ACR Annual Meeting 2014

BOSTON – Secukinumab improved quality of life and symptoms in patients with psoriatic arthritis, regardless of whether they had received prior anti-tumor-necrosis factor therapy or were concurrently receiving methotrexate, Dr. Ian B. McInnes reported at the annual meeting of the American College of Rheumatology.

A 300-mg dose of the investigational drug, which is given subcutaneously, proved to be the most effective dose, Dr. McInnes, of the University of Glasgow, Scotland, said in his presentation of the 24-week results of the FUTURE 2 study. The primary endpoint, a response of at least ACR20, was achieved by 54% of 100 patients given the 300-mg dose and by 51% of 100 patients given the 150-mg dose. The 75-mg dose was far less effective, with a 29% response in 99 patients; the 98 patients given placebo had a 15% response.

At the 150-mg and 300-mg doses, the rates of ACR20 responses were comparable whether or not patients were also taking concomitant methotrexate. Further, the drug’s safety profile was comparable to placebo, Dr. McInnes said.

Mary Jo Dales/Frontline Medical News

An ACR50 was achieved by 35% of patients given secukinumab at either 300 mg or 150 mg, and by 18% of those given 75 mg and 7% of those given placebo. About 20% of patients given the higher doses had an ACR70 response, as did 6% of those given 75 mg and 1% of those given placebo.

At the 300-mg dose, secukinumab also resolved dactylitis and enthesitis in approximately half of the affected patients.

Mean improvements in quality of life based on patients’ SF 36 PCS score (Short Form-36 Physical Component Summary) at 24 weeks from baseline were 7.25 in those on the 300-mg dose and 6.39 in those on the 150-mg dose. Those on the 75-mg dose had a 4.38-point mean improvement, whereas patients on placebo had a 1.34-point mean improvement in SF 36 PCS.

No safety signals were noted; adverse events were few and comparable to placebo. Five subjects on the active drug had mild to moderate candidal infections that responded to oral therapy. Neutropenia occurred in one patient in the 300-mg dose group and in one patient in the placebo group, but was transient and patients continued on therapy.

Secukinumab is a fully-human IgG1k monoclonal antibody that selectively targets IL-17A. The drug, manufactured by Novartis, was unanimously recommended for approval by an advisory committee to the Food and Drug Administration. It was administered weekly as a subcutaneous injection for the first 4 weeks of the study, then given again at week 8 and once every 4 weeks thereafter in patients assigned to one of the secukinumab arms of the double-blind, randomized study. Patient assigned to the placebo group were either responders and assigned to receive secukinumab at week 24 and every 4 weeks thereafter or were nonresponders assigned to receive secukinumab at week 16 and every 4 weeks thereafter. Only patients with at least 20% reductions in the number of tender joints or swollen joints continue to receive the drug beyond 1 year.

To be eligible for the study, patients needed to have a diagnosis of active psoriatic arthritis classified by CASPAR criteria and tenderness in at least 3 of 78 joints and swelling of at least 3 of 76 joints. They additionally needed to have an inadequate response to nonsteroidal anti-inflammatory drugs, methotrexate, or anti-TNF therapy

The primary endpoint of the study was ACR20 response at 24 weeks. Secondary endpoints included PASI 75 and PASI 90 responses, change in DAS28-CRP (28-joint Disease Activity Score using C-reactive protein) from baseline, change in SF-36 PCS and HAQ-DI (Health Assessment Questionnaire-Disability Index) from baseline, ACR50 response, the proportion of subjects with dactylitis and enthesitis, and overall safety and tolerability.

As of press time, the FDA was expected to take additional action in January 2015, according to Novartis.

The study was sponsored by Novartis, the maker of secukinumab. Dr. McInnes receives consulting fees from Novartis as well as multiple other pharmaceutical companies.

mdales@frontlinemedcom.com

BOSTON – Secukinumab improved quality of life and symptoms in patients with psoriatic arthritis, regardless of whether they had received prior anti-tumor-necrosis factor therapy or were concurrently receiving methotrexate, Dr. Ian B. McInnes reported at the annual meeting of the American College of Rheumatology.

