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High cholesterol predicts RA in women
High serum cholesterol levels predicted rheumatoid arthritis in women, but not in men, report Dr. Carl Turesson of the department of clinical sciences at Lund (Sweden) University and his associates.
A study of 290 patients (151 men, 139 women), who participated in the Malmö Preventive Medicine Program health survey and were subsequently diagnosed with rheumatoid arthritis, found that the women had higher total cholesterol levels at baseline, compared with controls (odds ratio, 1.54; 95% confidence interval, 1.22-1.94). The association remained statistically significant when adjusted for smoking and a history of early menopause, Dr. Turesson and his colleagues reported.
Cholesterol did not significantly affect risk of RA in men (OR, 1.03; 95 % CI, 0.83-1.26). Triglycerides were not a risk factor in men or women, the authors wrote.
The findings “suggest hormone-related metabolic pathways in the early pathogenesis of RA and may have implications for disease prevention and CVD risk management,” the investigators said in the report.
Read the full study in Arthritis Research and Therapy.
High serum cholesterol levels predicted rheumatoid arthritis in women, but not in men, report Dr. Carl Turesson of the department of clinical sciences at Lund (Sweden) University and his associates.
A study of 290 patients (151 men, 139 women), who participated in the Malmö Preventive Medicine Program health survey and were subsequently diagnosed with rheumatoid arthritis, found that the women had higher total cholesterol levels at baseline, compared with controls (odds ratio, 1.54; 95% confidence interval, 1.22-1.94). The association remained statistically significant when adjusted for smoking and a history of early menopause, Dr. Turesson and his colleagues reported.
Cholesterol did not significantly affect risk of RA in men (OR, 1.03; 95 % CI, 0.83-1.26). Triglycerides were not a risk factor in men or women, the authors wrote.
The findings “suggest hormone-related metabolic pathways in the early pathogenesis of RA and may have implications for disease prevention and CVD risk management,” the investigators said in the report.
Read the full study in Arthritis Research and Therapy.
High serum cholesterol levels predicted rheumatoid arthritis in women, but not in men, report Dr. Carl Turesson of the department of clinical sciences at Lund (Sweden) University and his associates.
A study of 290 patients (151 men, 139 women), who participated in the Malmö Preventive Medicine Program health survey and were subsequently diagnosed with rheumatoid arthritis, found that the women had higher total cholesterol levels at baseline, compared with controls (odds ratio, 1.54; 95% confidence interval, 1.22-1.94). The association remained statistically significant when adjusted for smoking and a history of early menopause, Dr. Turesson and his colleagues reported.
Cholesterol did not significantly affect risk of RA in men (OR, 1.03; 95 % CI, 0.83-1.26). Triglycerides were not a risk factor in men or women, the authors wrote.
The findings “suggest hormone-related metabolic pathways in the early pathogenesis of RA and may have implications for disease prevention and CVD risk management,” the investigators said in the report.
Read the full study in Arthritis Research and Therapy.
Switching to rituximab more efficacious than switching anti-TNF agents
Switching to rituximab may be more efficacious than switching anti–tumor necrosis factor agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents, data from the observational Corrona registry show.
In an adjusted analyses of two drug exposure cohorts categorized using propensity scores, patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent, reported Dr. Leslie Harrold of the University of Massachusetts, Worcester, and associates. However, this finding was not statistically significant in patients who fell outside the area of common support (trimmed population), the authors noted (Arthritis Res Ther. 2015;17:256).
Patients treated with rituximab also were more likely to achieve the study’s secondary outcomes of modified American College of Rheumatology (mACR) 20 and mACR 50 responses (trimmed population only) and demonstrate clinically meaningful improvement in modified Health Assessment Questionnaire scores than were those treated with a subsequent anti-TNF.
Overall, 265 rituximab users and 737 patients on anti-TNF agents were included in the analysis. Approximately 16.2% of rituximab users and 29.4% of users of anti-TNF agents switched to another biologic during the study period.
An analysis of safety events over the 12-month study showed the rate of new adverse events per 100 patient years was similar between groups.
The results of the study reinforce important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent and expand upon the findings with a rigorous evaluation of the comparative safety of these two drug classes, the study authors said. “This is important because patients and the rheumatologists treating them need a comprehensive evaluation of the benefit-risk profiles of different biologic agents to optimize decision making,” they wrote.
“Taken together, these results suggest that in a clinical practice, rituximab may be more efficacious than a subsequent anti-TNF agent in patients with moderately active to severely active RA and prior exposure to anti-TNF agents,” they concluded.
Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.
Switching to rituximab may be more efficacious than switching anti–tumor necrosis factor agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents, data from the observational Corrona registry show.
In an adjusted analyses of two drug exposure cohorts categorized using propensity scores, patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent, reported Dr. Leslie Harrold of the University of Massachusetts, Worcester, and associates. However, this finding was not statistically significant in patients who fell outside the area of common support (trimmed population), the authors noted (Arthritis Res Ther. 2015;17:256).
Patients treated with rituximab also were more likely to achieve the study’s secondary outcomes of modified American College of Rheumatology (mACR) 20 and mACR 50 responses (trimmed population only) and demonstrate clinically meaningful improvement in modified Health Assessment Questionnaire scores than were those treated with a subsequent anti-TNF.
Overall, 265 rituximab users and 737 patients on anti-TNF agents were included in the analysis. Approximately 16.2% of rituximab users and 29.4% of users of anti-TNF agents switched to another biologic during the study period.
