always looking for innovative new treatments,” Dr. Stein Gold said in a statement. “While some rosacea treatments for the common bumps and pimples of the condition may take more than 4 weeks to show effect, Soolantra Cream may provide initial results as early as week 2.”
Dr. Stein Gold is a consultant for Galderma.
Doug Brunk contributed to this report.
