Neil Osterweil

SAN FRANCISCO – Unless there is a clear contraindication to anticoagulation therapy, cancer patients who have an incidental pulmonary embolism discovered during imaging studies should receive chronic anticoagulation, preferably with a low-molecular-weight heparin, based on study results presented at the annual meeting of the American Society of Hematology.

Without anticoagulation therapy, the risk for a recurent venous thromboembolic event was fourfold higher among 926 cancer patients who had a pulmonary embolism discovered during CT imaging for reasons other than suspicion of pulmonary embolism (PE), according to Dr. Tom van der Hulle of Leiden (the Netherlands) University Medical Center.

Among cancer patients who did receive an anticoagulant, low-molecular-weight heparin (LMWH) was significantly better than warfarin at preventing recurrent venous thromboembolism (VTE) or PE. Compared with warfarin, LMWH also was associated with a significantly lower risk for bleeding.

“Our study confirms the high risk of recurrent [VTE] in patients with cancer-associated incidental pulmonary embolism, but it also provides outcomes if patients are left untreated,” Dr. van der Hulle said at a briefing prior to his presentation of the data.

Risk for primary and recurrent VTE is particularly high for patients with pancreatic cancer, lung cancer, metastatic adenocarcinoma of gastroinestinal or gynecologic origin, and brain tumors, noted Dr. Agnes Lee of the University of British Columbia in Vancouver. Dr. Lee also presented data at the briefing but was not involved with the study.

“Once the patients are started on treatment for their clotting episode, for a DVT or PE, a minimum of 3-6 months of anticoagulation is recommended. After that, we look at patients to see whether they have ongoing reasons to develop recurrent thrombosis. So this would be patients who have active cancer – they’re still receiving chemotherapy, they have obvious evidence of cancer or metastatic disease, or they’re sick for other reasons. These are patients who would then continue on anticoagulant therapy,” she added.

Dr. van der Hulle and his colleagues conducted a pooled meta-analysis of 926 patients with cancer who had an incidental PE discovered during a CT scan. The researchers compared results for patients treated with LMWH (79%), a vitamin K antagonist (predominantly warfarin, 11%), and for those who did not receive prophylaxis with an anticoagualant because of contraindications.

They looked at recurrent VTE, major bleeding episodes, and death at 6 months and conducted subgroup analyses based on patient management and thrombus location.

Patients with metastatic disease comprised 74% of those treated with LMWH, 62% of those treated with a vitamin K antagonist, and 73% of untreated patients.

The overall pooled 6-month risk of symptomatic recurrent VTE was 5.8%. The risk of major bleeding was 4.7%, and the risk of death was 37%.

Risk of recurrent VTE was 6.2% for patients treated with LMWH and 6.4% for those treated with a vitamin K antagonist. Recurrent VTE risk was 12% for untreated patients.

Major bleeding was seen in 3.9% of LMWH-treated patients and in 13% of vitamin K antagonist–treated patients (hazard ratio 3.9; 95% confidence interval, 1.6-10).The 6-month mortality rates were 37% for patients treated with LMWH, 28% for those treated with warfarin or a related drug, and 47% for untreated patients.

When the authors looked at the location of the thrombus – isolated subsegmental incidental PE vs. central PE – they found that the risk of recurrent isolated embolism was 7.8% and for central embolism was 5.5%.

Dr. van der Hulle said that the findings of this observational study should preferably be confirmed in a randomized trial, but acknowledged that, given the risk of no treatment, a placebo-controlled trial might be considered unethical.

The study was internally supported. Dr. van der Hulle and Dr. Lee reported no relevant conflicts of interest.

SAN FRANCISCO – Unless there is a clear contraindication to anticoagulation therapy, cancer patients who have an incidental pulmonary embolism discovered during imaging studies should receive chronic anticoagulation, preferably with a low-molecular-weight heparin, based on study results presented at the annual meeting of the American Society of Hematology.

Without anticoagulation therapy, the risk for a recurent venous thromboembolic event was fourfold higher among 926 cancer patients who had a pulmonary embolism discovered during CT imaging for reasons other than suspicion of pulmonary embolism (PE), according to Dr. Tom van der Hulle of Leiden (the Netherlands) University Medical Center.

Among cancer patients who did receive an anticoagulant, low-molecular-weight heparin (LMWH) was significantly better than warfarin at preventing recurrent venous thromboembolism (VTE) or PE. Compared with warfarin, LMWH also was associated with a significantly lower risk for bleeding.

“Our study confirms the high risk of recurrent [VTE] in patients with cancer-associated incidental pulmonary embolism, but it also provides outcomes if patients are left untreated,” Dr. van der Hulle said at a briefing prior to his presentation of the data.

Risk for primary and recurrent VTE is particularly high for patients with pancreatic cancer, lung cancer, metastatic adenocarcinoma of gastroinestinal or gynecologic origin, and brain tumors, noted Dr. Agnes Lee of the University of British Columbia in Vancouver. Dr. Lee also presented data at the briefing but was not involved with the study.

“Once the patients are started on treatment for their clotting episode, for a DVT or PE, a minimum of 3-6 months of anticoagulation is recommended. After that, we look at patients to see whether they have ongoing reasons to develop recurrent thrombosis. So this would be patients who have active cancer – they’re still receiving chemotherapy, they have obvious evidence of cancer or metastatic disease, or they’re sick for other reasons. These are patients who would then continue on anticoagulant therapy,” she added.

Dr. van der Hulle and his colleagues conducted a pooled meta-analysis of 926 patients with cancer who had an incidental PE discovered during a CT scan. The researchers compared results for patients treated with LMWH (79%), a vitamin K antagonist (predominantly warfarin, 11%), and for those who did not receive prophylaxis with an anticoagualant because of contraindications.

