Rheumatoid Arthritis

Patients with rheumatoid arthritis had low rates of screening for primary hyperlipidemia, but patients who visited both a rheumatologist and a nonrheumatology clinician for follow-up were more likely to be screened, according to research published in Arthritis Care & Research.

American Heart Association

Iris Navarro-Millán, MD, MSPH, from Cornell University, New York, and her colleagues performed a retrospective study of roughly 244,000 participants with private insurance, Medicare, or Medicaid who had rheumatoid arthritis (13,000 patients), diabetes (63,000), both rheumatoid arthritis (RA) and diabetes (1,000), and neither RA nor diabetes (168,000) during 2006-2010. Patients were between the ages of 41 years and 85 years. There were similar rates of hypertension among the RA patients (40%) and patients with neither RA nor diabetes (39%), as well as among the diabetes patients (79%) and the both patients with both RA and diabetes (70%).

The researchers found 37% of RA patients, 60% of diabetes patients, 55% of patients with both RA and diabetes, and 41% of patients with neither RA nor diabetes received primary lipid screening over 2 years’ follow-up. For RA-only patients, 22% saw a rheumatologist only, while 56% saw both a rheumatologist and then a nonrheumatology clinician at 2-years’ follow-up. Patients who visited a rheumatologist and a nonrheumatology clinician for follow-up were 55% more likely to receive primary lipid screening, and RA patients who visited a nonrheumatology clinician only were 22% more likely to receive screening than RA patients who saw only a rheumatologist.

Dr. Navarro-Millán and her colleagues said European RA patients may be more likely to receive screening for hyperlipidemia because their health care systems follow European League Against Rheumatism (EULAR) recommendations for management of cardiovascular disease (CVD) risk, while many rheumatologists based in the United States are “still reluctant to take responsibility to assess and mitigate (if needed) CVD risk for patients with RA.”

“Measures to achieve this goal must be implemented and may include defining specific roles for rheumatologists, nonrheumatology practitioners, and patients to determine who should be responsible for hyperlipidemia screening and treatment for patients with RA,” Dr. Navarro-Millán and her colleagues wrote.

Limitations to the study include lack of information on uninsured patients, lack of some clinical and demographic data, and potential misclassification of some clinicians who may have provided rheumatology-specific care but may have been in primary care settings.

This study is funded by grants and contracts from the National Institutes of Health and the Department of Health and Human Services. The authors report no relevant financial disclosures.

SOURCE: Navarro-Millán I et al. Arthritis Care Res. 2018. doi: 10.1002/acr.23810.

Patients with rheumatoid arthritis had low rates of screening for primary hyperlipidemia, but patients who visited both a rheumatologist and a nonrheumatology clinician for follow-up were more likely to be screened, according to research published in Arthritis Care & Research.

American Heart Association

Iris Navarro-Millán, MD, MSPH, from Cornell University, New York, and her colleagues performed a retrospective study of roughly 244,000 participants with private insurance, Medicare, or Medicaid who had rheumatoid arthritis (13,000 patients), diabetes (63,000), both rheumatoid arthritis (RA) and diabetes (1,000), and neither RA nor diabetes (168,000) during 2006-2010. Patients were between the ages of 41 years and 85 years. There were similar rates of hypertension among the RA patients (40%) and patients with neither RA nor diabetes (39%), as well as among the diabetes patients (79%) and the both patients with both RA and diabetes (70%).

The researchers found 37% of RA patients, 60% of diabetes patients, 55% of patients with both RA and diabetes, and 41% of patients with neither RA nor diabetes received primary lipid screening over 2 years’ follow-up. For RA-only patients, 22% saw a rheumatologist only, while 56% saw both a rheumatologist and then a nonrheumatology clinician at 2-years’ follow-up. Patients who visited a rheumatologist and a nonrheumatology clinician for follow-up were 55% more likely to receive primary lipid screening, and RA patients who visited a nonrheumatology clinician only were 22% more likely to receive screening than RA patients who saw only a rheumatologist.

Dr. Navarro-Millán and her colleagues said European RA patients may be more likely to receive screening for hyperlipidemia because their health care systems follow European League Against Rheumatism (EULAR) recommendations for management of cardiovascular disease (CVD) risk, while many rheumatologists based in the United States are “still reluctant to take responsibility to assess and mitigate (if needed) CVD risk for patients with RA.”

“Measures to achieve this goal must be implemented and may include defining specific roles for rheumatologists, nonrheumatology practitioners, and patients to determine who should be responsible for hyperlipidemia screening and treatment for patients with RA,” Dr. Navarro-Millán and her colleagues wrote.

Limitations to the study include lack of information on uninsured patients, lack of some clinical and demographic data, and potential misclassification of some clinicians who may have provided rheumatology-specific care but may have been in primary care settings.

This study is funded by grants and contracts from the National Institutes of Health and the Department of Health and Human Services. The authors report no relevant financial disclosures.

SOURCE: Navarro-Millán I et al. Arthritis Care Res. 2018. doi: 10.1002/acr.23810.

Patients with rheumatoid arthritis had low rates of screening for primary hyperlipidemia, but patients who visited both a rheumatologist and a nonrheumatology clinician for follow-up were more likely to be screened, according to research published in Arthritis Care & Research.

American Heart Association

Iris Navarro-Millán, MD, MSPH, from Cornell University, New York, and her colleagues performed a retrospective study of roughly 244,000 participants with private insurance, Medicare, or Medicaid who had rheumatoid arthritis (13,000 patients), diabetes (63,000), both rheumatoid arthritis (RA) and diabetes (1,000), and neither RA nor diabetes (168,000) during 2006-2010. Patients were between the ages of 41 years and 85 years. There were similar rates of hypertension among the RA patients (40%) and patients with neither RA nor diabetes (39%), as well as among the diabetes patients (79%) and the both patients with both RA and diabetes (70%).

The researchers found 37% of RA patients, 60% of diabetes patients, 55% of patients with both RA and diabetes, and 41% of patients with neither RA nor diabetes received primary lipid screening over 2 years’ follow-up. For RA-only patients, 22% saw a rheumatologist only, while 56% saw both a rheumatologist and then a nonrheumatology clinician at 2-years’ follow-up. Patients who visited a rheumatologist and a nonrheumatology clinician for follow-up were 55% more likely to receive primary lipid screening, and RA patients who visited a nonrheumatology clinician only were 22% more likely to receive screening than RA patients who saw only a rheumatologist.