A 300-mg dose of the investigational drug, which is given subcutaneously, proved to be the most effective dose, Dr. McInnes, of the University of Glasgow, Scotland, said in his presentation of the 24-week results of the FUTURE 2 study. The primary endpoint, a response of at least ACR20, was achieved by 54% of 100 patients given the 300-mg dose and by 51% of 100 patients given the 150-mg dose. The 75-mg dose was far less effective, with a 29% response in 99 patients; the 98 patients given placebo had a 15% response.

At the 150-mg and 300-mg doses, the rates of ACR20 responses were comparable whether or not patients were also taking concomitant methotrexate. Further, the drug’s safety profile was comparable to placebo, Dr. McInnes said.

Mary Jo Dales/Frontline Medical News

An ACR50 was achieved by 35% of patients given secukinumab at either 300 mg or 150 mg, and by 18% of those given 75 mg and 7% of those given placebo. About 20% of patients given the higher doses had an ACR70 response, as did 6% of those given 75 mg and 1% of those given placebo.

At the 300-mg dose, secukinumab also resolved dactylitis and enthesitis in approximately half of the affected patients.

Mean improvements in quality of life based on patients’ SF 36 PCS score (Short Form-36 Physical Component Summary) at 24 weeks from baseline were 7.25 in those on the 300-mg dose and 6.39 in those on the 150-mg dose. Those on the 75-mg dose had a 4.38-point mean improvement, whereas patients on placebo had a 1.34-point mean improvement in SF 36 PCS.

No safety signals were noted; adverse events were few and comparable to placebo. Five subjects on the active drug had mild to moderate candidal infections that responded to oral therapy. Neutropenia occurred in one patient in the 300-mg dose group and in one patient in the placebo group, but was transient and patients continued on therapy.

Secukinumab is a fully-human IgG1k monoclonal antibody that selectively targets IL-17A. The drug, manufactured by Novartis, was unanimously recommended for approval by an advisory committee to the Food and Drug Administration. It was administered weekly as a subcutaneous injection for the first 4 weeks of the study, then given again at week 8 and once every 4 weeks thereafter in patients assigned to one of the secukinumab arms of the double-blind, randomized study. Patient assigned to the placebo group were either responders and assigned to receive secukinumab at week 24 and every 4 weeks thereafter or were nonresponders assigned to receive secukinumab at week 16 and every 4 weeks thereafter. Only patients with at least 20% reductions in the number of tender joints or swollen joints continue to receive the drug beyond 1 year.

To be eligible for the study, patients needed to have a diagnosis of active psoriatic arthritis classified by CASPAR criteria and tenderness in at least 3 of 78 joints and swelling of at least 3 of 76 joints. They additionally needed to have an inadequate response to nonsteroidal anti-inflammatory drugs, methotrexate, or anti-TNF therapy

The primary endpoint of the study was ACR20 response at 24 weeks. Secondary endpoints included PASI 75 and PASI 90 responses, change in DAS28-CRP (28-joint Disease Activity Score using C-reactive protein) from baseline, change in SF-36 PCS and HAQ-DI (Health Assessment Questionnaire-Disability Index) from baseline, ACR50 response, the proportion of subjects with dactylitis and enthesitis, and overall safety and tolerability.

As of press time, the FDA was expected to take additional action in January 2015, according to Novartis.

The study was sponsored by Novartis, the maker of secukinumab. Dr. McInnes receives consulting fees from Novartis as well as multiple other pharmaceutical companies.

mdales@frontlinemedcom.com

BOSTON – Secukinumab improved quality of life and symptoms in patients with psoriatic arthritis, regardless of whether they had received prior anti-tumor-necrosis factor therapy or were concurrently receiving methotrexate, Dr. Ian B. McInnes reported at the annual meeting of the American College of Rheumatology.