They looked at recurrent VTE, major bleeding episodes, and death at 6 months and conducted subgroup analyses based on patient management and thrombus location.

Patients with metastatic disease comprised 74% of those treated with LMWH, 62% of those treated with a vitamin K antagonist, and 73% of untreated patients.

The overall pooled 6-month risk of symptomatic recurrent VTE was 5.8%. The risk of major bleeding was 4.7%, and the risk of death was 37%.

Risk of recurrent VTE was 6.2% for patients treated with LMWH and 6.4% for those treated with a vitamin K antagonist. Recurrent VTE risk was 12% for untreated patients.

Major bleeding was seen in 3.9% of LMWH-treated patients and in 13% of vitamin K antagonist–treated patients (hazard ratio 3.9; 95% confidence interval, 1.6-10).The 6-month mortality rates were 37% for patients treated with LMWH, 28% for those treated with warfarin or a related drug, and 47% for untreated patients.

When the authors looked at the location of the thrombus – isolated subsegmental incidental PE vs. central PE – they found that the risk of recurrent isolated embolism was 7.8% and for central embolism was 5.5%.

Dr. van der Hulle said that the findings of this observational study should preferably be confirmed in a randomized trial, but acknowledged that, given the risk of no treatment, a placebo-controlled trial might be considered unethical.

The study was internally supported. Dr. van der Hulle and Dr. Lee reported no relevant conflicts of interest.

SAN FRANCISCO – Unless there is a clear contraindication to anticoagulation therapy, cancer patients who have an incidental pulmonary embolism discovered during imaging studies should receive chronic anticoagulation, preferably with a low-molecular-weight heparin, based on study results presented at the annual meeting of the American Society of Hematology.

Without anticoagulation therapy, the risk for a recurent venous thromboembolic event was fourfold higher among 926 cancer patients who had a pulmonary embolism discovered during CT imaging for reasons other than suspicion of pulmonary embolism (PE), according to Dr. Tom van der Hulle of Leiden (the Netherlands) University Medical Center.

Among cancer patients who did receive an anticoagulant, low-molecular-weight heparin (LMWH) was significantly better than warfarin at preventing recurrent venous thromboembolism (VTE) or PE. Compared with warfarin, LMWH also was associated with a significantly lower risk for bleeding.

“Our study confirms the high risk of recurrent [VTE] in patients with cancer-associated incidental pulmonary embolism, but it also provides outcomes if patients are left untreated,” Dr. van der Hulle said at a briefing prior to his presentation of the data.

Risk for primary and recurrent VTE is particularly high for patients with pancreatic cancer, lung cancer, metastatic adenocarcinoma of gastroinestinal or gynecologic origin, and brain tumors, noted Dr. Agnes Lee of the University of British Columbia in Vancouver. Dr. Lee also presented data at the briefing but was not involved with the study.

“Once the patients are started on treatment for their clotting episode, for a DVT or PE, a minimum of 3-6 months of anticoagulation is recommended. After that, we look at patients to see whether they have ongoing reasons to develop recurrent thrombosis. So this would be patients who have active cancer – they’re still receiving chemotherapy, they have obvious evidence of cancer or metastatic disease, or they’re sick for other reasons. These are patients who would then continue on anticoagulant therapy,” she added.

Dr. van der Hulle and his colleagues conducted a pooled meta-analysis of 926 patients with cancer who had an incidental PE discovered during a CT scan. The researchers compared results for patients treated with LMWH (79%), a vitamin K antagonist (predominantly warfarin, 11%), and for those who did not receive prophylaxis with an anticoagualant because of contraindications.

They looked at recurrent VTE, major bleeding episodes, and death at 6 months and conducted subgroup analyses based on patient management and thrombus location.

Patients with metastatic disease comprised 74% of those treated with LMWH, 62% of those treated with a vitamin K antagonist, and 73% of untreated patients.

The overall pooled 6-month risk of symptomatic recurrent VTE was 5.8%. The risk of major bleeding was 4.7%, and the risk of death was 37%.

Risk of recurrent VTE was 6.2% for patients treated with LMWH and 6.4% for those treated with a vitamin K antagonist. Recurrent VTE risk was 12% for untreated patients.

Major bleeding was seen in 3.9% of LMWH-treated patients and in 13% of vitamin K antagonist–treated patients (hazard ratio 3.9; 95% confidence interval, 1.6-10).The 6-month mortality rates were 37% for patients treated with LMWH, 28% for those treated with warfarin or a related drug, and 47% for untreated patients.

When the authors looked at the location of the thrombus – isolated subsegmental incidental PE vs. central PE – they found that the risk of recurrent isolated embolism was 7.8% and for central embolism was 5.5%.

Dr. van der Hulle said that the findings of this observational study should preferably be confirmed in a randomized trial, but acknowledged that, given the risk of no treatment, a placebo-controlled trial might be considered unethical.

The study was internally supported. Dr. van der Hulle and Dr. Lee reported no relevant conflicts of interest.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

SAN FRANCISCO – New standards of care are hard to come by in the treatment of relapsed/refractory multiple myeloma, but interim results of a phase III trial of the combination of carfilzomib, lenalidomide, and dexamethasone suggest that it might just fit the bill, investigators say.

In a randomized controlled trial comparing the combination, the comination, labeled KRd (the K is for carfilzomib’s tradename, Kyrpolis), was associated with significantly better progression-free survival (PFS) and a trend toward better overall survival than lenalidomide (Revlimid) and dexamethasone combined (RD), reported Dr. A. Keith Stewart, principal investigator and dean for research at the Mayo Clinic in Scottsdale, Arizona, at the annual meeting of the American Society of Hematology.