Dr. Navarro-Millán and her colleagues said European RA patients may be more likely to receive screening for hyperlipidemia because their health care systems follow European League Against Rheumatism (EULAR) recommendations for management of cardiovascular disease (CVD) risk, while many rheumatologists based in the United States are “still reluctant to take responsibility to assess and mitigate (if needed) CVD risk for patients with RA.”

“Measures to achieve this goal must be implemented and may include defining specific roles for rheumatologists, nonrheumatology practitioners, and patients to determine who should be responsible for hyperlipidemia screening and treatment for patients with RA,” Dr. Navarro-Millán and her colleagues wrote.

Limitations to the study include lack of information on uninsured patients, lack of some clinical and demographic data, and potential misclassification of some clinicians who may have provided rheumatology-specific care but may have been in primary care settings.

This study is funded by grants and contracts from the National Institutes of Health and the Department of Health and Human Services. The authors report no relevant financial disclosures.

SOURCE: Navarro-Millán I et al. Arthritis Care Res. 2018. doi: 10.1002/acr.23810.

CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.

Mitchel L. Zoler/MDedge News

The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.

Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.

In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.

Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.

The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.

The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.

Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.

mzoler@mdedge.com

SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.

CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.

Mitchel L. Zoler/MDedge News

The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.

Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.

In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.

Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.

The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.

The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.

Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.

mzoler@mdedge.com

SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.

CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.

Mitchel L. Zoler/MDedge News

The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.

Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.

In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.

Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.

The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.

The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.

Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.

mzoler@mdedge.com

SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.

CHICAGO – The American College of Rheumatology is continuing to work on its physician-focused advanced alternative payment model (APM) pathway for RA, with hopes to send the fully developed model to the Physician-Focused Payment Model Technical Advisory Committee once financial data gathering and analysis is complete, followed by pilot testing once it is accepted by the Centers for Medicare & Medicaid Services, speakers said at the annual meeting of the ACR.

The “RA Care Team” APM is meant to be versatile and work across various practice settings, from rural Alaska and the Southwest to urban Chicago and Boston, and would consist of a rheumatologist or a nurse practitioner or physician assistant working with a rheumatologist in some areas, while in others a patient would be managed by a primary care physician who has a formal arrangement with a rheumatologist to provide early treatment of RA. Participation in the model would use a standard treatment approach pathway that follows ACR treatment guidelines and saves money by reducing the variability in initiation of expensive medications and would be versatile enough to allow for unique patients by requiring only 75% adherence to the pathway across a practice’s patients, said Kwas Huston, MD, cochair of the ACR’s APM work group and a rheumatologist with Kansas City (Mo.) Physician Partners.

The model covers four phases of care, including diagnosis and treatment planning for patients with potential RA, support for primary care practices in evaluating joint symptoms, the initial treatment of patients with RA, and the continued care of RA. For instance, a rheumatologist could receive payment for an e-consult with a primary care provider to determine if a patient has symptoms requiring an evaluation for RA. A rheumatologist could also receive a one-time payment for treatment and planning services when a diagnosis of RA cannot be established in a patient suspected of having RA, whereas the rheumatologist or a primary care provider with rheumatology support would receive monthly payments for 6 months for the initial treatment of an RA patient and then thereafter would receive monthly payments for continued care of RA. The payments would not be dependent on the number of visits or face-to-face time, would be stratified based on patient characteristics, and would include some lab testing and imaging.

Currently, the RA APM work group is analyzing financial data gathered from two large rheumatology practices for specific CPT codes matched to specific patients based on their clinical characteristics “to get a sense of how much revenue is coming in right now for practices taking care of patients with, let’s say, moderate disease activity and two comorbidities or low disease activity and no comorbidities,” Dr. Huston said. The work group is also surveying practices to estimate additional costs required to participate in the APM and thereby develop a financial model to adequately pay for APM services. They additionally plan to develop a tool kit that is designed to help individual practices determine the economic impact that the APM would have.

Notably, the cost of medications is not included in the APM. “That would be too much of a risk for small practices to take on,” Dr. Huston said.

“This model is a work in progress. We still have a lot of additional work to validate the data,” he added.

Providers who wish to participate in an advanced APM in 2019 need to have at least 25% of their Medicare Part B payments or have at least 20% of Medicare patients in their practice come through the APM in order to avoid having to submit data to comply with the performance criteria requirements of the Merit-Based Incentive Payment System, said Angus Worthing, MD, chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area.

“The ACR has advocated to reduce these thresholds over the years, but unfortunately that has not happened yet,” Dr. Worthing said.

jevans@mdedge.com

CHICAGO – The American College of Rheumatology is continuing to work on its physician-focused advanced alternative payment model (APM) pathway for RA, with hopes to send the fully developed model to the Physician-Focused Payment Model Technical Advisory Committee once financial data gathering and analysis is complete, followed by pilot testing once it is accepted by the Centers for Medicare & Medicaid Services, speakers said at the annual meeting of the ACR.

The “RA Care Team” APM is meant to be versatile and work across various practice settings, from rural Alaska and the Southwest to urban Chicago and Boston, and would consist of a rheumatologist or a nurse practitioner or physician assistant working with a rheumatologist in some areas, while in others a patient would be managed by a primary care physician who has a formal arrangement with a rheumatologist to provide early treatment of RA. Participation in the model would use a standard treatment approach pathway that follows ACR treatment guidelines and saves money by reducing the variability in initiation of expensive medications and would be versatile enough to allow for unique patients by requiring only 75% adherence to the pathway across a practice’s patients, said Kwas Huston, MD, cochair of the ACR’s APM work group and a rheumatologist with Kansas City (Mo.) Physician Partners.

