Rheumatoid Arthritis

SAN FRANCISCO – Patients who initiate triple therapy for rheumatoid arthritis appear to have lower persistence in filling the prescriptions and lower adherence to the regimen even when prescriptions are dispensed for the drugs, compared with users of combination therapy with a tumor necrosis factor inhibitor plus methotrexate in two Veterans Affairs studies.

The studies also suggest that the similar efficacy and patient adherence for both triple therapy and combination therapy with a tumor necrosis factor inhibitor (TNFi) plus methotrexate that have been observed in randomized controlled trials (RCTs) do not accurately portray what occurs in real-world clinical practice.

In one study, Brian C. Sauer, Ph.D., of the University of Utah, Salt Lake City, and coinvestigators utilized the historical data available for utilized the historical data available for 4,364 U.S. veterans over 28 years of age treated for RA from 2006 through 2012. Patients needed to be enrolled with Veterans Affairs for about 6 months prior to and 12 months after the initiation of the triple therapy. The triple therapy involved 3,204 patients. The three drugs could be initiated concomitantly, in an approach that is typical of an RCT design, or could be introduced at different times, with the requirement of an overlapping period of use of all three. For the combination therapy used in 1,160 patients, the two drugs needed to overlap by at least 1 day. When various algorithms that accounted for clinician-mandated shifts in drug use according to patient response to treatment were used, the persistence outcomes could be calculated, with patients judged to be adherent or nonadherent to either treatment regimen.

At 12 months, the rate of persistence in staying on triple therapy ranged from 29% to 50% and for TNFi/methotrexate from 42% to 59%, according to three definitions of persistence the investigators used. Adherence of greater than 80% during the year to the regimens occurred in 17% on triple therapy and 24% on TNFi/methotrexate. The advantage for the combination therapy persisted when factors likely to affect treatment choice and persistence were accounted for in propensity scoring of 1,143 patients from each group.

“We did not evaluate early side effects. Our study focused on 1-year persistence. Similar early drop-off between the groups and RCTs suggest that the treatments have similar tolerability. The fact that patients on triple therapy appeared to be sicker also suggests that providers are possibly concerned about TNF [inhibitor] side effects in the population treated with triple therapy,” Dr. Sauer said at the annual meeting of the American College of Rheumatology.

The additional complexity of triple therapy might also have contributed to the lower adherence, he said.

A second, similar VA study that was presented at the meeting examined patients who had an inadequate response to methotrexate monotherapy found similar results in a comparison of 2,125 patients who added a TNFi to methotrexate with 171 patients who added sulfasalazine and hydroxychloroquine, a scenario that has been tested in RCTs. In this study, 18% persisted in staying on triple therapy over a year, compared with 43% on TNFi/methotrexate, while 12-month adherence rates were 11% and 25%, respectively.

Dr. Sauer reported financial disclosures involving research grant support from Amgen.

SAN FRANCISCO – Patients who initiate triple therapy for rheumatoid arthritis appear to have lower persistence in filling the prescriptions and lower adherence to the regimen even when prescriptions are dispensed for the drugs, compared with users of combination therapy with a tumor necrosis factor inhibitor plus methotrexate in two Veterans Affairs studies.

The studies also suggest that the similar efficacy and patient adherence for both triple therapy and combination therapy with a tumor necrosis factor inhibitor (TNFi) plus methotrexate that have been observed in randomized controlled trials (RCTs) do not accurately portray what occurs in real-world clinical practice.

In one study, Brian C. Sauer, Ph.D., of the University of Utah, Salt Lake City, and coinvestigators utilized the historical data available for utilized the historical data available for 4,364 U.S. veterans over 28 years of age treated for RA from 2006 through 2012. Patients needed to be enrolled with Veterans Affairs for about 6 months prior to and 12 months after the initiation of the triple therapy. The triple therapy involved 3,204 patients. The three drugs could be initiated concomitantly, in an approach that is typical of an RCT design, or could be introduced at different times, with the requirement of an overlapping period of use of all three. For the combination therapy used in 1,160 patients, the two drugs needed to overlap by at least 1 day. When various algorithms that accounted for clinician-mandated shifts in drug use according to patient response to treatment were used, the persistence outcomes could be calculated, with patients judged to be adherent or nonadherent to either treatment regimen.