“Dr. Stewart’s study will, I think, establish a new standard of care in this patient population,” commented Dr. Brad Kahl of the University of Wisconsin School of Medicine and Public Health in Madison, who moderated a briefing where the data were presented. They were published simultaneously online in the New England Journal of Medicine (NEJM, Dec. 6, 2014 [DOI: 10.1056/NEJMoa1411321]).

Neil Osterweil/Frontline Medical News

Among 792 patients with relapsed/refractory multiple myeloma, PFS with patients randomized to receive KRd was 26.3 months, compared with 17.6 months for patients randomized to RD. The hazard ratio for progression or death with KRd was 0.69 (P = .0001, crossing the pre-specified stopping boundary). Median overall survival had not been reached for either group. Kaplan-Meier 24 month overall survival rates were 73.3% and 65.0%, respec-tively, trending in favor of KRd, but with a P value (.04) that did not meet the pre-specified stopping boundary for survival (P = .005).

“In this same population of patients – this is patients who have relapsed one, two or three times – the best result ever reported before with any combina-tion of chemotherapy was about 19 months, with a very similar cocktail of bortezomib, thalidomide and dexamethasone,” Dr. Stewart said at the briefing.

Neil Osterweil/Frontline Medical News

The KRd combination also appeared to be safe.

“Despite the fact that we added a third drug and patients were on treatment significantly longer, there was a fairly well balanced ratio of patients who had to discontinue treatment due to side effects. It’s important to note that cardiac and renal events which have been reported in some studies of heavily pre-treated patients [with carfilzomib] in the past, were marginally higher in the three-drug regimen, but overall were very consistent or even lower than had previously been reported [with single-agent carilzomib],” Dr. Stewart said.

Carfilzomib is an epoxyketone proteasome inhibitor that binds selectively to the constitutive proteasome and immunoproteasome. Unlike the first-in-class proteasome inhibitor, bortezomib (Velcade), carfilzomib irreversibly binds to and disables its targets, Dr. Stewart said in an interview.

In the ASPIRE (Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone for the Treatment of Patients with Relapsed Multiple Myeloma) trial, investigators enrolled 792 adults with relapsed multiple myeloma from 20 countries in North America, Europe, and the Middle East. The patients, who had previously received 1-3 prior lines of therapy, were randomly assigned to receive either KRd (carfilzomib 20 mg/m2 on days 1 and 2 of the first 28-day cycle, then 27 mg/m2 for days 8,9,15, and 16, and all days of subsequent cycles), oral lenolidamide 25 mg days 1-21, and oral dexamethasone days 1, 8, 15 and 22 of each cycle; or RD, which consisted of lenalidomide and dexamethasone in the same doses and on the same schedule as in KRd.

At the time of the data cutoff for the interim analysis in June 2014, 118 of 396 patients assigned to KRd were still on treatment, as were 86 of 396 in the RD group.

At the time of the analysis, 431 PFS events had been documented, and the study met its primary endpoint of superior PFS with the addition of carfilzomib.

Common adverse events, including diarrhea, cough, fever and hypertension were reported more frequently in the KRd group.

Remissions were more durable among patients who received carfilzomib, and these patients reported higher quality-of-life scores on the QLQ-C30 Global Health Status and Quality of Life scale, Dr. Stewart noted.

SAN FRANCISCO – New standards of care are hard to come by in the treatment of relapsed/refractory multiple myeloma, but interim results of a phase III trial of the combination of carfilzomib, lenalidomide, and dexamethasone suggest that it might just fit the bill, investigators say.

In a randomized controlled trial comparing the combination, the comination, labeled KRd (the K is for carfilzomib’s tradename, Kyrpolis), was associated with significantly better progression-free survival (PFS) and a trend toward better overall survival than lenalidomide (Revlimid) and dexamethasone combined (RD), reported Dr. A. Keith Stewart, principal investigator and dean for research at the Mayo Clinic in Scottsdale, Arizona, at the annual meeting of the American Society of Hematology.

“Dr. Stewart’s study will, I think, establish a new standard of care in this patient population,” commented Dr. Brad Kahl of the University of Wisconsin School of Medicine and Public Health in Madison, who moderated a briefing where the data were presented. They were published simultaneously online in the New England Journal of Medicine (NEJM, Dec. 6, 2014 [DOI: 10.1056/NEJMoa1411321]).

Neil Osterweil/Frontline Medical News

Among 792 patients with relapsed/refractory multiple myeloma, PFS with patients randomized to receive KRd was 26.3 months, compared with 17.6 months for patients randomized to RD. The hazard ratio for progression or death with KRd was 0.69 (P = .0001, crossing the pre-specified stopping boundary). Median overall survival had not been reached for either group. Kaplan-Meier 24 month overall survival rates were 73.3% and 65.0%, respec-tively, trending in favor of KRd, but with a P value (.04) that did not meet the pre-specified stopping boundary for survival (P = .005).

“In this same population of patients – this is patients who have relapsed one, two or three times – the best result ever reported before with any combina-tion of chemotherapy was about 19 months, with a very similar cocktail of bortezomib, thalidomide and dexamethasone,” Dr. Stewart said at the briefing.

Neil Osterweil/Frontline Medical News

The KRd combination also appeared to be safe.