The model covers four phases of care, including diagnosis and treatment planning for patients with potential RA, support for primary care practices in evaluating joint symptoms, the initial treatment of patients with RA, and the continued care of RA. For instance, a rheumatologist could receive payment for an e-consult with a primary care provider to determine if a patient has symptoms requiring an evaluation for RA. A rheumatologist could also receive a one-time payment for treatment and planning services when a diagnosis of RA cannot be established in a patient suspected of having RA, whereas the rheumatologist or a primary care provider with rheumatology support would receive monthly payments for 6 months for the initial treatment of an RA patient and then thereafter would receive monthly payments for continued care of RA. The payments would not be dependent on the number of visits or face-to-face time, would be stratified based on patient characteristics, and would include some lab testing and imaging.

Currently, the RA APM work group is analyzing financial data gathered from two large rheumatology practices for specific CPT codes matched to specific patients based on their clinical characteristics “to get a sense of how much revenue is coming in right now for practices taking care of patients with, let’s say, moderate disease activity and two comorbidities or low disease activity and no comorbidities,” Dr. Huston said. The work group is also surveying practices to estimate additional costs required to participate in the APM and thereby develop a financial model to adequately pay for APM services. They additionally plan to develop a tool kit that is designed to help individual practices determine the economic impact that the APM would have.

Notably, the cost of medications is not included in the APM. “That would be too much of a risk for small practices to take on,” Dr. Huston said.

“This model is a work in progress. We still have a lot of additional work to validate the data,” he added.

Providers who wish to participate in an advanced APM in 2019 need to have at least 25% of their Medicare Part B payments or have at least 20% of Medicare patients in their practice come through the APM in order to avoid having to submit data to comply with the performance criteria requirements of the Merit-Based Incentive Payment System, said Angus Worthing, MD, chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area.

“The ACR has advocated to reduce these thresholds over the years, but unfortunately that has not happened yet,” Dr. Worthing said.

jevans@mdedge.com

CHICAGO – The American College of Rheumatology is continuing to work on its physician-focused advanced alternative payment model (APM) pathway for RA, with hopes to send the fully developed model to the Physician-Focused Payment Model Technical Advisory Committee once financial data gathering and analysis is complete, followed by pilot testing once it is accepted by the Centers for Medicare & Medicaid Services, speakers said at the annual meeting of the ACR.

The “RA Care Team” APM is meant to be versatile and work across various practice settings, from rural Alaska and the Southwest to urban Chicago and Boston, and would consist of a rheumatologist or a nurse practitioner or physician assistant working with a rheumatologist in some areas, while in others a patient would be managed by a primary care physician who has a formal arrangement with a rheumatologist to provide early treatment of RA. Participation in the model would use a standard treatment approach pathway that follows ACR treatment guidelines and saves money by reducing the variability in initiation of expensive medications and would be versatile enough to allow for unique patients by requiring only 75% adherence to the pathway across a practice’s patients, said Kwas Huston, MD, cochair of the ACR’s APM work group and a rheumatologist with Kansas City (Mo.) Physician Partners.

The model covers four phases of care, including diagnosis and treatment planning for patients with potential RA, support for primary care practices in evaluating joint symptoms, the initial treatment of patients with RA, and the continued care of RA. For instance, a rheumatologist could receive payment for an e-consult with a primary care provider to determine if a patient has symptoms requiring an evaluation for RA. A rheumatologist could also receive a one-time payment for treatment and planning services when a diagnosis of RA cannot be established in a patient suspected of having RA, whereas the rheumatologist or a primary care provider with rheumatology support would receive monthly payments for 6 months for the initial treatment of an RA patient and then thereafter would receive monthly payments for continued care of RA. The payments would not be dependent on the number of visits or face-to-face time, would be stratified based on patient characteristics, and would include some lab testing and imaging.

Currently, the RA APM work group is analyzing financial data gathered from two large rheumatology practices for specific CPT codes matched to specific patients based on their clinical characteristics “to get a sense of how much revenue is coming in right now for practices taking care of patients with, let’s say, moderate disease activity and two comorbidities or low disease activity and no comorbidities,” Dr. Huston said. The work group is also surveying practices to estimate additional costs required to participate in the APM and thereby develop a financial model to adequately pay for APM services. They additionally plan to develop a tool kit that is designed to help individual practices determine the economic impact that the APM would have.

Notably, the cost of medications is not included in the APM. “That would be too much of a risk for small practices to take on,” Dr. Huston said.

“This model is a work in progress. We still have a lot of additional work to validate the data,” he added.

Providers who wish to participate in an advanced APM in 2019 need to have at least 25% of their Medicare Part B payments or have at least 20% of Medicare patients in their practice come through the APM in order to avoid having to submit data to comply with the performance criteria requirements of the Merit-Based Incentive Payment System, said Angus Worthing, MD, chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area.

“The ACR has advocated to reduce these thresholds over the years, but unfortunately that has not happened yet,” Dr. Worthing said.

jevans@mdedge.com

CHICAGO – The commercially available multibiomarker disease activity score assay and power Doppler ultrasound at baseline in rheumatoid arthritis patients treated with tofacitinib predicted 12-week responses on some clinical, imaging, and biomarker endpoints, according to findings from an investigator-initiated, open-label study.

The blood test–based multibiomarker disease activity (MBDA) score, which is calculated using measurements of 12 inflammatory biomarkers to score RA disease activity on a 0-100 point scale (Vectra DA, Myriad Autoimmune), also appears to track RA patients’ responses to rituximab, according to a post-hoc analysis of three cohort studies.

The findings of both studies were presented in posters at the annual meeting of the American College of Rheumatology. They are the first studies to evaluate early musculoskeletal ultrasound (MSUS) and MBDA score changes as predictors of response to tofacitinib in patients with RA, and the first to assess the ability of the MBDA score to track response to rituximab treatment. They provide valuable information that can help guide patient treatment and thereby improve outcomes, Elena Hitraya, MD, PhD, chief medical officer for Crescendo Bioscience/Myriad Autoimmune, San Francisco, said in an interview.

In the tofacitinib study, 25 RA patients with a mean age of 52 years, mean disease duration of 10.4 years, baseline Disease Activity Score 28-joint count (DAS28) greater than 3.2, and power Doppler ultrasound (PDUS) scores greater than 10 were treated with the approved oral tofacitinib dose of 5 mg twice daily. Assessments at baseline, 2 weeks, and 12 weeks included MSUS to score 34 joints for PDUS and gray scale ultrasound (GSUS), MBDA score, clinical disease activity index (CDAI), and DAS28, according to Amir Razmjou, MD, of the University of California, Los Angeles, and his colleagues.