At 12 months, the rate of persistence in staying on triple therapy ranged from 29% to 50% and for TNFi/methotrexate from 42% to 59%, according to three definitions of persistence the investigators used. Adherence of greater than 80% during the year to the regimens occurred in 17% on triple therapy and 24% on TNFi/methotrexate. The advantage for the combination therapy persisted when factors likely to affect treatment choice and persistence were accounted for in propensity scoring of 1,143 patients from each group.

“We did not evaluate early side effects. Our study focused on 1-year persistence. Similar early drop-off between the groups and RCTs suggest that the treatments have similar tolerability. The fact that patients on triple therapy appeared to be sicker also suggests that providers are possibly concerned about TNF [inhibitor] side effects in the population treated with triple therapy,” Dr. Sauer said at the annual meeting of the American College of Rheumatology.

The additional complexity of triple therapy might also have contributed to the lower adherence, he said.

A second, similar VA study that was presented at the meeting examined patients who had an inadequate response to methotrexate monotherapy found similar results in a comparison of 2,125 patients who added a TNFi to methotrexate with 171 patients who added sulfasalazine and hydroxychloroquine, a scenario that has been tested in RCTs. In this study, 18% persisted in staying on triple therapy over a year, compared with 43% on TNFi/methotrexate, while 12-month adherence rates were 11% and 25%, respectively.

Dr. Sauer reported financial disclosures involving research grant support from Amgen.

SAN FRANCISCO – Patients who initiate triple therapy for rheumatoid arthritis appear to have lower persistence in filling the prescriptions and lower adherence to the regimen even when prescriptions are dispensed for the drugs, compared with users of combination therapy with a tumor necrosis factor inhibitor plus methotrexate in two Veterans Affairs studies.

The studies also suggest that the similar efficacy and patient adherence for both triple therapy and combination therapy with a tumor necrosis factor inhibitor (TNFi) plus methotrexate that have been observed in randomized controlled trials (RCTs) do not accurately portray what occurs in real-world clinical practice.

In one study, Brian C. Sauer, Ph.D., of the University of Utah, Salt Lake City, and coinvestigators utilized the historical data available for utilized the historical data available for 4,364 U.S. veterans over 28 years of age treated for RA from 2006 through 2012. Patients needed to be enrolled with Veterans Affairs for about 6 months prior to and 12 months after the initiation of the triple therapy. The triple therapy involved 3,204 patients. The three drugs could be initiated concomitantly, in an approach that is typical of an RCT design, or could be introduced at different times, with the requirement of an overlapping period of use of all three. For the combination therapy used in 1,160 patients, the two drugs needed to overlap by at least 1 day. When various algorithms that accounted for clinician-mandated shifts in drug use according to patient response to treatment were used, the persistence outcomes could be calculated, with patients judged to be adherent or nonadherent to either treatment regimen.

At 12 months, the rate of persistence in staying on triple therapy ranged from 29% to 50% and for TNFi/methotrexate from 42% to 59%, according to three definitions of persistence the investigators used. Adherence of greater than 80% during the year to the regimens occurred in 17% on triple therapy and 24% on TNFi/methotrexate. The advantage for the combination therapy persisted when factors likely to affect treatment choice and persistence were accounted for in propensity scoring of 1,143 patients from each group.

“We did not evaluate early side effects. Our study focused on 1-year persistence. Similar early drop-off between the groups and RCTs suggest that the treatments have similar tolerability. The fact that patients on triple therapy appeared to be sicker also suggests that providers are possibly concerned about TNF [inhibitor] side effects in the population treated with triple therapy,” Dr. Sauer said at the annual meeting of the American College of Rheumatology.

The additional complexity of triple therapy might also have contributed to the lower adherence, he said.

A second, similar VA study that was presented at the meeting examined patients who had an inadequate response to methotrexate monotherapy found similar results in a comparison of 2,125 patients who added a TNFi to methotrexate with 171 patients who added sulfasalazine and hydroxychloroquine, a scenario that has been tested in RCTs. In this study, 18% persisted in staying on triple therapy over a year, compared with 43% on TNFi/methotrexate, while 12-month adherence rates were 11% and 25%, respectively.

Dr. Sauer reported financial disclosures involving research grant support from Amgen.

SAN FRANCISCO – Triple therapy for rheumatoid arthritis has shone in clinical trials, but its adoption by rheumatologists in the trenches of patient care has been lukewarm.

The challenges facing triple therapy were highlighted in two presentations at the annual meeting of the American College of Rheumatology.