“Despite the fact that we added a third drug and patients were on treatment significantly longer, there was a fairly well balanced ratio of patients who had to discontinue treatment due to side effects. It’s important to note that cardiac and renal events which have been reported in some studies of heavily pre-treated patients [with carfilzomib] in the past, were marginally higher in the three-drug regimen, but overall were very consistent or even lower than had previously been reported [with single-agent carilzomib],” Dr. Stewart said.

Carfilzomib is an epoxyketone proteasome inhibitor that binds selectively to the constitutive proteasome and immunoproteasome. Unlike the first-in-class proteasome inhibitor, bortezomib (Velcade), carfilzomib irreversibly binds to and disables its targets, Dr. Stewart said in an interview.

In the ASPIRE (Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone for the Treatment of Patients with Relapsed Multiple Myeloma) trial, investigators enrolled 792 adults with relapsed multiple myeloma from 20 countries in North America, Europe, and the Middle East. The patients, who had previously received 1-3 prior lines of therapy, were randomly assigned to receive either KRd (carfilzomib 20 mg/m2 on days 1 and 2 of the first 28-day cycle, then 27 mg/m2 for days 8,9,15, and 16, and all days of subsequent cycles), oral lenolidamide 25 mg days 1-21, and oral dexamethasone days 1, 8, 15 and 22 of each cycle; or RD, which consisted of lenalidomide and dexamethasone in the same doses and on the same schedule as in KRd.

At the time of the data cutoff for the interim analysis in June 2014, 118 of 396 patients assigned to KRd were still on treatment, as were 86 of 396 in the RD group.

At the time of the analysis, 431 PFS events had been documented, and the study met its primary endpoint of superior PFS with the addition of carfilzomib.

Common adverse events, including diarrhea, cough, fever and hypertension were reported more frequently in the KRd group.

Remissions were more durable among patients who received carfilzomib, and these patients reported higher quality-of-life scores on the QLQ-C30 Global Health Status and Quality of Life scale, Dr. Stewart noted.

SAN FRANCISCO – New standards of care are hard to come by in the treatment of relapsed/refractory multiple myeloma, but interim results of a phase III trial of the combination of carfilzomib, lenalidomide, and dexamethasone suggest that it might just fit the bill, investigators say.

In a randomized controlled trial comparing the combination, the comination, labeled KRd (the K is for carfilzomib’s tradename, Kyrpolis), was associated with significantly better progression-free survival (PFS) and a trend toward better overall survival than lenalidomide (Revlimid) and dexamethasone combined (RD), reported Dr. A. Keith Stewart, principal investigator and dean for research at the Mayo Clinic in Scottsdale, Arizona, at the annual meeting of the American Society of Hematology.

“Dr. Stewart’s study will, I think, establish a new standard of care in this patient population,” commented Dr. Brad Kahl of the University of Wisconsin School of Medicine and Public Health in Madison, who moderated a briefing where the data were presented. They were published simultaneously online in the New England Journal of Medicine (NEJM, Dec. 6, 2014 [DOI: 10.1056/NEJMoa1411321]).

Neil Osterweil/Frontline Medical News

Among 792 patients with relapsed/refractory multiple myeloma, PFS with patients randomized to receive KRd was 26.3 months, compared with 17.6 months for patients randomized to RD. The hazard ratio for progression or death with KRd was 0.69 (P = .0001, crossing the pre-specified stopping boundary). Median overall survival had not been reached for either group. Kaplan-Meier 24 month overall survival rates were 73.3% and 65.0%, respec-tively, trending in favor of KRd, but with a P value (.04) that did not meet the pre-specified stopping boundary for survival (P = .005).

“In this same population of patients – this is patients who have relapsed one, two or three times – the best result ever reported before with any combina-tion of chemotherapy was about 19 months, with a very similar cocktail of bortezomib, thalidomide and dexamethasone,” Dr. Stewart said at the briefing.

Neil Osterweil/Frontline Medical News

The KRd combination also appeared to be safe.

“Despite the fact that we added a third drug and patients were on treatment significantly longer, there was a fairly well balanced ratio of patients who had to discontinue treatment due to side effects. It’s important to note that cardiac and renal events which have been reported in some studies of heavily pre-treated patients [with carfilzomib] in the past, were marginally higher in the three-drug regimen, but overall were very consistent or even lower than had previously been reported [with single-agent carilzomib],” Dr. Stewart said.

Carfilzomib is an epoxyketone proteasome inhibitor that binds selectively to the constitutive proteasome and immunoproteasome. Unlike the first-in-class proteasome inhibitor, bortezomib (Velcade), carfilzomib irreversibly binds to and disables its targets, Dr. Stewart said in an interview.

In the ASPIRE (Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone for the Treatment of Patients with Relapsed Multiple Myeloma) trial, investigators enrolled 792 adults with relapsed multiple myeloma from 20 countries in North America, Europe, and the Middle East. The patients, who had previously received 1-3 prior lines of therapy, were randomly assigned to receive either KRd (carfilzomib 20 mg/m2 on days 1 and 2 of the first 28-day cycle, then 27 mg/m2 for days 8,9,15, and 16, and all days of subsequent cycles), oral lenolidamide 25 mg days 1-21, and oral dexamethasone days 1, 8, 15 and 22 of each cycle; or RD, which consisted of lenalidomide and dexamethasone in the same doses and on the same schedule as in KRd.

At the time of the data cutoff for the interim analysis in June 2014, 118 of 396 patients assigned to KRd were still on treatment, as were 86 of 396 in the RD group.

At the time of the analysis, 431 PFS events had been documented, and the study met its primary endpoint of superior PFS with the addition of carfilzomib.

Common adverse events, including diarrhea, cough, fever and hypertension were reported more frequently in the KRd group.