Statistically significant improvement was seen on all measures over the 12-week study period (all at P less than .0001). For example, from baseline to 12 weeks the PDUS score improved from 28.6 to 12.2, GSUS score improved from 48.4 to 37.9, MBDA score improved from 50.6 to 39.6, CDAI score improved from 39.9 to 21.6, and DAS28–erythrocyte sedimentation rate (DAS28-ESR) score improved from 6.3 to 4.6, they said, noting further that baseline PDUS and MBDA scores significantly predicted CDAI and DAS28 responses at 12 weeks (P less than .01).

In the rituximab study, the MBDA score tracked disease activity in 57 RA patients from three different cohorts with a mean age of 57 years and mean disease duration of 11.5 years. Changes in the MBDA score reflected the degree of treatment response, Nadia M.T. Roodenrijs of University Medical Center Utrecht (the Netherlands) and her colleagues reported.

All patients were treated with 1,000 mg rituximab and 100 mg methylprednisolone on days 1 and 15, and MBDA score was assessed at baseline and 6 months.

MBDA scores correlated significantly with change from baseline to 6 months in DAS28-ESR (r = 0.60), DAS28–high-sensitivity C-reactive protein, (DAS28-hsCRP; r = 0.48), ESR (r = 0.48), and hsCRP (r = 0.71), and with European League Against Rheumatism (EULAR) good or moderate response at 6 months based on DAS28-ESR (adjusted odds ratio, 0.91).

Extensive work has been done to validate the MBDA score for assessing disease activity, and it has been shown to perform well for predicting response to a variety of disease-modifying antirheumatic drugs and biologic agents, Dr. Hitraya explained.

Additionally, multiple studies have demonstrated that the MBDA score defines risk categories for radiographic progression and performs better than traditional measures of disease activity for identifying those at increased risk of radiographic progression, which can help physicians mitigate associated risks through increased surveillance and therapeutic choices, she said.

“Having data for these specific molecules [tofacitinib and rituximab] is very important for rheumatologists,” Dr. Hitraya said.

The tofacitinib study was supported by Pfizer. Dr. Razmjou and Dr. Roodenrijs each reported having no disclosures.

sworcester@mdedge.com

SOURCE: Razmjou A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 582; Roodenrijs N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1500.

CHICAGO – The commercially available multibiomarker disease activity score assay and power Doppler ultrasound at baseline in rheumatoid arthritis patients treated with tofacitinib predicted 12-week responses on some clinical, imaging, and biomarker endpoints, according to findings from an investigator-initiated, open-label study.

The blood test–based multibiomarker disease activity (MBDA) score, which is calculated using measurements of 12 inflammatory biomarkers to score RA disease activity on a 0-100 point scale (Vectra DA, Myriad Autoimmune), also appears to track RA patients’ responses to rituximab, according to a post-hoc analysis of three cohort studies.

The findings of both studies were presented in posters at the annual meeting of the American College of Rheumatology. They are the first studies to evaluate early musculoskeletal ultrasound (MSUS) and MBDA score changes as predictors of response to tofacitinib in patients with RA, and the first to assess the ability of the MBDA score to track response to rituximab treatment. They provide valuable information that can help guide patient treatment and thereby improve outcomes, Elena Hitraya, MD, PhD, chief medical officer for Crescendo Bioscience/Myriad Autoimmune, San Francisco, said in an interview.

In the tofacitinib study, 25 RA patients with a mean age of 52 years, mean disease duration of 10.4 years, baseline Disease Activity Score 28-joint count (DAS28) greater than 3.2, and power Doppler ultrasound (PDUS) scores greater than 10 were treated with the approved oral tofacitinib dose of 5 mg twice daily. Assessments at baseline, 2 weeks, and 12 weeks included MSUS to score 34 joints for PDUS and gray scale ultrasound (GSUS), MBDA score, clinical disease activity index (CDAI), and DAS28, according to Amir Razmjou, MD, of the University of California, Los Angeles, and his colleagues.

Statistically significant improvement was seen on all measures over the 12-week study period (all at P less than .0001). For example, from baseline to 12 weeks the PDUS score improved from 28.6 to 12.2, GSUS score improved from 48.4 to 37.9, MBDA score improved from 50.6 to 39.6, CDAI score improved from 39.9 to 21.6, and DAS28–erythrocyte sedimentation rate (DAS28-ESR) score improved from 6.3 to 4.6, they said, noting further that baseline PDUS and MBDA scores significantly predicted CDAI and DAS28 responses at 12 weeks (P less than .01).

In the rituximab study, the MBDA score tracked disease activity in 57 RA patients from three different cohorts with a mean age of 57 years and mean disease duration of 11.5 years. Changes in the MBDA score reflected the degree of treatment response, Nadia M.T. Roodenrijs of University Medical Center Utrecht (the Netherlands) and her colleagues reported.

All patients were treated with 1,000 mg rituximab and 100 mg methylprednisolone on days 1 and 15, and MBDA score was assessed at baseline and 6 months.

MBDA scores correlated significantly with change from baseline to 6 months in DAS28-ESR (r = 0.60), DAS28–high-sensitivity C-reactive protein, (DAS28-hsCRP; r = 0.48), ESR (r = 0.48), and hsCRP (r = 0.71), and with European League Against Rheumatism (EULAR) good or moderate response at 6 months based on DAS28-ESR (adjusted odds ratio, 0.91).

Extensive work has been done to validate the MBDA score for assessing disease activity, and it has been shown to perform well for predicting response to a variety of disease-modifying antirheumatic drugs and biologic agents, Dr. Hitraya explained.

Additionally, multiple studies have demonstrated that the MBDA score defines risk categories for radiographic progression and performs better than traditional measures of disease activity for identifying those at increased risk of radiographic progression, which can help physicians mitigate associated risks through increased surveillance and therapeutic choices, she said.

“Having data for these specific molecules [tofacitinib and rituximab] is very important for rheumatologists,” Dr. Hitraya said.