In the first, Dr. Jeffrey Sparks noted that findings from several randomized clinical trials have established the noninferiority of triple therapy with methotrexate (MTX), sulfasazine (SUL), and hydroxychloroquine (HCQ), compared with the combination of MTX and tumor necrosis factor inhibitor. Triple therapy also yields comparable quality of life and is delivered at less cost. Reflecting the evidence, triple therapy is an American College of Rheumatology–recommended option for first-line therapy for high disease activity and poor prognosis, and following failure of nonbiologic disease-modifying antirheumatic drugs (DMARDs). “The many options available add to the complexity of RA treatment decisions. It is unclear whether data supporting triple-therapy use have affected prescribing patterns in typical practice in the United States,” said Dr. Sparks of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Harvard Medical School, Boston.

Longitudinal data available in the Aetna U.S. insurance claims and Veterans Administration databases allowed a look at the issue. The databases were scrutinized from mid-2009 to mid-2014, and from 2006 through 2012, respectively. The age range was broad – 18 years and older. Of the 24,576 eligible subjects identified in the Aetna insurance claims database, the initial treatment was intensified in 2,920 (11.9%) subjects. Almost all (n = 2,739) involved biologic DMARDs, with only 181 (0.7%) intensifying to triple therapy. The frequency of triple therapy was unrelated to calendar time. Use of triple therapy was not associated with patients’ sex, household income, antimicrobial or opioid use, hospitalization for serious infection, and/or comorbidities.

“Triple therapy was infrequently used for RA treatment in this large nationwide study, reflecting typical clinical practice. Use of steroids and nonsteroidal anti-inflammatory drugs prior to initial nonbiologic DMARD treatment, and geographic location, with more frequent use in the northeastern U.S.A., were associated with triple therapy use,” said Dr. Sparks.

Clinician reluctance to move from the conventional therapy and problems with patient adherence are likely factors in the stalled adoption of triple therapy, Dr. Sparks speculated.

During a separate presentation, Dr. Grant W. Cannon said that the disconnection between randomized controlled trial (RCT) data and the reality of clinical practice also extends to the pattern of drug use in triple therapy. In the VA population, the pattern of introduction of MTX, SUL, and HCQ spanned all possible combinations including the concomitant introduction typical of a RCT. The RCT pattern was infrequent, involving only 20% of the patients. The remaining 80% of cases involved the various patterns of drug introduction, with 57% of patients treated by sequential introduction of the individual DMARDs. No appreciable differences in baseline characteristics were apparent.

Calculation of persistence on therapy revealed that patients were significantly less likely to stay on triple therapy when it was introduced in the RCT style of administering all three DMARDs concomitantly (P less than .01). Adherence to therapy was also worse, although not statistically significantly (P = .096).

“Understanding provider practices with the initiation of triple-drug therapy is important as these practices might impact treatment effectiveness,” said Dr. Cannon of the division of rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City. “Since clinical response and patient experience during sequential DMARD initiation may affect decisions to progress to triple therapy, RCT results describing the benefits of triple therapy may not generalize to clinical practice.”

SAN FRANCISCO – Triple therapy for rheumatoid arthritis has shone in clinical trials, but its adoption by rheumatologists in the trenches of patient care has been lukewarm.

The challenges facing triple therapy were highlighted in two presentations at the annual meeting of the American College of Rheumatology.

In the first, Dr. Jeffrey Sparks noted that findings from several randomized clinical trials have established the noninferiority of triple therapy with methotrexate (MTX), sulfasazine (SUL), and hydroxychloroquine (HCQ), compared with the combination of MTX and tumor necrosis factor inhibitor. Triple therapy also yields comparable quality of life and is delivered at less cost. Reflecting the evidence, triple therapy is an American College of Rheumatology–recommended option for first-line therapy for high disease activity and poor prognosis, and following failure of nonbiologic disease-modifying antirheumatic drugs (DMARDs). “The many options available add to the complexity of RA treatment decisions. It is unclear whether data supporting triple-therapy use have affected prescribing patterns in typical practice in the United States,” said Dr. Sparks of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Harvard Medical School, Boston.