Remissions were more durable among patients who received carfilzomib, and these patients reported higher quality-of-life scores on the QLQ-C30 Global Health Status and Quality of Life scale, Dr. Stewart noted.

BOSTON – It’s time to test whether methotrexate is really up to snuff as a first-line therapy for psoriatic arthritis, Canadian investigators say.

They base that recommendation on findings from a retrospective study showing that fewer than 18% of patients with psoriatic arthritis treated with methotrexate achieved minimal disease activity (MDA) after 6 months.

They also found evidence to suggest that physicians may overestimate the benefits of methotrexate for psoriatic arthritis.

“Physician-dependent measures reveal good response to methotrexate at 6 months, but patient-reported measures are less responsive, possibly due to side effects, back pain, disease, [and/or] disability,” said Dr. Barry J. Sheane of the division of rheumatology in the department of medicine at the University of Toronto.

The data on the effects of methotrexate in psoriatic arthritis are considerably less impressive than are those seen with tumor necrosis factor–alpha inhibitors (TNFi), Dr. Sheane said. For example, at 24 weeks, 39% of patients treated with adalimumab (Humira) and 52% treated with infliximab (Remicade) had achieved MDA, he noted.

“We suggest that a randomized controlled trial of methotrexate compared to a TNF inhibitor is warranted,” Dr. Sheane said at the annual meeting of the American College of Rheumatology.

He and his colleagues reviewed records on 204 consecutive patients treated for psoriatic arthritis with methotrexate from January 2004 through April 2014. The patients, who had a mean duration of psoriatic arthritis of 6.2 years, were all naive to biological antirheumatic drugs and were initiating methotrexate therapy.

Of the 204 patients, 167 had data sufficient for a 6-month analysis.

The investigators defined MDA after 6 months on methotrexate, the primary endpoint, as the presence of at least five out of the following seven domains: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index (PASI) 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire (HAQ) score of 0.5 or less, patient global disease activity Visual Analog Scale score of 20 or lower, and patient pain Visual Analog Scale score of 15 or lower.

They found that 17.4% of patients (29 of 167) met the physician-rated criteria for MDA at 6 months, even though 82.6% of the patients (138) had a PASI score of 1 or lower, and 58.1% (97) had a swollen joint count of 1 or fewer.

When the patients were asked for their assessment of global disease activity, 13.2% (22) rated disease activity with a prespecified score of 20 or lower. Only 12% of patients (20) reported an HAQ score of 0.5 or less.

The mean methotrexate dose was similar between patients who achieved MDA (17.8 mg/week) and those who did not (17.3 mg/week). The median dose was 17.5 mg/week in each group.

After controlling for sex, baseline sacroiliitis, and duration of psoriasis and psoriatic arthritis at the start of methotrexate in a multivariate model, the authors found that only dactylitis, inflammatory back pain, and mechanical back pain were significantly associated with a lower probability of patients reaching MDA. The variables that did not prove to be associated with achieving MDA after 6 months on methotrexate included erythrocyte sedimentation rate, presence of nail disease, number of clinically damaged joints, and body mass index.

The study was internally funded. Dr. Sheane reported having no relevant disclosures.

BOSTON – It’s time to test whether methotrexate is really up to snuff as a first-line therapy for psoriatic arthritis, Canadian investigators say.

They base that recommendation on findings from a retrospective study showing that fewer than 18% of patients with psoriatic arthritis treated with methotrexate achieved minimal disease activity (MDA) after 6 months.

They also found evidence to suggest that physicians may overestimate the benefits of methotrexate for psoriatic arthritis.

“Physician-dependent measures reveal good response to methotrexate at 6 months, but patient-reported measures are less responsive, possibly due to side effects, back pain, disease, [and/or] disability,” said Dr. Barry J. Sheane of the division of rheumatology in the department of medicine at the University of Toronto.

The data on the effects of methotrexate in psoriatic arthritis are considerably less impressive than are those seen with tumor necrosis factor–alpha inhibitors (TNFi), Dr. Sheane said. For example, at 24 weeks, 39% of patients treated with adalimumab (Humira) and 52% treated with infliximab (Remicade) had achieved MDA, he noted.

“We suggest that a randomized controlled trial of methotrexate compared to a TNF inhibitor is warranted,” Dr. Sheane said at the annual meeting of the American College of Rheumatology.

He and his colleagues reviewed records on 204 consecutive patients treated for psoriatic arthritis with methotrexate from January 2004 through April 2014. The patients, who had a mean duration of psoriatic arthritis of 6.2 years, were all naive to biological antirheumatic drugs and were initiating methotrexate therapy.

Of the 204 patients, 167 had data sufficient for a 6-month analysis.

The investigators defined MDA after 6 months on methotrexate, the primary endpoint, as the presence of at least five out of the following seven domains: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index (PASI) 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire (HAQ) score of 0.5 or less, patient global disease activity Visual Analog Scale score of 20 or lower, and patient pain Visual Analog Scale score of 15 or lower.

They found that 17.4% of patients (29 of 167) met the physician-rated criteria for MDA at 6 months, even though 82.6% of the patients (138) had a PASI score of 1 or lower, and 58.1% (97) had a swollen joint count of 1 or fewer.

When the patients were asked for their assessment of global disease activity, 13.2% (22) rated disease activity with a prespecified score of 20 or lower. Only 12% of patients (20) reported an HAQ score of 0.5 or less.

The mean methotrexate dose was similar between patients who achieved MDA (17.8 mg/week) and those who did not (17.3 mg/week). The median dose was 17.5 mg/week in each group.