The tofacitinib study was supported by Pfizer. Dr. Razmjou and Dr. Roodenrijs each reported having no disclosures.

sworcester@mdedge.com

SOURCE: Razmjou A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 582; Roodenrijs N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1500.

CHICAGO – The commercially available multibiomarker disease activity score assay and power Doppler ultrasound at baseline in rheumatoid arthritis patients treated with tofacitinib predicted 12-week responses on some clinical, imaging, and biomarker endpoints, according to findings from an investigator-initiated, open-label study.

The blood test–based multibiomarker disease activity (MBDA) score, which is calculated using measurements of 12 inflammatory biomarkers to score RA disease activity on a 0-100 point scale (Vectra DA, Myriad Autoimmune), also appears to track RA patients’ responses to rituximab, according to a post-hoc analysis of three cohort studies.

The findings of both studies were presented in posters at the annual meeting of the American College of Rheumatology. They are the first studies to evaluate early musculoskeletal ultrasound (MSUS) and MBDA score changes as predictors of response to tofacitinib in patients with RA, and the first to assess the ability of the MBDA score to track response to rituximab treatment. They provide valuable information that can help guide patient treatment and thereby improve outcomes, Elena Hitraya, MD, PhD, chief medical officer for Crescendo Bioscience/Myriad Autoimmune, San Francisco, said in an interview.

In the tofacitinib study, 25 RA patients with a mean age of 52 years, mean disease duration of 10.4 years, baseline Disease Activity Score 28-joint count (DAS28) greater than 3.2, and power Doppler ultrasound (PDUS) scores greater than 10 were treated with the approved oral tofacitinib dose of 5 mg twice daily. Assessments at baseline, 2 weeks, and 12 weeks included MSUS to score 34 joints for PDUS and gray scale ultrasound (GSUS), MBDA score, clinical disease activity index (CDAI), and DAS28, according to Amir Razmjou, MD, of the University of California, Los Angeles, and his colleagues.

Statistically significant improvement was seen on all measures over the 12-week study period (all at P less than .0001). For example, from baseline to 12 weeks the PDUS score improved from 28.6 to 12.2, GSUS score improved from 48.4 to 37.9, MBDA score improved from 50.6 to 39.6, CDAI score improved from 39.9 to 21.6, and DAS28–erythrocyte sedimentation rate (DAS28-ESR) score improved from 6.3 to 4.6, they said, noting further that baseline PDUS and MBDA scores significantly predicted CDAI and DAS28 responses at 12 weeks (P less than .01).

In the rituximab study, the MBDA score tracked disease activity in 57 RA patients from three different cohorts with a mean age of 57 years and mean disease duration of 11.5 years. Changes in the MBDA score reflected the degree of treatment response, Nadia M.T. Roodenrijs of University Medical Center Utrecht (the Netherlands) and her colleagues reported.

All patients were treated with 1,000 mg rituximab and 100 mg methylprednisolone on days 1 and 15, and MBDA score was assessed at baseline and 6 months.

MBDA scores correlated significantly with change from baseline to 6 months in DAS28-ESR (r = 0.60), DAS28–high-sensitivity C-reactive protein, (DAS28-hsCRP; r = 0.48), ESR (r = 0.48), and hsCRP (r = 0.71), and with European League Against Rheumatism (EULAR) good or moderate response at 6 months based on DAS28-ESR (adjusted odds ratio, 0.91).

Extensive work has been done to validate the MBDA score for assessing disease activity, and it has been shown to perform well for predicting response to a variety of disease-modifying antirheumatic drugs and biologic agents, Dr. Hitraya explained.

Additionally, multiple studies have demonstrated that the MBDA score defines risk categories for radiographic progression and performs better than traditional measures of disease activity for identifying those at increased risk of radiographic progression, which can help physicians mitigate associated risks through increased surveillance and therapeutic choices, she said.

“Having data for these specific molecules [tofacitinib and rituximab] is very important for rheumatologists,” Dr. Hitraya said.

The tofacitinib study was supported by Pfizer. Dr. Razmjou and Dr. Roodenrijs each reported having no disclosures.

sworcester@mdedge.com

SOURCE: Razmjou A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 582; Roodenrijs N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1500.

CHICAGO – Discontinuing methotrexate for 2 weeks in patients with RA starting the day they receive the seasonal influenza vaccine significantly improves the vaccine’s immunogenicity without aggravating disease activity, Kevin L. Winthrop, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“I think this is potentially clinically practice changing because now there are two studies showing the same thing,” said Dr. Winthrop, a professor of public health and preventive medicine at Oregon Health & Science University, Portland.

Based upon these prospective randomized studies, which he conducted together with investigators at Seoul National University in South Korea, initiating a 2-week halt of methotrexate on the day the influenza vaccine is given to patients with RA is now his routine practice, and he recommends other physicians do the same.


The first prospective, randomized trial included 199 RA patients on stable doses of methotrexate who were assigned to one of four groups in conjunction with seasonal influenza vaccination. One group continued their methotrexate as usual, the second stopped the drug for 1 month prior to vaccination and then restarted it at the time of vaccination, the third group halted methotrexate for 2 weeks before and 2 weeks after vaccination, and the fourth suspended methotrexate for 4 weeks starting on the day they got their flu shot. Everyone received trivalent influenza vaccine containing H1N1, H3N2, and B/Yamagata.

The lowest rate of satisfactory vaccine response as defined by at least a 300% titer increase 1 month after vaccination occurred in the group that continued their methotrexate as usual. The group that halted the drug for 2 weeks before and 2 weeks after influenza vaccination had a 51% satisfactory vaccine response against all three antigens, compared with a 31.5% rate in the methotrexate-as-usual group. RA flare rates ranged from 21% to 39% across the four study arms, differences that weren’t statistically significant (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).

Next Dr. Winthrop and his colleagues conducted a confirmatory prospective, multicenter, randomized trial in which they sought to nail down the optimal duration and timing of methotrexate discontinuation. A total of 320 RA patients on stable doses of methotrexate were assigned to halt the drug for 2 weeks starting at the time they received a quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains, or to continue their methotrexate throughout.