Longitudinal data available in the Aetna U.S. insurance claims and Veterans Administration databases allowed a look at the issue. The databases were scrutinized from mid-2009 to mid-2014, and from 2006 through 2012, respectively. The age range was broad – 18 years and older. Of the 24,576 eligible subjects identified in the Aetna insurance claims database, the initial treatment was intensified in 2,920 (11.9%) subjects. Almost all (n = 2,739) involved biologic DMARDs, with only 181 (0.7%) intensifying to triple therapy. The frequency of triple therapy was unrelated to calendar time. Use of triple therapy was not associated with patients’ sex, household income, antimicrobial or opioid use, hospitalization for serious infection, and/or comorbidities.

“Triple therapy was infrequently used for RA treatment in this large nationwide study, reflecting typical clinical practice. Use of steroids and nonsteroidal anti-inflammatory drugs prior to initial nonbiologic DMARD treatment, and geographic location, with more frequent use in the northeastern U.S.A., were associated with triple therapy use,” said Dr. Sparks.

Clinician reluctance to move from the conventional therapy and problems with patient adherence are likely factors in the stalled adoption of triple therapy, Dr. Sparks speculated.

During a separate presentation, Dr. Grant W. Cannon said that the disconnection between randomized controlled trial (RCT) data and the reality of clinical practice also extends to the pattern of drug use in triple therapy. In the VA population, the pattern of introduction of MTX, SUL, and HCQ spanned all possible combinations including the concomitant introduction typical of a RCT. The RCT pattern was infrequent, involving only 20% of the patients. The remaining 80% of cases involved the various patterns of drug introduction, with 57% of patients treated by sequential introduction of the individual DMARDs. No appreciable differences in baseline characteristics were apparent.

Calculation of persistence on therapy revealed that patients were significantly less likely to stay on triple therapy when it was introduced in the RCT style of administering all three DMARDs concomitantly (P less than .01). Adherence to therapy was also worse, although not statistically significantly (P = .096).

“Understanding provider practices with the initiation of triple-drug therapy is important as these practices might impact treatment effectiveness,” said Dr. Cannon of the division of rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City. “Since clinical response and patient experience during sequential DMARD initiation may affect decisions to progress to triple therapy, RCT results describing the benefits of triple therapy may not generalize to clinical practice.”

SAN FRANCISCO – Triple therapy for rheumatoid arthritis has shone in clinical trials, but its adoption by rheumatologists in the trenches of patient care has been lukewarm.

The challenges facing triple therapy were highlighted in two presentations at the annual meeting of the American College of Rheumatology.

In the first, Dr. Jeffrey Sparks noted that findings from several randomized clinical trials have established the noninferiority of triple therapy with methotrexate (MTX), sulfasazine (SUL), and hydroxychloroquine (HCQ), compared with the combination of MTX and tumor necrosis factor inhibitor. Triple therapy also yields comparable quality of life and is delivered at less cost. Reflecting the evidence, triple therapy is an American College of Rheumatology–recommended option for first-line therapy for high disease activity and poor prognosis, and following failure of nonbiologic disease-modifying antirheumatic drugs (DMARDs). “The many options available add to the complexity of RA treatment decisions. It is unclear whether data supporting triple-therapy use have affected prescribing patterns in typical practice in the United States,” said Dr. Sparks of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Harvard Medical School, Boston.

Longitudinal data available in the Aetna U.S. insurance claims and Veterans Administration databases allowed a look at the issue. The databases were scrutinized from mid-2009 to mid-2014, and from 2006 through 2012, respectively. The age range was broad – 18 years and older. Of the 24,576 eligible subjects identified in the Aetna insurance claims database, the initial treatment was intensified in 2,920 (11.9%) subjects. Almost all (n = 2,739) involved biologic DMARDs, with only 181 (0.7%) intensifying to triple therapy. The frequency of triple therapy was unrelated to calendar time. Use of triple therapy was not associated with patients’ sex, household income, antimicrobial or opioid use, hospitalization for serious infection, and/or comorbidities.

“Triple therapy was infrequently used for RA treatment in this large nationwide study, reflecting typical clinical practice. Use of steroids and nonsteroidal anti-inflammatory drugs prior to initial nonbiologic DMARD treatment, and geographic location, with more frequent use in the northeastern U.S.A., were associated with triple therapy use,” said Dr. Sparks.

Clinician reluctance to move from the conventional therapy and problems with patient adherence are likely factors in the stalled adoption of triple therapy, Dr. Sparks speculated.