After controlling for sex, baseline sacroiliitis, and duration of psoriasis and psoriatic arthritis at the start of methotrexate in a multivariate model, the authors found that only dactylitis, inflammatory back pain, and mechanical back pain were significantly associated with a lower probability of patients reaching MDA. The variables that did not prove to be associated with achieving MDA after 6 months on methotrexate included erythrocyte sedimentation rate, presence of nail disease, number of clinically damaged joints, and body mass index.

The study was internally funded. Dr. Sheane reported having no relevant disclosures.

BOSTON – It’s time to test whether methotrexate is really up to snuff as a first-line therapy for psoriatic arthritis, Canadian investigators say.

They base that recommendation on findings from a retrospective study showing that fewer than 18% of patients with psoriatic arthritis treated with methotrexate achieved minimal disease activity (MDA) after 6 months.

They also found evidence to suggest that physicians may overestimate the benefits of methotrexate for psoriatic arthritis.

“Physician-dependent measures reveal good response to methotrexate at 6 months, but patient-reported measures are less responsive, possibly due to side effects, back pain, disease, [and/or] disability,” said Dr. Barry J. Sheane of the division of rheumatology in the department of medicine at the University of Toronto.

The data on the effects of methotrexate in psoriatic arthritis are considerably less impressive than are those seen with tumor necrosis factor–alpha inhibitors (TNFi), Dr. Sheane said. For example, at 24 weeks, 39% of patients treated with adalimumab (Humira) and 52% treated with infliximab (Remicade) had achieved MDA, he noted.

“We suggest that a randomized controlled trial of methotrexate compared to a TNF inhibitor is warranted,” Dr. Sheane said at the annual meeting of the American College of Rheumatology.

He and his colleagues reviewed records on 204 consecutive patients treated for psoriatic arthritis with methotrexate from January 2004 through April 2014. The patients, who had a mean duration of psoriatic arthritis of 6.2 years, were all naive to biological antirheumatic drugs and were initiating methotrexate therapy.

Of the 204 patients, 167 had data sufficient for a 6-month analysis.

The investigators defined MDA after 6 months on methotrexate, the primary endpoint, as the presence of at least five out of the following seven domains: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index (PASI) 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire (HAQ) score of 0.5 or less, patient global disease activity Visual Analog Scale score of 20 or lower, and patient pain Visual Analog Scale score of 15 or lower.

They found that 17.4% of patients (29 of 167) met the physician-rated criteria for MDA at 6 months, even though 82.6% of the patients (138) had a PASI score of 1 or lower, and 58.1% (97) had a swollen joint count of 1 or fewer.

When the patients were asked for their assessment of global disease activity, 13.2% (22) rated disease activity with a prespecified score of 20 or lower. Only 12% of patients (20) reported an HAQ score of 0.5 or less.

The mean methotrexate dose was similar between patients who achieved MDA (17.8 mg/week) and those who did not (17.3 mg/week). The median dose was 17.5 mg/week in each group.

After controlling for sex, baseline sacroiliitis, and duration of psoriasis and psoriatic arthritis at the start of methotrexate in a multivariate model, the authors found that only dactylitis, inflammatory back pain, and mechanical back pain were significantly associated with a lower probability of patients reaching MDA. The variables that did not prove to be associated with achieving MDA after 6 months on methotrexate included erythrocyte sedimentation rate, presence of nail disease, number of clinically damaged joints, and body mass index.

The study was internally funded. Dr. Sheane reported having no relevant disclosures.

BOSTON – Tapering but perhaps not completely stopping tumor necrosis factor inhibitors can result in good control of rheumatoid arthritis with considerable cost savings, according to investigators in two studies.

Dr. Noortje van Herwaarden and colleagues from Sint Maartenskliniek in Nijmegen, the Netherlands, conducted a randomized, open-label study of dose-reduction vs. usual care in 180 patients with stable, well-controlled rheumatoid arthritis (RA) on a tumor necrosis factor inhibitor (TNFi) – either adalimumab (Humira) or etanercept (Enbrel) – plus in some cases a stable disease-modifying antirheumatic drug (DMARD) or glucocorticoid.

Neil Osterweil/Frontline Medical News

“This is the first study to demonstrate that disease activity–guided tapering of adalimumab and etanercept in RA patients doing well is noninferior to usual care regarding major flare,” Dr. van Herwaarden said at the annual meeting of the American College of Rheumatology.

She and her colleagues randomly assigned the patients on a 2:1 basis to TNFi dose reduction or usual care. Dose reduction was accomplished with a stepwise increase in the interval between injections every 3 months until flare. Flare was defined as an increase greater than 1.2 in the 28-joint Disease Activity Score calculated using C-reactive protein (DAS28-CRP) or a DAS28-CRP increase greater than 0.6 with a current DAS28-CRP score of 3.2 or greater, compared with baseline. Follow-up was for 18 months with visits every 3 months or any time a patient reported more symptoms.

Among 169 patients available for a per-protocol analysis, the cumulative incidence of major DAS28-CRP flares lasting more than 3 months (the primary endpoint) was 12% in patients randomized to dose reduction, compared with 10% in the usual-care group, a difference that was not statistically significant. The absolute difference was 2% and the 95% confidence interval of –12% to 12% fell below the prespecified margin of 20% for noninferiority of dose reduction, Dr. van Herwaarden said.

However, there was a significant difference in the cumulative incidence of short-term flares lasting 3 months or less, which occurred in 73% of patients on dose reduction, compared with 27% of those on usual care (P < .001).

Measures of disease activity, functioning, and quality of life were generally similar throughout the study, the investigators found.