A satisfactory vaccine response was achieved in 75.5% of the group that discontinued the drug, significantly better than the 54.5% rate in the methotrexate continuers. The absolute difference in seroprotection was greater in patients who halted their methotrexate for 2 weeks after vaccination for all four antigens: an absolute 11% difference for H1N1, 16% for H3N2, 12% for B/Yamagata, and 15% for B/Victoria (Ann Rheum Dis. 2018 Jun;77[6]:898-904).

“It does seem to be a nice strategy. The percentage of people who flared their RA during their 2 weeks off methotrexate was very low, so there seems to be a good reason to do this,” according to Dr. Winthrop.


Some rheumatologists he has spoken with initially balked at the plausibility of the results.

“I had the same thought about these studies: It doesn’t make sense to me in terms of how methotrexate works, and why we would see this effect acutely by stopping methotrexate for just 2 weeks?” he said.

But then a coinvestigator drilled down deeper into the data and came up with the explanation: The benefit in terms of enhanced flu vaccine immunogenicity through temporary withholding of methotrexate was confined to the subgroup of RA patients with high baseline levels of B-cell activation factor (BAFF). In contrast, withholding methotrexate didn’t affect the vaccine response in patients with low or normal baseline BAFF (Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214025).

“I don’t know how to check anyone’s BAFF levels. I don’t think there’s a commercial test out there. But this does help explain why we saw this observation. So I think I would still hold everyone’s methotrexate for 2 weeks. That’s how I approach it. And they may get benefit from it, and they may not,” he said.

Dr. Winthrop reported having no financial conflicts regarding the study, which was funded by GC Pharma.

bjancin@mdedge.com

CHICAGO – Discontinuing methotrexate for 2 weeks in patients with RA starting the day they receive the seasonal influenza vaccine significantly improves the vaccine’s immunogenicity without aggravating disease activity, Kevin L. Winthrop, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“I think this is potentially clinically practice changing because now there are two studies showing the same thing,” said Dr. Winthrop, a professor of public health and preventive medicine at Oregon Health & Science University, Portland.

Based upon these prospective randomized studies, which he conducted together with investigators at Seoul National University in South Korea, initiating a 2-week halt of methotrexate on the day the influenza vaccine is given to patients with RA is now his routine practice, and he recommends other physicians do the same.


The first prospective, randomized trial included 199 RA patients on stable doses of methotrexate who were assigned to one of four groups in conjunction with seasonal influenza vaccination. One group continued their methotrexate as usual, the second stopped the drug for 1 month prior to vaccination and then restarted it at the time of vaccination, the third group halted methotrexate for 2 weeks before and 2 weeks after vaccination, and the fourth suspended methotrexate for 4 weeks starting on the day they got their flu shot. Everyone received trivalent influenza vaccine containing H1N1, H3N2, and B/Yamagata.

The lowest rate of satisfactory vaccine response as defined by at least a 300% titer increase 1 month after vaccination occurred in the group that continued their methotrexate as usual. The group that halted the drug for 2 weeks before and 2 weeks after influenza vaccination had a 51% satisfactory vaccine response against all three antigens, compared with a 31.5% rate in the methotrexate-as-usual group. RA flare rates ranged from 21% to 39% across the four study arms, differences that weren’t statistically significant (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).

Next Dr. Winthrop and his colleagues conducted a confirmatory prospective, multicenter, randomized trial in which they sought to nail down the optimal duration and timing of methotrexate discontinuation. A total of 320 RA patients on stable doses of methotrexate were assigned to halt the drug for 2 weeks starting at the time they received a quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains, or to continue their methotrexate throughout.

A satisfactory vaccine response was achieved in 75.5% of the group that discontinued the drug, significantly better than the 54.5% rate in the methotrexate continuers. The absolute difference in seroprotection was greater in patients who halted their methotrexate for 2 weeks after vaccination for all four antigens: an absolute 11% difference for H1N1, 16% for H3N2, 12% for B/Yamagata, and 15% for B/Victoria (Ann Rheum Dis. 2018 Jun;77[6]:898-904).

“It does seem to be a nice strategy. The percentage of people who flared their RA during their 2 weeks off methotrexate was very low, so there seems to be a good reason to do this,” according to Dr. Winthrop.


Some rheumatologists he has spoken with initially balked at the plausibility of the results.

“I had the same thought about these studies: It doesn’t make sense to me in terms of how methotrexate works, and why we would see this effect acutely by stopping methotrexate for just 2 weeks?” he said.

But then a coinvestigator drilled down deeper into the data and came up with the explanation: The benefit in terms of enhanced flu vaccine immunogenicity through temporary withholding of methotrexate was confined to the subgroup of RA patients with high baseline levels of B-cell activation factor (BAFF). In contrast, withholding methotrexate didn’t affect the vaccine response in patients with low or normal baseline BAFF (Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214025).

“I don’t know how to check anyone’s BAFF levels. I don’t think there’s a commercial test out there. But this does help explain why we saw this observation. So I think I would still hold everyone’s methotrexate for 2 weeks. That’s how I approach it. And they may get benefit from it, and they may not,” he said.

Dr. Winthrop reported having no financial conflicts regarding the study, which was funded by GC Pharma.

bjancin@mdedge.com

CHICAGO – Discontinuing methotrexate for 2 weeks in patients with RA starting the day they receive the seasonal influenza vaccine significantly improves the vaccine’s immunogenicity without aggravating disease activity, Kevin L. Winthrop, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“I think this is potentially clinically practice changing because now there are two studies showing the same thing,” said Dr. Winthrop, a professor of public health and preventive medicine at Oregon Health & Science University, Portland.

Based upon these prospective randomized studies, which he conducted together with investigators at Seoul National University in South Korea, initiating a 2-week halt of methotrexate on the day the influenza vaccine is given to patients with RA is now his routine practice, and he recommends other physicians do the same.


The first prospective, randomized trial included 199 RA patients on stable doses of methotrexate who were assigned to one of four groups in conjunction with seasonal influenza vaccination. One group continued their methotrexate as usual, the second stopped the drug for 1 month prior to vaccination and then restarted it at the time of vaccination, the third group halted methotrexate for 2 weeks before and 2 weeks after vaccination, and the fourth suspended methotrexate for 4 weeks starting on the day they got their flu shot. Everyone received trivalent influenza vaccine containing H1N1, H3N2, and B/Yamagata.