A 300-mg dose of the investigational drug, which is given subcutaneously, proved to be the most effective dose, Dr. McInnes, of the University of Glasgow, Scotland, said in his presentation of the 24-week results of the FUTURE 2 study. The primary endpoint, a response of at least ACR20, was achieved by 54% of 100 patients given the 300-mg dose and by 51% of 100 patients given the 150-mg dose. The 75-mg dose was far less effective, with a 29% response in 99 patients; the 98 patients given placebo had a 15% response.

At the 150-mg and 300-mg doses, the rates of ACR20 responses were comparable whether or not patients were also taking concomitant methotrexate. Further, the drug’s safety profile was comparable to placebo, Dr. McInnes said.

Mary Jo Dales/Frontline Medical News

An ACR50 was achieved by 35% of patients given secukinumab at either 300 mg or 150 mg, and by 18% of those given 75 mg and 7% of those given placebo. About 20% of patients given the higher doses had an ACR70 response, as did 6% of those given 75 mg and 1% of those given placebo.

At the 300-mg dose, secukinumab also resolved dactylitis and enthesitis in approximately half of the affected patients.

Mean improvements in quality of life based on patients’ SF 36 PCS score (Short Form-36 Physical Component Summary) at 24 weeks from baseline were 7.25 in those on the 300-mg dose and 6.39 in those on the 150-mg dose. Those on the 75-mg dose had a 4.38-point mean improvement, whereas patients on placebo had a 1.34-point mean improvement in SF 36 PCS.

No safety signals were noted; adverse events were few and comparable to placebo. Five subjects on the active drug had mild to moderate candidal infections that responded to oral therapy. Neutropenia occurred in one patient in the 300-mg dose group and in one patient in the placebo group, but was transient and patients continued on therapy.

Secukinumab is a fully-human IgG1k monoclonal antibody that selectively targets IL-17A. The drug, manufactured by Novartis, was unanimously recommended for approval by an advisory committee to the Food and Drug Administration. It was administered weekly as a subcutaneous injection for the first 4 weeks of the study, then given again at week 8 and once every 4 weeks thereafter in patients assigned to one of the secukinumab arms of the double-blind, randomized study. Patient assigned to the placebo group were either responders and assigned to receive secukinumab at week 24 and every 4 weeks thereafter or were nonresponders assigned to receive secukinumab at week 16 and every 4 weeks thereafter. Only patients with at least 20% reductions in the number of tender joints or swollen joints continue to receive the drug beyond 1 year.

To be eligible for the study, patients needed to have a diagnosis of active psoriatic arthritis classified by CASPAR criteria and tenderness in at least 3 of 78 joints and swelling of at least 3 of 76 joints. They additionally needed to have an inadequate response to nonsteroidal anti-inflammatory drugs, methotrexate, or anti-TNF therapy

The primary endpoint of the study was ACR20 response at 24 weeks. Secondary endpoints included PASI 75 and PASI 90 responses, change in DAS28-CRP (28-joint Disease Activity Score using C-reactive protein) from baseline, change in SF-36 PCS and HAQ-DI (Health Assessment Questionnaire-Disability Index) from baseline, ACR50 response, the proportion of subjects with dactylitis and enthesitis, and overall safety and tolerability.

As of press time, the FDA was expected to take additional action in January 2015, according to Novartis.

The study was sponsored by Novartis, the maker of secukinumab. Dr. McInnes receives consulting fees from Novartis as well as multiple other pharmaceutical companies.

mdales@frontlinemedcom.com

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.

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.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – Golimumab was significantly better than placebo at reducing disease activity and inflammation in patients with nonradiographic axial spondyloarthritis, but only among those who were positive for disease on MRI or the inflammation marker C-reactive protein.

In the randomized, double-blind, placebo-controlled GO-AHEAD trial of 198 patients with nonradiographic axial spondyloarthritis (nr-axSpA), 71.1% of patients treated with golimumab (Simponi) achieved the primary endpoint of an ASAS 20 at week 16, compared with 40% of patients on placebo (P < .0001), reported Dr. Joachim Sieper of Charité Medical University in Berlin.