In the dose-reduction group, 43% of patients successfully tapered the TNFi, and 20% stopped altogether, but for the remaining 37% of patients, no dose reduction was possible. There were no between-group differences in the use of DMARDs or glucocorticoids.

Minor radiographic progression

Looking at radiographic progression, the investigators found no differences in minimal clinically important change or smallest detectable change between the dose-reduction and usual-care groups. But significantly more patients in the dose-reduction group met stricter cutoff for progression of 0.5%, compared with the usual care group (32 patients vs. 15 patients, respectively). The total modified Sharp-van der Heijde score and joint-space narrowing scores also favored usual care, but the erosion score was not different between the groups.

Adverse events were similar between the groups, but there were more serious adverse events in the dose-reduction group, most of which were attributable to planned surgery among these patients, Dr. van Herwaarden said.

Mean total per-patient costs for the 18-month follow-up were almost $11,000 lower in the dose-reduction group ($15,728 vs. $26,576). The decremental cost-effectiveness ratio was calculated to be $488,116 – the amount that is saved when 1 quality-adjusted life-year (QALY) is lost. The difference is about five times higher than the widely accepted amount that society is willing to pay for 1 QALY gained, Dr. van Herwaarden said.

Reduce yes, stop no

In a separate study, Japanese researchers found that stopping a biological agent altogether in patients with RA in remission was associated with a high rate of failure.

Neil Osterweil/Frontline Medical News

The investigators looked at a Japanese rheumatic diseases registry data and found that among 31 patients who discontinued biological DMARDs while in remission in typical clinical practice, 71% by 1 year and 76% by 2 years had a treatment failure, defined as restart of the biological agent, glucocorticoid dose escalation, nonbiological DMARD addition, or loss of remission on the clinical disease activity index.

“Maintenance of disease activity after discontinuation is relatively difficult in established RA patients in the typical clinical practice setting. This may suggest that a reduction in dose intensity – either by prolongation of treatment intervals or by dose induction intervals – may be a more feasible option in established RA patients,” said Dr. Kazuki Yoshida, currently a research fellow in the section of clinical sciences in the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital in Boston.

Dr. van Herwaarden’s study was internally funded. Dr. Yoshida’s study was supported by a grant to Kameda Medical Center, Kamogawa City, Japan. Both physicians reported having no relevant disclosures.

BOSTON – Tapering but perhaps not completely stopping tumor necrosis factor inhibitors can result in good control of rheumatoid arthritis with considerable cost savings, according to investigators in two studies.

Dr. Noortje van Herwaarden and colleagues from Sint Maartenskliniek in Nijmegen, the Netherlands, conducted a randomized, open-label study of dose-reduction vs. usual care in 180 patients with stable, well-controlled rheumatoid arthritis (RA) on a tumor necrosis factor inhibitor (TNFi) – either adalimumab (Humira) or etanercept (Enbrel) – plus in some cases a stable disease-modifying antirheumatic drug (DMARD) or glucocorticoid.

Neil Osterweil/Frontline Medical News

“This is the first study to demonstrate that disease activity–guided tapering of adalimumab and etanercept in RA patients doing well is noninferior to usual care regarding major flare,” Dr. van Herwaarden said at the annual meeting of the American College of Rheumatology.

She and her colleagues randomly assigned the patients on a 2:1 basis to TNFi dose reduction or usual care. Dose reduction was accomplished with a stepwise increase in the interval between injections every 3 months until flare. Flare was defined as an increase greater than 1.2 in the 28-joint Disease Activity Score calculated using C-reactive protein (DAS28-CRP) or a DAS28-CRP increase greater than 0.6 with a current DAS28-CRP score of 3.2 or greater, compared with baseline. Follow-up was for 18 months with visits every 3 months or any time a patient reported more symptoms.

Among 169 patients available for a per-protocol analysis, the cumulative incidence of major DAS28-CRP flares lasting more than 3 months (the primary endpoint) was 12% in patients randomized to dose reduction, compared with 10% in the usual-care group, a difference that was not statistically significant. The absolute difference was 2% and the 95% confidence interval of –12% to 12% fell below the prespecified margin of 20% for noninferiority of dose reduction, Dr. van Herwaarden said.

However, there was a significant difference in the cumulative incidence of short-term flares lasting 3 months or less, which occurred in 73% of patients on dose reduction, compared with 27% of those on usual care (P < .001).

Measures of disease activity, functioning, and quality of life were generally similar throughout the study, the investigators found.

In the dose-reduction group, 43% of patients successfully tapered the TNFi, and 20% stopped altogether, but for the remaining 37% of patients, no dose reduction was possible. There were no between-group differences in the use of DMARDs or glucocorticoids.

Minor radiographic progression

Looking at radiographic progression, the investigators found no differences in minimal clinically important change or smallest detectable change between the dose-reduction and usual-care groups. But significantly more patients in the dose-reduction group met stricter cutoff for progression of 0.5%, compared with the usual care group (32 patients vs. 15 patients, respectively). The total modified Sharp-van der Heijde score and joint-space narrowing scores also favored usual care, but the erosion score was not different between the groups.

Adverse events were similar between the groups, but there were more serious adverse events in the dose-reduction group, most of which were attributable to planned surgery among these patients, Dr. van Herwaarden said.

Mean total per-patient costs for the 18-month follow-up were almost $11,000 lower in the dose-reduction group ($15,728 vs. $26,576). The decremental cost-effectiveness ratio was calculated to be $488,116 – the amount that is saved when 1 quality-adjusted life-year (QALY) is lost. The difference is about five times higher than the widely accepted amount that society is willing to pay for 1 QALY gained, Dr. van Herwaarden said.