The lowest rate of satisfactory vaccine response as defined by at least a 300% titer increase 1 month after vaccination occurred in the group that continued their methotrexate as usual. The group that halted the drug for 2 weeks before and 2 weeks after influenza vaccination had a 51% satisfactory vaccine response against all three antigens, compared with a 31.5% rate in the methotrexate-as-usual group. RA flare rates ranged from 21% to 39% across the four study arms, differences that weren’t statistically significant (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).

Next Dr. Winthrop and his colleagues conducted a confirmatory prospective, multicenter, randomized trial in which they sought to nail down the optimal duration and timing of methotrexate discontinuation. A total of 320 RA patients on stable doses of methotrexate were assigned to halt the drug for 2 weeks starting at the time they received a quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains, or to continue their methotrexate throughout.

A satisfactory vaccine response was achieved in 75.5% of the group that discontinued the drug, significantly better than the 54.5% rate in the methotrexate continuers. The absolute difference in seroprotection was greater in patients who halted their methotrexate for 2 weeks after vaccination for all four antigens: an absolute 11% difference for H1N1, 16% for H3N2, 12% for B/Yamagata, and 15% for B/Victoria (Ann Rheum Dis. 2018 Jun;77[6]:898-904).

“It does seem to be a nice strategy. The percentage of people who flared their RA during their 2 weeks off methotrexate was very low, so there seems to be a good reason to do this,” according to Dr. Winthrop.


Some rheumatologists he has spoken with initially balked at the plausibility of the results.

“I had the same thought about these studies: It doesn’t make sense to me in terms of how methotrexate works, and why we would see this effect acutely by stopping methotrexate for just 2 weeks?” he said.

But then a coinvestigator drilled down deeper into the data and came up with the explanation: The benefit in terms of enhanced flu vaccine immunogenicity through temporary withholding of methotrexate was confined to the subgroup of RA patients with high baseline levels of B-cell activation factor (BAFF). In contrast, withholding methotrexate didn’t affect the vaccine response in patients with low or normal baseline BAFF (Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214025).

“I don’t know how to check anyone’s BAFF levels. I don’t think there’s a commercial test out there. But this does help explain why we saw this observation. So I think I would still hold everyone’s methotrexate for 2 weeks. That’s how I approach it. And they may get benefit from it, and they may not,” he said.

Dr. Winthrop reported having no financial conflicts regarding the study, which was funded by GC Pharma.

bjancin@mdedge.com

Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimilar of Rituxan.

Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

GP2013 already is approved in the European Union and elsewhere.

The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.

At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.

“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.

“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”

The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).

The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.

At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.

jensmith@mdedge.com

Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimilar of Rituxan.

Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

GP2013 already is approved in the European Union and elsewhere.

The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.

At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.

“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.

“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”

The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).

The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.

At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.

jensmith@mdedge.com

Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimilar of Rituxan.

Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

GP2013 already is approved in the European Union and elsewhere.

The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.

At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.

“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.

“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”

The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).

The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.

At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.

jensmith@mdedge.com

CHICAGO – Patients with an inflammatory arthritis had significantly higher rates of infections, transfusions, and readmissions following total knee replacement than did patients without inflammatory arthritis in a study of more than 137,000 Americans who underwent this surgery.

A sampling of U.S. patients who underwent total knee arthroplasty (TKA) during 2007-2016 showed that among the small percentage of these patients who had an inflammatory arthritis (IA), the rate of periprosthetic joint or wound infection while hospitalized or out to 30 days after surgery was a statistically significant 64% higher relative to patients without inflammatory arthritis, after adjustment for several demographic and clinical confounders, including recent glucocorticoid treatment, Susan M. Goodman, MD, said at the annual meeting of the American College of Rheumatology. The analysis also showed a statistically significant 46% higher relative rate of hospital readmission for any cause during the 90 days after surgery, and a significant 39% relative increase in blood transfusions during the 30 days after TKA in the IA patients.

“These results have important implications for evolving bundled payment models” for TKA, said Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York. “Hospitals should receive commensurate resources to maintain access to total TKA for patients with IA.”

For this analysis, Dr. Goodman and her associates classified IA as a patient with a recorded diagnosis of rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus if the patient had also received treatment during the year before surgery with a disease-modifying antirheumatic drug, a biologic agent, or a drug that treats systemic lupus erythematosus.

Complications following TKA became a particular concern to hospitals starting in 2013 when the Centers for Medicare & Medicaid Services began a program that penalized hospitals for outcomes such as excessive readmissions following selected types of hospitalizations and also with recent steps to bundle TKA reimbursement with related 90-day outcomes.

“My concern is to ensure that patients with IA aren’t penalized and can maintain access” to TKA despite recent policy moves by the CMS. Faced with potential disincentives to treat patients with an IA, “hospitals might cherry pick patients,” Dr. Goodman said in an interview. The new findings “are a reason for administrators to argue for patients with IA to come out of the cost bundle.”

Dr. Goodman expressed hope that future policies will better reflect the higher levels of risk faced by patients with an IA undergoing TKA. CMS “is pretty responsive,” she said.

The study used data collected by Humana for about 25 million American health insurance beneficiaries during 2007-2016, which included 137,550 people who underwent a TKA. Of these, 3,067 (2%) met the study’s definition for IA, and 134,483 did not. Most of those who did not meet the definition likely had osteoarthritis, Dr. Goodman said. This low percentage of U.S. TKA patients with IA was consistent with numbers in prior reports.

The researchers calculated the relative risk of the IA patients, compared with all the others, for nine potential complications, including acute MI, pneumonia, sepsis, pulmonary embolism, and death. The complications with significantly higher rates among the IA patients after confounder adjustment were 30-day infections, 30-day transfusions, and 90-day readmissions.

Dr. Goodman had no relevant disclosures.

mzoler@mdedge.com

SOURCE: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.

CHICAGO – Patients with an inflammatory arthritis had significantly higher rates of infections, transfusions, and readmissions following total knee replacement than did patients without inflammatory arthritis in a study of more than 137,000 Americans who underwent this surgery.