An analysis of safety events over the 12-month study showed the rate of new adverse events per 100 patient years was similar between groups.
The results of the study reinforce important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent and expand upon the findings with a rigorous evaluation of the comparative safety of these two drug classes, the study authors said. “This is important because patients and the rheumatologists treating them need a comprehensive evaluation of the benefit-risk profiles of different biologic agents to optimize decision making,” they wrote.
“Taken together, these results suggest that in a clinical practice, rituximab may be more efficacious than a subsequent anti-TNF agent in patients with moderately active to severely active RA and prior exposure to anti-TNF agents,” they concluded.
Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.
Switching to rituximab may be more efficacious than switching anti–tumor necrosis factor agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents, data from the observational Corrona registry show.
In an adjusted analyses of two drug exposure cohorts categorized using propensity scores, patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent, reported Dr. Leslie Harrold of the University of Massachusetts, Worcester, and associates. However, this finding was not statistically significant in patients who fell outside the area of common support (trimmed population), the authors noted (Arthritis Res Ther. 2015;17:256).
Patients treated with rituximab also were more likely to achieve the study’s secondary outcomes of modified American College of Rheumatology (mACR) 20 and mACR 50 responses (trimmed population only) and demonstrate clinically meaningful improvement in modified Health Assessment Questionnaire scores than were those treated with a subsequent anti-TNF.
Overall, 265 rituximab users and 737 patients on anti-TNF agents were included in the analysis. Approximately 16.2% of rituximab users and 29.4% of users of anti-TNF agents switched to another biologic during the study period.
An analysis of safety events over the 12-month study showed the rate of new adverse events per 100 patient years was similar between groups.
The results of the study reinforce important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent and expand upon the findings with a rigorous evaluation of the comparative safety of these two drug classes, the study authors said. “This is important because patients and the rheumatologists treating them need a comprehensive evaluation of the benefit-risk profiles of different biologic agents to optimize decision making,” they wrote.
“Taken together, these results suggest that in a clinical practice, rituximab may be more efficacious than a subsequent anti-TNF agent in patients with moderately active to severely active RA and prior exposure to anti-TNF agents,” they concluded.
Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.
FROM ARTHRITIS RESEARCH & THERAPY
Key clinical point: Switching to rituximab may be more efficacious than switching anti-TNF agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents.
Major finding: Patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent.
Data source: Patients with RA from the Corrona registry who initiated rituximab or switched anti-TNF agents on or after Feb. 28, 2006.
Disclosures: Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.
Three-month time point critical in T2T
Three months marks a critical time point that determines whether a rheumatoid arthritis patient will reach a treatment target at 6 months, according to results of a study published in Annals of the Rheumatic Diseases.
Dr. Daniel Aletaha of the Medical University of Vienna and his associates performed a pooled analysis of clinical data from RA trials in the last decade. They found that, regardless of the starting point, 6-month success rates were clearly related to disease activity state reached at 3 months, and not so much to the number of disease activity categories improved.
The results show that a response at 3 months can be used as a decision criterion in two clinical situations. Failure to achieve minor responses (for example, ACR 20, Simplified Disease Activity Index [SDAI] 50) at the 3-month mark had the potential to almost rule out successfully reaching the target at 6 months, the investigators wrote (Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2015-208324).
Conversely, achievement of major response definitions at 3 months (for example, ACR 70, SDAI 85%) can reliably predict achievement of a good state at 6 months.
“It is also obvious therefore that for many patients in the gray zone between these response levels, the prediction may be less solid, and may – to a greater extent – rest on the physician’s decision,” they wrote.
The findings were in line with updated treat-to-target (T2T) recommendations that suggest a goal of significant improvement at 3 months and attainment of the treatment target at 6 months, they added.
The study results showed that in order to be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI/Clinical Disease Activity Index needed to be observed at 3 months.
Patients who did not achieve the (minor) SDAI 50% response level had very low negative likelihood ratios of 0.28 for low disease activity and 0.07 for remission at 6 months. Patients who achieved the (major) SDAI 85% response had substantial positive likelihood ratios of 9.2 for reaching low disease activity and 6.2 for reaching remission at 6 months.
In logistic regression, the change at 3 months was significantly associated with reaching the target at 6 months.
Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.
Three months marks a critical time point that determines whether a rheumatoid arthritis patient will reach a treatment target at 6 months, according to results of a study published in Annals of the Rheumatic Diseases.
Dr. Daniel Aletaha of the Medical University of Vienna and his associates performed a pooled analysis of clinical data from RA trials in the last decade. They found that, regardless of the starting point, 6-month success rates were clearly related to disease activity state reached at 3 months, and not so much to the number of disease activity categories improved.
The results show that a response at 3 months can be used as a decision criterion in two clinical situations. Failure to achieve minor responses (for example, ACR 20, Simplified Disease Activity Index [SDAI] 50) at the 3-month mark had the potential to almost rule out successfully reaching the target at 6 months, the investigators wrote (Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2015-208324).
Conversely, achievement of major response definitions at 3 months (for example, ACR 70, SDAI 85%) can reliably predict achievement of a good state at 6 months.
“It is also obvious therefore that for many patients in the gray zone between these response levels, the prediction may be less solid, and may – to a greater extent – rest on the physician’s decision,” they wrote.
The findings were in line with updated treat-to-target (T2T) recommendations that suggest a goal of significant improvement at 3 months and attainment of the treatment target at 6 months, they added.