Reduce yes, stop no

In a separate study, Japanese researchers found that stopping a biological agent altogether in patients with RA in remission was associated with a high rate of failure.

Neil Osterweil/Frontline Medical News

The investigators looked at a Japanese rheumatic diseases registry data and found that among 31 patients who discontinued biological DMARDs while in remission in typical clinical practice, 71% by 1 year and 76% by 2 years had a treatment failure, defined as restart of the biological agent, glucocorticoid dose escalation, nonbiological DMARD addition, or loss of remission on the clinical disease activity index.

“Maintenance of disease activity after discontinuation is relatively difficult in established RA patients in the typical clinical practice setting. This may suggest that a reduction in dose intensity – either by prolongation of treatment intervals or by dose induction intervals – may be a more feasible option in established RA patients,” said Dr. Kazuki Yoshida, currently a research fellow in the section of clinical sciences in the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital in Boston.

Dr. van Herwaarden’s study was internally funded. Dr. Yoshida’s study was supported by a grant to Kameda Medical Center, Kamogawa City, Japan. Both physicians reported having no relevant disclosures.

BOSTON – Tapering but perhaps not completely stopping tumor necrosis factor inhibitors can result in good control of rheumatoid arthritis with considerable cost savings, according to investigators in two studies.

Dr. Noortje van Herwaarden and colleagues from Sint Maartenskliniek in Nijmegen, the Netherlands, conducted a randomized, open-label study of dose-reduction vs. usual care in 180 patients with stable, well-controlled rheumatoid arthritis (RA) on a tumor necrosis factor inhibitor (TNFi) – either adalimumab (Humira) or etanercept (Enbrel) – plus in some cases a stable disease-modifying antirheumatic drug (DMARD) or glucocorticoid.

Neil Osterweil/Frontline Medical News

“This is the first study to demonstrate that disease activity–guided tapering of adalimumab and etanercept in RA patients doing well is noninferior to usual care regarding major flare,” Dr. van Herwaarden said at the annual meeting of the American College of Rheumatology.

She and her colleagues randomly assigned the patients on a 2:1 basis to TNFi dose reduction or usual care. Dose reduction was accomplished with a stepwise increase in the interval between injections every 3 months until flare. Flare was defined as an increase greater than 1.2 in the 28-joint Disease Activity Score calculated using C-reactive protein (DAS28-CRP) or a DAS28-CRP increase greater than 0.6 with a current DAS28-CRP score of 3.2 or greater, compared with baseline. Follow-up was for 18 months with visits every 3 months or any time a patient reported more symptoms.

Among 169 patients available for a per-protocol analysis, the cumulative incidence of major DAS28-CRP flares lasting more than 3 months (the primary endpoint) was 12% in patients randomized to dose reduction, compared with 10% in the usual-care group, a difference that was not statistically significant. The absolute difference was 2% and the 95% confidence interval of –12% to 12% fell below the prespecified margin of 20% for noninferiority of dose reduction, Dr. van Herwaarden said.

However, there was a significant difference in the cumulative incidence of short-term flares lasting 3 months or less, which occurred in 73% of patients on dose reduction, compared with 27% of those on usual care (P < .001).

Measures of disease activity, functioning, and quality of life were generally similar throughout the study, the investigators found.

In the dose-reduction group, 43% of patients successfully tapered the TNFi, and 20% stopped altogether, but for the remaining 37% of patients, no dose reduction was possible. There were no between-group differences in the use of DMARDs or glucocorticoids.

Minor radiographic progression

Looking at radiographic progression, the investigators found no differences in minimal clinically important change or smallest detectable change between the dose-reduction and usual-care groups. But significantly more patients in the dose-reduction group met stricter cutoff for progression of 0.5%, compared with the usual care group (32 patients vs. 15 patients, respectively). The total modified Sharp-van der Heijde score and joint-space narrowing scores also favored usual care, but the erosion score was not different between the groups.

Adverse events were similar between the groups, but there were more serious adverse events in the dose-reduction group, most of which were attributable to planned surgery among these patients, Dr. van Herwaarden said.

Mean total per-patient costs for the 18-month follow-up were almost $11,000 lower in the dose-reduction group ($15,728 vs. $26,576). The decremental cost-effectiveness ratio was calculated to be $488,116 – the amount that is saved when 1 quality-adjusted life-year (QALY) is lost. The difference is about five times higher than the widely accepted amount that society is willing to pay for 1 QALY gained, Dr. van Herwaarden said.

Reduce yes, stop no

In a separate study, Japanese researchers found that stopping a biological agent altogether in patients with RA in remission was associated with a high rate of failure.

Neil Osterweil/Frontline Medical News

The investigators looked at a Japanese rheumatic diseases registry data and found that among 31 patients who discontinued biological DMARDs while in remission in typical clinical practice, 71% by 1 year and 76% by 2 years had a treatment failure, defined as restart of the biological agent, glucocorticoid dose escalation, nonbiological DMARD addition, or loss of remission on the clinical disease activity index.

“Maintenance of disease activity after discontinuation is relatively difficult in established RA patients in the typical clinical practice setting. This may suggest that a reduction in dose intensity – either by prolongation of treatment intervals or by dose induction intervals – may be a more feasible option in established RA patients,” said Dr. Kazuki Yoshida, currently a research fellow in the section of clinical sciences in the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital in Boston.

Dr. van Herwaarden’s study was internally funded. Dr. Yoshida’s study was supported by a grant to Kameda Medical Center, Kamogawa City, Japan. Both physicians reported having no relevant disclosures.