But in a subgroup analysis of patients with normal MRI and C-reactive protein (CRP) levels at baseline, there was no significant difference in ASAS 20 responses at week 16, although the number of patients may have been too small to reveal an effect, Dr. Sieper said.

“There was no difference regarding any adverse event, no difference regarding serious adverse events, and also no difference regarding other adverse events, and there were no deaths in this study,” he said at the annual meeting of the American College of Rheumatology.

Golimumab is a tumor necrosis factor–alpha (TNF-alpha) inhibitor approved in the United States for treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe ulcerative colitis.

The phase III trial was a double-blind, placebo-controlled study in 198 patients with a diagnosis of active axSpA according to Assessment of Spondyloarthritis (ASAS) criteria, a disease duration of less than 5 years since symptom onset, and chronic back pain lasting for at least 3 months.

The patients were randomly assigned to receive either golimumab 50 mg every 4 weeks or placebo via subcutaneous injection. A total of 93 patients assigned to golimumab and 97 assigned to placebo completed 16 weeks of therapy.

The primary endpoint was the percentage of patients achieving an ASAS 20, defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100 scale in three of four domains:

• Patient global assessment (by VAS [visual analog scale] global assessment).

• Pain assessment (the average of VAS total and nocturnal pain scores).

• Function (represented by BASFI [Bath Ankylosing Spondylitis Functional Index]).

• Inflammation (the average score of the last two VASs in the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], concerning morning stiffness intensity and duration), as well as an absence of deterioration (20% or greater worsening) in the potential remaining domain.

As noted before, golimumab met the primary endpoint among all patients, but in a subanalysis the TNF-alpha inhibitor was significantly better than placebo only among patients with evidence of inflammation on MRI or an elevated CRP at baseline (76.9% vs. 37.5%; P < .0001).

Golimumab was also superior to placebo at week 16 on three secondary endpoints: BASDAI 50 (57.7% vs. 30%; P < .0001), ASAS partial remission (33% vs. 18%; P = .0136), and mean change in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score (–5.3 vs. –0.9; P < .0001).

In an intention-to-treat analysis, more patients on placebo had any adverse events after 60 weeks of follow-up (41.2% for golimumab vs. 47% for placebo). Patients on placebo were also more likely to have an event judged by the investigator to be related to the assigned medication (13.4% vs. 17%). There were no serious infections, opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or deaths.

The study was sponsored by Merck Sharp & Dohme. Dr. Sieper disclosed receiving honoraria, speaker fees, and/or consultancy payments from the company. Four of the study coauthors are employees of Merck.

BOSTON – Golimumab was significantly better than placebo at reducing disease activity and inflammation in patients with nonradiographic axial spondyloarthritis, but only among those who were positive for disease on MRI or the inflammation marker C-reactive protein.

In the randomized, double-blind, placebo-controlled GO-AHEAD trial of 198 patients with nonradiographic axial spondyloarthritis (nr-axSpA), 71.1% of patients treated with golimumab (Simponi) achieved the primary endpoint of an ASAS 20 at week 16, compared with 40% of patients on placebo (P < .0001), reported Dr. Joachim Sieper of Charité Medical University in Berlin.

But in a subgroup analysis of patients with normal MRI and C-reactive protein (CRP) levels at baseline, there was no significant difference in ASAS 20 responses at week 16, although the number of patients may have been too small to reveal an effect, Dr. Sieper said.

“There was no difference regarding any adverse event, no difference regarding serious adverse events, and also no difference regarding other adverse events, and there were no deaths in this study,” he said at the annual meeting of the American College of Rheumatology.

Golimumab is a tumor necrosis factor–alpha (TNF-alpha) inhibitor approved in the United States for treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe ulcerative colitis.

The phase III trial was a double-blind, placebo-controlled study in 198 patients with a diagnosis of active axSpA according to Assessment of Spondyloarthritis (ASAS) criteria, a disease duration of less than 5 years since symptom onset, and chronic back pain lasting for at least 3 months.

The patients were randomly assigned to receive either golimumab 50 mg every 4 weeks or placebo via subcutaneous injection. A total of 93 patients assigned to golimumab and 97 assigned to placebo completed 16 weeks of therapy.