The study results showed that in order to be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI/Clinical Disease Activity Index needed to be observed at 3 months.
Patients who did not achieve the (minor) SDAI 50% response level had very low negative likelihood ratios of 0.28 for low disease activity and 0.07 for remission at 6 months. Patients who achieved the (major) SDAI 85% response had substantial positive likelihood ratios of 9.2 for reaching low disease activity and 6.2 for reaching remission at 6 months.
In logistic regression, the change at 3 months was significantly associated with reaching the target at 6 months.
Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.
Three months marks a critical time point that determines whether a rheumatoid arthritis patient will reach a treatment target at 6 months, according to results of a study published in Annals of the Rheumatic Diseases.
Dr. Daniel Aletaha of the Medical University of Vienna and his associates performed a pooled analysis of clinical data from RA trials in the last decade. They found that, regardless of the starting point, 6-month success rates were clearly related to disease activity state reached at 3 months, and not so much to the number of disease activity categories improved.
The results show that a response at 3 months can be used as a decision criterion in two clinical situations. Failure to achieve minor responses (for example, ACR 20, Simplified Disease Activity Index [SDAI] 50) at the 3-month mark had the potential to almost rule out successfully reaching the target at 6 months, the investigators wrote (Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2015-208324).
Conversely, achievement of major response definitions at 3 months (for example, ACR 70, SDAI 85%) can reliably predict achievement of a good state at 6 months.
“It is also obvious therefore that for many patients in the gray zone between these response levels, the prediction may be less solid, and may – to a greater extent – rest on the physician’s decision,” they wrote.
The findings were in line with updated treat-to-target (T2T) recommendations that suggest a goal of significant improvement at 3 months and attainment of the treatment target at 6 months, they added.
The study results showed that in order to be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI/Clinical Disease Activity Index needed to be observed at 3 months.
Patients who did not achieve the (minor) SDAI 50% response level had very low negative likelihood ratios of 0.28 for low disease activity and 0.07 for remission at 6 months. Patients who achieved the (major) SDAI 85% response had substantial positive likelihood ratios of 9.2 for reaching low disease activity and 6.2 for reaching remission at 6 months.
In logistic regression, the change at 3 months was significantly associated with reaching the target at 6 months.
Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:Failure to achieve minor responses at 3 months almost ruled out successfully reaching the target at 6 months.
Major finding: To be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI or Clinical Disease Activity Index needed to be observed at 3 months.
Data source: Pooled analysis of clinical data from RA trials in the last decade.
Disclosures: Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.
Shoulder strength is impaired in women with early-stage RA
In women, shoulder function is reduced early in the course of rheumatoid arthritis, based on a study published in Arthritis Research & Therapy.
At a mean of 20 months after diagnosis, women with rheumatoid arthritis (RA) had impaired shoulder muscle strength and shoulder-arm movement, and more shoulder pain, as compared to matched women without RA.
Lead author Dr. Annelie Bilberg of the University of Gothenburg in Sweden and her associates examined 103 women with rheumatoid arthritis and a reference group of 103 age-matched healthy women in a controlled cross-sectional study. Pain during shoulder and arm movements was assessed by the Borg symptom scale, and isometric muscle strength of the shoulder abductor muscles was assessed with an ISOBEX 3.0 dynamometer. Activity limitations were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Physical workload did not significantly differ between the patient and control groups.
At the time of the assessment, 53% of the patients and 20% of the controls reported shoulder symptoms. Shoulder muscle strength in the patient group was about 65% of that in the control group, and patients’ hand-grip force was approximately 55% of that in the controls. DASH questionnaire results averaged 25.7 in the patient group and 2.6 in the control group. All of the differences were statistically significant.
Shoulder function, emphasizing shoulder muscle strength, should be assessed at disease onset, the researchers advised. A prospective follow-up study of shoulder function in patients with new-onset RA would help to explain the natural progression of the disease.
Read the full article here: Arthritis Care and Research 2015. doi:10.1186/s13075-015-0777-0.
In women, shoulder function is reduced early in the course of rheumatoid arthritis, based on a study published in Arthritis Research & Therapy.
At a mean of 20 months after diagnosis, women with rheumatoid arthritis (RA) had impaired shoulder muscle strength and shoulder-arm movement, and more shoulder pain, as compared to matched women without RA.
Lead author Dr. Annelie Bilberg of the University of Gothenburg in Sweden and her associates examined 103 women with rheumatoid arthritis and a reference group of 103 age-matched healthy women in a controlled cross-sectional study. Pain during shoulder and arm movements was assessed by the Borg symptom scale, and isometric muscle strength of the shoulder abductor muscles was assessed with an ISOBEX 3.0 dynamometer. Activity limitations were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Physical workload did not significantly differ between the patient and control groups.
At the time of the assessment, 53% of the patients and 20% of the controls reported shoulder symptoms. Shoulder muscle strength in the patient group was about 65% of that in the control group, and patients’ hand-grip force was approximately 55% of that in the controls. DASH questionnaire results averaged 25.7 in the patient group and 2.6 in the control group. All of the differences were statistically significant.
Shoulder function, emphasizing shoulder muscle strength, should be assessed at disease onset, the researchers advised. A prospective follow-up study of shoulder function in patients with new-onset RA would help to explain the natural progression of the disease.
Read the full article here: Arthritis Care and Research 2015. doi:10.1186/s13075-015-0777-0.