A sampling of U.S. patients who underwent total knee arthroplasty (TKA) during 2007-2016 showed that among the small percentage of these patients who had an inflammatory arthritis (IA), the rate of periprosthetic joint or wound infection while hospitalized or out to 30 days after surgery was a statistically significant 64% higher relative to patients without inflammatory arthritis, after adjustment for several demographic and clinical confounders, including recent glucocorticoid treatment, Susan M. Goodman, MD, said at the annual meeting of the American College of Rheumatology. The analysis also showed a statistically significant 46% higher relative rate of hospital readmission for any cause during the 90 days after surgery, and a significant 39% relative increase in blood transfusions during the 30 days after TKA in the IA patients.

“These results have important implications for evolving bundled payment models” for TKA, said Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York. “Hospitals should receive commensurate resources to maintain access to total TKA for patients with IA.”

For this analysis, Dr. Goodman and her associates classified IA as a patient with a recorded diagnosis of rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus if the patient had also received treatment during the year before surgery with a disease-modifying antirheumatic drug, a biologic agent, or a drug that treats systemic lupus erythematosus.

Complications following TKA became a particular concern to hospitals starting in 2013 when the Centers for Medicare & Medicaid Services began a program that penalized hospitals for outcomes such as excessive readmissions following selected types of hospitalizations and also with recent steps to bundle TKA reimbursement with related 90-day outcomes.

“My concern is to ensure that patients with IA aren’t penalized and can maintain access” to TKA despite recent policy moves by the CMS. Faced with potential disincentives to treat patients with an IA, “hospitals might cherry pick patients,” Dr. Goodman said in an interview. The new findings “are a reason for administrators to argue for patients with IA to come out of the cost bundle.”

Dr. Goodman expressed hope that future policies will better reflect the higher levels of risk faced by patients with an IA undergoing TKA. CMS “is pretty responsive,” she said.

The study used data collected by Humana for about 25 million American health insurance beneficiaries during 2007-2016, which included 137,550 people who underwent a TKA. Of these, 3,067 (2%) met the study’s definition for IA, and 134,483 did not. Most of those who did not meet the definition likely had osteoarthritis, Dr. Goodman said. This low percentage of U.S. TKA patients with IA was consistent with numbers in prior reports.

The researchers calculated the relative risk of the IA patients, compared with all the others, for nine potential complications, including acute MI, pneumonia, sepsis, pulmonary embolism, and death. The complications with significantly higher rates among the IA patients after confounder adjustment were 30-day infections, 30-day transfusions, and 90-day readmissions.

Dr. Goodman had no relevant disclosures.

mzoler@mdedge.com

SOURCE: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.

CHICAGO – Patients with an inflammatory arthritis had significantly higher rates of infections, transfusions, and readmissions following total knee replacement than did patients without inflammatory arthritis in a study of more than 137,000 Americans who underwent this surgery.

A sampling of U.S. patients who underwent total knee arthroplasty (TKA) during 2007-2016 showed that among the small percentage of these patients who had an inflammatory arthritis (IA), the rate of periprosthetic joint or wound infection while hospitalized or out to 30 days after surgery was a statistically significant 64% higher relative to patients without inflammatory arthritis, after adjustment for several demographic and clinical confounders, including recent glucocorticoid treatment, Susan M. Goodman, MD, said at the annual meeting of the American College of Rheumatology. The analysis also showed a statistically significant 46% higher relative rate of hospital readmission for any cause during the 90 days after surgery, and a significant 39% relative increase in blood transfusions during the 30 days after TKA in the IA patients.

“These results have important implications for evolving bundled payment models” for TKA, said Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York. “Hospitals should receive commensurate resources to maintain access to total TKA for patients with IA.”

For this analysis, Dr. Goodman and her associates classified IA as a patient with a recorded diagnosis of rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus if the patient had also received treatment during the year before surgery with a disease-modifying antirheumatic drug, a biologic agent, or a drug that treats systemic lupus erythematosus.

Complications following TKA became a particular concern to hospitals starting in 2013 when the Centers for Medicare & Medicaid Services began a program that penalized hospitals for outcomes such as excessive readmissions following selected types of hospitalizations and also with recent steps to bundle TKA reimbursement with related 90-day outcomes.

“My concern is to ensure that patients with IA aren’t penalized and can maintain access” to TKA despite recent policy moves by the CMS. Faced with potential disincentives to treat patients with an IA, “hospitals might cherry pick patients,” Dr. Goodman said in an interview. The new findings “are a reason for administrators to argue for patients with IA to come out of the cost bundle.”

Dr. Goodman expressed hope that future policies will better reflect the higher levels of risk faced by patients with an IA undergoing TKA. CMS “is pretty responsive,” she said.

The study used data collected by Humana for about 25 million American health insurance beneficiaries during 2007-2016, which included 137,550 people who underwent a TKA. Of these, 3,067 (2%) met the study’s definition for IA, and 134,483 did not. Most of those who did not meet the definition likely had osteoarthritis, Dr. Goodman said. This low percentage of U.S. TKA patients with IA was consistent with numbers in prior reports.

The researchers calculated the relative risk of the IA patients, compared with all the others, for nine potential complications, including acute MI, pneumonia, sepsis, pulmonary embolism, and death. The complications with significantly higher rates among the IA patients after confounder adjustment were 30-day infections, 30-day transfusions, and 90-day readmissions.

Dr. Goodman had no relevant disclosures.

mzoler@mdedge.com

SOURCE: Richardson S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1932.

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

lfranki@mdedge.com

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

lfranki@mdedge.com

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

lfranki@mdedge.com

CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.

Mitchel L. Zoler/MDedge News

The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.

Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m², and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.

The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.

The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.

As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.

Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.

PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.

mzoler@mdedge.com

SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).

CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.

Mitchel L. Zoler/MDedge News

The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.

Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m², and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.

The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.

The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.

As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.

Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.

PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.

mzoler@mdedge.com

SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).

CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.

Mitchel L. Zoler/MDedge News

The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.

Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m², and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.

The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.

The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.

As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.

Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.

PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.

mzoler@mdedge.com

SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com