The primary endpoint was the percentage of patients achieving an ASAS 20, defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100 scale in three of four domains:

• Patient global assessment (by VAS [visual analog scale] global assessment).

• Pain assessment (the average of VAS total and nocturnal pain scores).

• Function (represented by BASFI [Bath Ankylosing Spondylitis Functional Index]).

• Inflammation (the average score of the last two VASs in the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], concerning morning stiffness intensity and duration), as well as an absence of deterioration (20% or greater worsening) in the potential remaining domain.

As noted before, golimumab met the primary endpoint among all patients, but in a subanalysis the TNF-alpha inhibitor was significantly better than placebo only among patients with evidence of inflammation on MRI or an elevated CRP at baseline (76.9% vs. 37.5%; P < .0001).

Golimumab was also superior to placebo at week 16 on three secondary endpoints: BASDAI 50 (57.7% vs. 30%; P < .0001), ASAS partial remission (33% vs. 18%; P = .0136), and mean change in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score (–5.3 vs. –0.9; P < .0001).

In an intention-to-treat analysis, more patients on placebo had any adverse events after 60 weeks of follow-up (41.2% for golimumab vs. 47% for placebo). Patients on placebo were also more likely to have an event judged by the investigator to be related to the assigned medication (13.4% vs. 17%). There were no serious infections, opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or deaths.

The study was sponsored by Merck Sharp & Dohme. Dr. Sieper disclosed receiving honoraria, speaker fees, and/or consultancy payments from the company. Four of the study coauthors are employees of Merck.

BOSTON – Golimumab was significantly better than placebo at reducing disease activity and inflammation in patients with nonradiographic axial spondyloarthritis, but only among those who were positive for disease on MRI or the inflammation marker C-reactive protein.

In the randomized, double-blind, placebo-controlled GO-AHEAD trial of 198 patients with nonradiographic axial spondyloarthritis (nr-axSpA), 71.1% of patients treated with golimumab (Simponi) achieved the primary endpoint of an ASAS 20 at week 16, compared with 40% of patients on placebo (P < .0001), reported Dr. Joachim Sieper of Charité Medical University in Berlin.

But in a subgroup analysis of patients with normal MRI and C-reactive protein (CRP) levels at baseline, there was no significant difference in ASAS 20 responses at week 16, although the number of patients may have been too small to reveal an effect, Dr. Sieper said.

“There was no difference regarding any adverse event, no difference regarding serious adverse events, and also no difference regarding other adverse events, and there were no deaths in this study,” he said at the annual meeting of the American College of Rheumatology.

Golimumab is a tumor necrosis factor–alpha (TNF-alpha) inhibitor approved in the United States for treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe ulcerative colitis.

The phase III trial was a double-blind, placebo-controlled study in 198 patients with a diagnosis of active axSpA according to Assessment of Spondyloarthritis (ASAS) criteria, a disease duration of less than 5 years since symptom onset, and chronic back pain lasting for at least 3 months.

The patients were randomly assigned to receive either golimumab 50 mg every 4 weeks or placebo via subcutaneous injection. A total of 93 patients assigned to golimumab and 97 assigned to placebo completed 16 weeks of therapy.

The primary endpoint was the percentage of patients achieving an ASAS 20, defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100 scale in three of four domains:

• Patient global assessment (by VAS [visual analog scale] global assessment).

• Pain assessment (the average of VAS total and nocturnal pain scores).

• Function (represented by BASFI [Bath Ankylosing Spondylitis Functional Index]).

• Inflammation (the average score of the last two VASs in the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], concerning morning stiffness intensity and duration), as well as an absence of deterioration (20% or greater worsening) in the potential remaining domain.

As noted before, golimumab met the primary endpoint among all patients, but in a subanalysis the TNF-alpha inhibitor was significantly better than placebo only among patients with evidence of inflammation on MRI or an elevated CRP at baseline (76.9% vs. 37.5%; P < .0001).