In women, shoulder function is reduced early in the course of rheumatoid arthritis, based on a study published in Arthritis Research & Therapy.
At a mean of 20 months after diagnosis, women with rheumatoid arthritis (RA) had impaired shoulder muscle strength and shoulder-arm movement, and more shoulder pain, as compared to matched women without RA.
Lead author Dr. Annelie Bilberg of the University of Gothenburg in Sweden and her associates examined 103 women with rheumatoid arthritis and a reference group of 103 age-matched healthy women in a controlled cross-sectional study. Pain during shoulder and arm movements was assessed by the Borg symptom scale, and isometric muscle strength of the shoulder abductor muscles was assessed with an ISOBEX 3.0 dynamometer. Activity limitations were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Physical workload did not significantly differ between the patient and control groups.
At the time of the assessment, 53% of the patients and 20% of the controls reported shoulder symptoms. Shoulder muscle strength in the patient group was about 65% of that in the control group, and patients’ hand-grip force was approximately 55% of that in the controls. DASH questionnaire results averaged 25.7 in the patient group and 2.6 in the control group. All of the differences were statistically significant.
Shoulder function, emphasizing shoulder muscle strength, should be assessed at disease onset, the researchers advised. A prospective follow-up study of shoulder function in patients with new-onset RA would help to explain the natural progression of the disease.
Read the full article here: Arthritis Care and Research 2015. doi:10.1186/s13075-015-0777-0.
FROM ARTHRITIS RESEARCH & THERAPY
MBDA score can help to predict RA radiographic progression
Multibiomarker disease activity scores were significantly associated with joint damage after 1 year in rheumatoid arthritis patients taking nonbiologic disease-modifying antirheumatic drug therapy even after adjustment for several established risk factors for joint damage in an observational study.
Lead author Dr. Wanying Li of Crescendo Bioscience and associates determined multibiomarker disease activity (MBDA) scores during 271 visits in 163 patients with established rheumatoid arthritis who received nonbiologic disease-modifying antirheumatic drug therapy. The MBDA combines the serum concentrations of 12 biomarkers via a validated algorithm to quantify disease activity. The patients had a mean MBDA score of 43 (possible range 1-100), a mean age of 55 years, and two-thirds were female. Rheumatoid factor and anti-CCP each was positive in two-thirds of patients.
The investigators noted that radiographic progression – both joint space narrowing and joint erosion – was infrequent during the following year when MBDA scores were low, but the frequency and severity of radiographic progression increased as MBDA scores became higher. Progression was not observed for all patients with MBDA scores greater than 44 – the optimal score threshold for predicting progression – but the risk of progression continued to increase within the high MBDA range. The MBDA score remained significantly associated with subsequent joint damage after adjusting for 28-joint swollen joint count, 28-joint disease activity score using C-reactive protein (CRP), CRP, total Sharp van der Heijde score, and serologic status.
“These findings suggest that the MBDA score may be able to complement conventional tools for assessing RA patients during DMARD therapy and to help determine which patients need treatment intensification to prevent progressive joint damage,” the authors wrote.
Read the full article in Rheumatology (doi: 10.1093/rheumatology/kev341).
Multibiomarker disease activity scores were significantly associated with joint damage after 1 year in rheumatoid arthritis patients taking nonbiologic disease-modifying antirheumatic drug therapy even after adjustment for several established risk factors for joint damage in an observational study.
Lead author Dr. Wanying Li of Crescendo Bioscience and associates determined multibiomarker disease activity (MBDA) scores during 271 visits in 163 patients with established rheumatoid arthritis who received nonbiologic disease-modifying antirheumatic drug therapy. The MBDA combines the serum concentrations of 12 biomarkers via a validated algorithm to quantify disease activity. The patients had a mean MBDA score of 43 (possible range 1-100), a mean age of 55 years, and two-thirds were female. Rheumatoid factor and anti-CCP each was positive in two-thirds of patients.
The investigators noted that radiographic progression – both joint space narrowing and joint erosion – was infrequent during the following year when MBDA scores were low, but the frequency and severity of radiographic progression increased as MBDA scores became higher. Progression was not observed for all patients with MBDA scores greater than 44 – the optimal score threshold for predicting progression – but the risk of progression continued to increase within the high MBDA range. The MBDA score remained significantly associated with subsequent joint damage after adjusting for 28-joint swollen joint count, 28-joint disease activity score using C-reactive protein (CRP), CRP, total Sharp van der Heijde score, and serologic status.
“These findings suggest that the MBDA score may be able to complement conventional tools for assessing RA patients during DMARD therapy and to help determine which patients need treatment intensification to prevent progressive joint damage,” the authors wrote.
Read the full article in Rheumatology (doi: 10.1093/rheumatology/kev341).
Multibiomarker disease activity scores were significantly associated with joint damage after 1 year in rheumatoid arthritis patients taking nonbiologic disease-modifying antirheumatic drug therapy even after adjustment for several established risk factors for joint damage in an observational study.
Lead author Dr. Wanying Li of Crescendo Bioscience and associates determined multibiomarker disease activity (MBDA) scores during 271 visits in 163 patients with established rheumatoid arthritis who received nonbiologic disease-modifying antirheumatic drug therapy. The MBDA combines the serum concentrations of 12 biomarkers via a validated algorithm to quantify disease activity. The patients had a mean MBDA score of 43 (possible range 1-100), a mean age of 55 years, and two-thirds were female. Rheumatoid factor and anti-CCP each was positive in two-thirds of patients.