Golimumab was also superior to placebo at week 16 on three secondary endpoints: BASDAI 50 (57.7% vs. 30%; P < .0001), ASAS partial remission (33% vs. 18%; P = .0136), and mean change in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score (–5.3 vs. –0.9; P < .0001).

In an intention-to-treat analysis, more patients on placebo had any adverse events after 60 weeks of follow-up (41.2% for golimumab vs. 47% for placebo). Patients on placebo were also more likely to have an event judged by the investigator to be related to the assigned medication (13.4% vs. 17%). There were no serious infections, opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or deaths.

The study was sponsored by Merck Sharp & Dohme. Dr. Sieper disclosed receiving honoraria, speaker fees, and/or consultancy payments from the company. Four of the study coauthors are employees of Merck.

BOSTON– In the search for safer alternatives to glucocorticoid therapy, DAGR (PF-0417327) may prove to be a contender. The investigational drug is a selective, high-affinity, dissociated agonist of the glucocorticoid receptor, and appeared to be associated with fewer potential adverse events than are typically seen with glucocorticoids in a phase II trial that compared 8 weeks of the drug against placebo and prednisone.

The findings suggest that DAGR is therapeutically equivalent to prednisone 10 mg once daily, but with side effects comparable with those seen with prednisone 5 mg once daily and with no clinical symptoms of adrenal insufficiency. Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant in Portola Valley, Calif., presented data on the drug during the late-breaker session and discussed the implications of the findings at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON– In the search for safer alternatives to glucocorticoid therapy, DAGR (PF-0417327) may prove to be a contender. The investigational drug is a selective, high-affinity, dissociated agonist of the glucocorticoid receptor, and appeared to be associated with fewer potential adverse events than are typically seen with glucocorticoids in a phase II trial that compared 8 weeks of the drug against placebo and prednisone.

The findings suggest that DAGR is therapeutically equivalent to prednisone 10 mg once daily, but with side effects comparable with those seen with prednisone 5 mg once daily and with no clinical symptoms of adrenal insufficiency. Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant in Portola Valley, Calif., presented data on the drug during the late-breaker session and discussed the implications of the findings at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON– In the search for safer alternatives to glucocorticoid therapy, DAGR (PF-0417327) may prove to be a contender. The investigational drug is a selective, high-affinity, dissociated agonist of the glucocorticoid receptor, and appeared to be associated with fewer potential adverse events than are typically seen with glucocorticoids in a phase II trial that compared 8 weeks of the drug against placebo and prednisone.

The findings suggest that DAGR is therapeutically equivalent to prednisone 10 mg once daily, but with side effects comparable with those seen with prednisone 5 mg once daily and with no clinical symptoms of adrenal insufficiency. Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant in Portola Valley, Calif., presented data on the drug during the late-breaker session and discussed the implications of the findings at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – Low expression of protein A20 in minor salivary gland tissue appears to be associated with lymphomas in patients with primary Sjögren’s syndrome.

In an interview after his late-breaker presentation at the annual meeting of the American College of Rheumatology, Dr. Svein Joar A. Johnsen of Stavanger (Norway) University Hospital, discussed the implications of his findings and the search for biomarkers of lymphoma risk in these patients.

mdales@frontlinemedcom.com

BOSTON – Low expression of protein A20 in minor salivary gland tissue appears to be associated with lymphomas in patients with primary Sjögren’s syndrome.

In an interview after his late-breaker presentation at the annual meeting of the American College of Rheumatology, Dr. Svein Joar A. Johnsen of Stavanger (Norway) University Hospital, discussed the implications of his findings and the search for biomarkers of lymphoma risk in these patients.

mdales@frontlinemedcom.com

BOSTON – Low expression of protein A20 in minor salivary gland tissue appears to be associated with lymphomas in patients with primary Sjögren’s syndrome.

In an interview after his late-breaker presentation at the annual meeting of the American College of Rheumatology, Dr. Svein Joar A. Johnsen of Stavanger (Norway) University Hospital, discussed the implications of his findings and the search for biomarkers of lymphoma risk in these patients.

mdales@frontlinemedcom.com