The investigators noted that radiographic progression – both joint space narrowing and joint erosion – was infrequent during the following year when MBDA scores were low, but the frequency and severity of radiographic progression increased as MBDA scores became higher. Progression was not observed for all patients with MBDA scores greater than 44 – the optimal score threshold for predicting progression – but the risk of progression continued to increase within the high MBDA range. The MBDA score remained significantly associated with subsequent joint damage after adjusting for 28-joint swollen joint count, 28-joint disease activity score using C-reactive protein (CRP), CRP, total Sharp van der Heijde score, and serologic status.
“These findings suggest that the MBDA score may be able to complement conventional tools for assessing RA patients during DMARD therapy and to help determine which patients need treatment intensification to prevent progressive joint damage,” the authors wrote.
Read the full article in Rheumatology (doi: 10.1093/rheumatology/kev341).
FROM RHEUMATOLOGY
Methotrexate ups risk of liver abnormalities, but not serious hepatic events
Methotrexate use more than doubled the risk of liver enzyme abnormalities but was not tied to serious hepatic outcomes among patients with rheumatic diseases, according to a meta-analysis of 32 randomized, controlled trials.
“Serious liver events were rare, with a suggestion of a trend towards fewer poor liver outcomes,” wrote Dr. Richard Conway of Galway (Ireland) University Hospitals. “The short duration of the included studies and the lack of liver biopsies are limitations, but the available data provide robust evidence for short-term safety” of methotrexate, wrote Dr. Conway and his associates.
Methotrexate is a first-line RA therapy with efficacy in several other inflammatory diseases, but concerns about toxicity have limited its use, the researchers noted. Clinicians have particularly debated its hepatic effects, in part because it can be “exceedingly difficult” to determine if liver disease is preexisting, methotrexate related, or caused by other medications or comorbidities, they said. To better assess the issue, they searched PubMed and the Cochrane Central Register of Controlled Trials for relevant double-blind, randomized, controlled trials published between 1990 and 2014. They found 32 such trials that included 13,177 patients with rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease (Semin Arthritis Rheum. 2015;45:156-62). Methotrexate use approximately doubled the risk of any adverse hepatic event (relative risk, 2.19; 95% confidence interval, 1.73-2.77) and of major and minor liver enzyme abnormalities (RR, 2.16; 95% CI, 1.67-2.79), but did not increase the risk of liver failure, cirrhosis, or liver-related mortality (RR, 0.12; 95% CI, 0.01-1.09), the investigators reported. “Clinical trials have inherent limitations, including short duration, selection bias, failure to collect information or reports that are not part of a prespecified protocol, and limited power to evaluate rare or unusual reports,” they cautioned. “While meta-analyses help overcome the last of these, the others raise some concern.”
But several other reports align with their results, the researchers noted. In an analysis of methotrexate studies lasting at least 2 years, about 10% of patients developed at least one minor liver enzyme abnormality, but less than 4% stopped methotrexate because of liver toxicity. Other controlled studies did not link methotrexate to severe fibrosis or cirrhosis – even after 4 years of treatment, they added. “It appears likely that serious liver-related complications due to methotrexate may take many years of treatment to manifest,” the investigators concluded.
The researchers reported no funding sources or conflicts of interest.
Methotrexate use more than doubled the risk of liver enzyme abnormalities but was not tied to serious hepatic outcomes among patients with rheumatic diseases, according to a meta-analysis of 32 randomized, controlled trials.
“Serious liver events were rare, with a suggestion of a trend towards fewer poor liver outcomes,” wrote Dr. Richard Conway of Galway (Ireland) University Hospitals. “The short duration of the included studies and the lack of liver biopsies are limitations, but the available data provide robust evidence for short-term safety” of methotrexate, wrote Dr. Conway and his associates.
Methotrexate is a first-line RA therapy with efficacy in several other inflammatory diseases, but concerns about toxicity have limited its use, the researchers noted. Clinicians have particularly debated its hepatic effects, in part because it can be “exceedingly difficult” to determine if liver disease is preexisting, methotrexate related, or caused by other medications or comorbidities, they said. To better assess the issue, they searched PubMed and the Cochrane Central Register of Controlled Trials for relevant double-blind, randomized, controlled trials published between 1990 and 2014. They found 32 such trials that included 13,177 patients with rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease (Semin Arthritis Rheum. 2015;45:156-62). Methotrexate use approximately doubled the risk of any adverse hepatic event (relative risk, 2.19; 95% confidence interval, 1.73-2.77) and of major and minor liver enzyme abnormalities (RR, 2.16; 95% CI, 1.67-2.79), but did not increase the risk of liver failure, cirrhosis, or liver-related mortality (RR, 0.12; 95% CI, 0.01-1.09), the investigators reported. “Clinical trials have inherent limitations, including short duration, selection bias, failure to collect information or reports that are not part of a prespecified protocol, and limited power to evaluate rare or unusual reports,” they cautioned. “While meta-analyses help overcome the last of these, the others raise some concern.”
But several other reports align with their results, the researchers noted. In an analysis of methotrexate studies lasting at least 2 years, about 10% of patients developed at least one minor liver enzyme abnormality, but less than 4% stopped methotrexate because of liver toxicity. Other controlled studies did not link methotrexate to severe fibrosis or cirrhosis – even after 4 years of treatment, they added. “It appears likely that serious liver-related complications due to methotrexate may take many years of treatment to manifest,” the investigators concluded.
The researchers reported no funding sources or conflicts of interest.
Methotrexate use more than doubled the risk of liver enzyme abnormalities but was not tied to serious hepatic outcomes among patients with rheumatic diseases, according to a meta-analysis of 32 randomized, controlled trials.
“Serious liver events were rare, with a suggestion of a trend towards fewer poor liver outcomes,” wrote Dr. Richard Conway of Galway (Ireland) University Hospitals. “The short duration of the included studies and the lack of liver biopsies are limitations, but the available data provide robust evidence for short-term safety” of methotrexate, wrote Dr. Conway and his associates.
Methotrexate is a first-line RA therapy with efficacy in several other inflammatory diseases, but concerns about toxicity have limited its use, the researchers noted. Clinicians have particularly debated its hepatic effects, in part because it can be “exceedingly difficult” to determine if liver disease is preexisting, methotrexate related, or caused by other medications or comorbidities, they said. To better assess the issue, they searched PubMed and the Cochrane Central Register of Controlled Trials for relevant double-blind, randomized, controlled trials published between 1990 and 2014. They found 32 such trials that included 13,177 patients with rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease (Semin Arthritis Rheum. 2015;45:156-62). Methotrexate use approximately doubled the risk of any adverse hepatic event (relative risk, 2.19; 95% confidence interval, 1.73-2.77) and of major and minor liver enzyme abnormalities (RR, 2.16; 95% CI, 1.67-2.79), but did not increase the risk of liver failure, cirrhosis, or liver-related mortality (RR, 0.12; 95% CI, 0.01-1.09), the investigators reported. “Clinical trials have inherent limitations, including short duration, selection bias, failure to collect information or reports that are not part of a prespecified protocol, and limited power to evaluate rare or unusual reports,” they cautioned. “While meta-analyses help overcome the last of these, the others raise some concern.”
But several other reports align with their results, the researchers noted. In an analysis of methotrexate studies lasting at least 2 years, about 10% of patients developed at least one minor liver enzyme abnormality, but less than 4% stopped methotrexate because of liver toxicity. Other controlled studies did not link methotrexate to severe fibrosis or cirrhosis – even after 4 years of treatment, they added. “It appears likely that serious liver-related complications due to methotrexate may take many years of treatment to manifest,” the investigators concluded.
The researchers reported no funding sources or conflicts of interest.
FROM SEMINARS IN ARTHRITIS AND RHEUMATISM
Key clinical point: Use of methotrexate increased the risk of hepatic enzyme abnormalities but not serious liver-related events among patients with inflammatory diseases.
Major finding: Methotrexate use approximately doubled the risk of any adverse liver event (RR, 2.19) but did not increase the risk of cirrhosis, liver failure, or liver-related death.
Data source: A meta-analysis of 32 randomized, controlled trials of methotrexate in rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel disease.
Disclosures: The investigators reported no funding sources or conflicts of interest.
Biomarker test couldn’t predict RA transformation from undifferentiated arthritis
Baseline assessment of patients with undifferentiated arthritis at an early disease stage with the multibiomarker disease activity score did not discriminate patients who continued to have undifferentiated disease at 2 years from those who met classification criteria for rheumatoid arthritis in a prospective cohort study.
Tender joint count based on 68 joints at baseline and female sex, but not the multibiomarker disease activity (MBDA) score, were significant predictors of developing rheumatoid arthritis (RA) in the study of 45 patients who had undifferentiated arthritis (UA) and 81 who had RA based on 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, Dr. Karen I. Maijer of the University of Amsterdam and her colleagues reported.
At baseline, all the patients had one or more swollen joints, had clinical symptoms for less than 1 year, and had never taken disease-modifying antirheumatic drugs or corticosteroids. Following evaluation and serum collection, the patients were treated according to EULAR guidelines. Of the 45 with UA, 29 continued to have UA at 2-year follow-up and 16 developed RA.
The results of the study indicated, however, that the baseline MBDA scores were higher in patients with an initial RA diagnosis than in those with UA, which is consistent with its validation in tracking disease activity in RA patients.
Read the full study in Annals of the Rheumatic Diseases (2015 Sept. 2 doi: 10.1136/annrheumdis-2015-207911).
Baseline assessment of patients with undifferentiated arthritis at an early disease stage with the multibiomarker disease activity score did not discriminate patients who continued to have undifferentiated disease at 2 years from those who met classification criteria for rheumatoid arthritis in a prospective cohort study.
Tender joint count based on 68 joints at baseline and female sex, but not the multibiomarker disease activity (MBDA) score, were significant predictors of developing rheumatoid arthritis (RA) in the study of 45 patients who had undifferentiated arthritis (UA) and 81 who had RA based on 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, Dr. Karen I. Maijer of the University of Amsterdam and her colleagues reported.
At baseline, all the patients had one or more swollen joints, had clinical symptoms for less than 1 year, and had never taken disease-modifying antirheumatic drugs or corticosteroids. Following evaluation and serum collection, the patients were treated according to EULAR guidelines. Of the 45 with UA, 29 continued to have UA at 2-year follow-up and 16 developed RA.
The results of the study indicated, however, that the baseline MBDA scores were higher in patients with an initial RA diagnosis than in those with UA, which is consistent with its validation in tracking disease activity in RA patients.
Read the full study in Annals of the Rheumatic Diseases (2015 Sept. 2 doi: 10.1136/annrheumdis-2015-207911).
Baseline assessment of patients with undifferentiated arthritis at an early disease stage with the multibiomarker disease activity score did not discriminate patients who continued to have undifferentiated disease at 2 years from those who met classification criteria for rheumatoid arthritis in a prospective cohort study.
Tender joint count based on 68 joints at baseline and female sex, but not the multibiomarker disease activity (MBDA) score, were significant predictors of developing rheumatoid arthritis (RA) in the study of 45 patients who had undifferentiated arthritis (UA) and 81 who had RA based on 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, Dr. Karen I. Maijer of the University of Amsterdam and her colleagues reported.
At baseline, all the patients had one or more swollen joints, had clinical symptoms for less than 1 year, and had never taken disease-modifying antirheumatic drugs or corticosteroids. Following evaluation and serum collection, the patients were treated according to EULAR guidelines. Of the 45 with UA, 29 continued to have UA at 2-year follow-up and 16 developed RA.
The results of the study indicated, however, that the baseline MBDA scores were higher in patients with an initial RA diagnosis than in those with UA, which is consistent with its validation in tracking disease activity in RA patients.
Read the full study in Annals of the Rheumatic Diseases (2015 Sept. 2 doi: 10.1136/annrheumdis-2015-207911).
Infliximab biosimilar SB2 shows efficacy, safety similar to Remicade for RA
The investigational infliximab biosimilar drug SB2 provided efficacy and safety equivalent to the originator drug Remicade in patients with moderate to severe rheumatoid arthritis in a phase III study that studied the drugs in combination with methotrexate.
Treatment with SB2, which is under development by Samsung Bioepis, met the prespecified definition of equivalence to Remicade on the primary efficacy endpoint of American College of Rheumatology 20 response rate at 30 weeks by staying within a margin of −15% and +15% on the 95% confidence interval of the ACR20 rate difference (64.1% for SB2 vs. 66.0%; 95% CI, –10.26% to 6.51%). Other efficacy outcomes also showed similarity between SB2 and Remicade, including disease activity score based on 28 joints, simplified disease activity index, clinical disease activity index, and European League Against Rheumatism (EULAR) response, Dr. Jung-Yoon Choe of Daegu Catholic University Medical Center, South Korea, and colleagues reported.
Treatment-emergent adverse events occurred in 58% of patients in both groups, including 9% with at least one serious event in each group. Latent tuberculosis (TB) infections occurred in 6%-7% of patients, and none developed active TB after prophylaxis. Serious infection or active TB occurred in 3.1% of SB2 and 2.0% of Remicade patients. Only one patient in each group developed active TB, and neither had latent TB at screening.
The trial involved 584 patients who were randomized double blind to 3 mg/kg IV infusion of either drug at week 0, week 2, week 6, week 14, week 22, and week 30. The patients took 10-25 mg/week oral or parenteral methotrexate along with 5-10 mg/week folic acid. The investigators allowed nonsteroidal anti-inflammatory drugs and corticosteroids at doses equivalent to 10 mg or less prednisolone if they had been taken on a stable dose for 4 weeks before randomization. Each patient had to have had RA for at least 6 months with least six tender joints and six swollen joints, as well as an erythrocyte sedimentation rate of 28 mm/h or greater or a C-reactive protein level of 1.0 mg/dL or higher. Patients had to take methotrexate for at least 6 months with a stable dose for the 4 weeks before randomization.
Read the full study in Annals of the Rheumatic Diseases (2015 Aug. 28 doi: 10.1136/annrheumdis-2015-207764).
The investigational infliximab biosimilar drug SB2 provided efficacy and safety equivalent to the originator drug Remicade in patients with moderate to severe rheumatoid arthritis in a phase III study that studied the drugs in combination with methotrexate.
Treatment with SB2, which is under development by Samsung Bioepis, met the prespecified definition of equivalence to Remicade on the primary efficacy endpoint of American College of Rheumatology 20 response rate at 30 weeks by staying within a margin of −15% and +15% on the 95% confidence interval of the ACR20 rate difference (64.1% for SB2 vs. 66.0%; 95% CI, –10.26% to 6.51%). Other efficacy outcomes also showed similarity between SB2 and Remicade, including disease activity score based on 28 joints, simplified disease activity index, clinical disease activity index, and European League Against Rheumatism (EULAR) response, Dr. Jung-Yoon Choe of Daegu Catholic University Medical Center, South Korea, and colleagues reported.
Treatment-emergent adverse events occurred in 58% of patients in both groups, including 9% with at least one serious event in each group. Latent tuberculosis (TB) infections occurred in 6%-7% of patients, and none developed active TB after prophylaxis. Serious infection or active TB occurred in 3.1% of SB2 and 2.0% of Remicade patients. Only one patient in each group developed active TB, and neither had latent TB at screening.
The trial involved 584 patients who were randomized double blind to 3 mg/kg IV infusion of either drug at week 0, week 2, week 6, week 14, week 22, and week 30. The patients took 10-25 mg/week oral or parenteral methotrexate along with 5-10 mg/week folic acid. The investigators allowed nonsteroidal anti-inflammatory drugs and corticosteroids at doses equivalent to 10 mg or less prednisolone if they had been taken on a stable dose for 4 weeks before randomization. Each patient had to have had RA for at least 6 months with least six tender joints and six swollen joints, as well as an erythrocyte sedimentation rate of 28 mm/h or greater or a C-reactive protein level of 1.0 mg/dL or higher. Patients had to take methotrexate for at least 6 months with a stable dose for the 4 weeks before randomization.
Read the full study in Annals of the Rheumatic Diseases (2015 Aug. 28 doi: 10.1136/annrheumdis-2015-207764).
The investigational infliximab biosimilar drug SB2 provided efficacy and safety equivalent to the originator drug Remicade in patients with moderate to severe rheumatoid arthritis in a phase III study that studied the drugs in combination with methotrexate.
Treatment with SB2, which is under development by Samsung Bioepis, met the prespecified definition of equivalence to Remicade on the primary efficacy endpoint of American College of Rheumatology 20 response rate at 30 weeks by staying within a margin of −15% and +15% on the 95% confidence interval of the ACR20 rate difference (64.1% for SB2 vs. 66.0%; 95% CI, –10.26% to 6.51%). Other efficacy outcomes also showed similarity between SB2 and Remicade, including disease activity score based on 28 joints, simplified disease activity index, clinical disease activity index, and European League Against Rheumatism (EULAR) response, Dr. Jung-Yoon Choe of Daegu Catholic University Medical Center, South Korea, and colleagues reported.
Treatment-emergent adverse events occurred in 58% of patients in both groups, including 9% with at least one serious event in each group. Latent tuberculosis (TB) infections occurred in 6%-7% of patients, and none developed active TB after prophylaxis. Serious infection or active TB occurred in 3.1% of SB2 and 2.0% of Remicade patients. Only one patient in each group developed active TB, and neither had latent TB at screening.
The trial involved 584 patients who were randomized double blind to 3 mg/kg IV infusion of either drug at week 0, week 2, week 6, week 14, week 22, and week 30. The patients took 10-25 mg/week oral or parenteral methotrexate along with 5-10 mg/week folic acid. The investigators allowed nonsteroidal anti-inflammatory drugs and corticosteroids at doses equivalent to 10 mg or less prednisolone if they had been taken on a stable dose for 4 weeks before randomization. Each patient had to have had RA for at least 6 months with least six tender joints and six swollen joints, as well as an erythrocyte sedimentation rate of 28 mm/h or greater or a C-reactive protein level of 1.0 mg/dL or higher. Patients had to take methotrexate for at least 6 months with a stable dose for the 4 weeks before randomization.
Read the full study in Annals of the Rheumatic Diseases (2015 Aug. 28 doi: 10.1136/annrheumdis-2015-207764).
VIDEO: Use fiduciary duty to set pain medication boundaries
ORLANDO – Physicians should use the concept of fiduciary duty to set appropriate boundaries with patients taking pain medications, explained Dr. Louis Kuritzky.
Often, patients want treatments that are not in their best interests, noted Dr. Kuritzky of the department of community health and family medicine at the University of Florida, Gainesville.
In an interview at a meeting held by the American Pain Society and Global Academy for Medical Education, Dr. Kuritzky outlined how physicians can take a fiduciary duty approach to set boundaries with patients in a dispassionate manner.
Global Academy and this news organization are owned by the same company. Dr. Kuritzky reported a financial relationship with Lilly.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ORLANDO – Physicians should use the concept of fiduciary duty to set appropriate boundaries with patients taking pain medications, explained Dr. Louis Kuritzky.
Often, patients want treatments that are not in their best interests, noted Dr. Kuritzky of the department of community health and family medicine at the University of Florida, Gainesville.
In an interview at a meeting held by the American Pain Society and Global Academy for Medical Education, Dr. Kuritzky outlined how physicians can take a fiduciary duty approach to set boundaries with patients in a dispassionate manner.
Global Academy and this news organization are owned by the same company. Dr. Kuritzky reported a financial relationship with Lilly.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ORLANDO – Physicians should use the concept of fiduciary duty to set appropriate boundaries with patients taking pain medications, explained Dr. Louis Kuritzky.
Often, patients want treatments that are not in their best interests, noted Dr. Kuritzky of the department of community health and family medicine at the University of Florida, Gainesville.
In an interview at a meeting held by the American Pain Society and Global Academy for Medical Education, Dr. Kuritzky outlined how physicians can take a fiduciary duty approach to set boundaries with patients in a dispassionate manner.
Global Academy and this news organization are owned by the same company. Dr. Kuritzky reported a financial relationship with Lilly.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
EXPERT ANALYSIS FROM PAIN CARE FOR PRIMARY CARE
ESC: Celecoxib safety study may soothe cardio concerns
LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.
Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.
In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.
The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.
“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.
The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.
More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.
General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.
Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).
There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).
Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.
The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).
“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”
Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.
The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.
The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.
LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.
Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.
In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.
The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.
“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.
The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.
More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.
General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.
Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).
There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).
Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.
The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).
“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”
Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.
The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.
The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.
LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.
Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.
In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.
The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.
“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.
The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.
More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.
General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.
Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).
There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).
Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.
The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).
“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”
Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.
The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.
The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.
AT THE ESC CONGRESS 2015
Key clinical point: Celecoxib and nonselective NSAIDs were “acceptably safe” in a population without confirmed cardiovascular disease.
Major finding: The hazard ratio for the primary composite cardiovascular endpoint with celecoxib use was 1.12 (95% confidence interval, 0.81-1.55; P = .5), compared with NSAIDs.
Data source: The Standard Care Versus Celecoxib Outcome Trial (SCOT) of more than 7,200 elderly patients with osteoarthritis or rheumatoid arthritis and no confirmed cardiovascular disease.
Disclosures: The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.