During a separate presentation, Dr. Grant W. Cannon said that the disconnection between randomized controlled trial (RCT) data and the reality of clinical practice also extends to the pattern of drug use in triple therapy. In the VA population, the pattern of introduction of MTX, SUL, and HCQ spanned all possible combinations including the concomitant introduction typical of a RCT. The RCT pattern was infrequent, involving only 20% of the patients. The remaining 80% of cases involved the various patterns of drug introduction, with 57% of patients treated by sequential introduction of the individual DMARDs. No appreciable differences in baseline characteristics were apparent.

Calculation of persistence on therapy revealed that patients were significantly less likely to stay on triple therapy when it was introduced in the RCT style of administering all three DMARDs concomitantly (P less than .01). Adherence to therapy was also worse, although not statistically significantly (P = .096).

“Understanding provider practices with the initiation of triple-drug therapy is important as these practices might impact treatment effectiveness,” said Dr. Cannon of the division of rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City. “Since clinical response and patient experience during sequential DMARD initiation may affect decisions to progress to triple therapy, RCT results describing the benefits of triple therapy may not generalize to clinical practice.”

SAN FRANCISCO – Sarilumab, an investigational monoclonal antibody directed against the IL-6 receptor, demonstrated efficacy at two different dose levels, compared with placebo, in patients with active rheumatoid arthritis (RA) who were intolerant to or had inadequate response to anti–tumor necrosis factor (anti-TNF) inhibitors in the pivotal phase III TARGET study.

On all measures of disease activity and physical function, sarilumab was significantly superior to placebo in these very sick patients. Results were presented at the annual meeting of the American College of Rheumatology.

“New treatments are needed to address unmet patient needs, including the failure to respond to therapy. Sarilumab, if approved, may be a potential option for RA patients with moderate to severe RA,” said Dr. Roy Fleischmann of University of Texas in Dallas.

“Both the 150-mg and 200-mg doses of sarilumab demonstrate improvement and clinical efficacy versus placebo in these patients. The higher dose appears to have slightly better efficacy but also had a higher incidence of treatment-emergent adverse events leading to discontinuations. The 150-mg dose may be a little safer. I would start with 200 mg and methotrexate and if an adverse event occurred, lower the dose to 150 mg,” Dr. Fleischmann told the audience.

TARGET enrolled 546 patients with active RA for at least 6 months who were intolerant to or failed prior anti-TNF therapy. Active disease was defined as at least six swollen and eight tender joints. All patients had high C-reactive protein (CRP) levels at screening (more than 8 mg/L).

The patients’ median age was 52 years, and 80% were female. Median duration of RA was 12 years. Twenty-five percent had been treated with more than one prior anti-TNF agent. About 74% were rheumatoid factor positive.

“These were recalcitrant and sick RA patients,” Dr. Fleischmann said.

Patients were randomized to sarilumab 150 mg, 200 mg, or placebo in addition to background conventional DMARD therapy. Study drugs and placebo were self-administered subcutaneously every other week. Patients who did not respond adequately to therapy at week 12 were rescued with sarilumab 200 mg every 2 weeks.

“Both doses of sarilumab had significantly improved ACR 20/50/70 response, compared with placebo,” he said.

Mean change from baseline to week 12 in Health Assessment Questionnaire–Disease Index (HAQ-DI), which assesses daily physical function, was –0.49, –0.50, and –0.29 in the 200-mg, 150-mg, and placebo groups, respectively (P = .0004 and P = .0007, respectively, for each dose of sarilumab).

The percentage of patients with an ACR 20 response at week 24 was 61%, 56%, and 34%, for the 200-mg, 150-mg, and placebo groups, respectively (P less than .0001, for both comparisons).

Sarilumab was also superior to placebo for all secondary endpoints, including the percentage of patients achieving an ACR 50 and ACR 70 response, change from baseline in Disease Activity Score (DAS) 28-CRP, achieving DAS28-CRP less than 2.6, change from baseline in clinical disease activity index (CDAI), and change in HAQ-DI at week 24.

Looking at safety, treatment-emergent adverse events were more frequent in the sarilumab-treated patients, compared with placebo: 65% for the 200-mg dose, 66% for the 150-mg dose, versus 50% for placebo. Serious adverse events were more frequent in the sarilumab 200-mg group, compared with placebo (5% versus 3%), and were similar to placebo in the sarilumab 150-mg group (3%)

Serious infections occurred in two patients in the sarilumab 200-mg group, one patient in the sarilumab 150-mg group, and two patients on placebo. Neutropenia and infection were the most frequent adverse events leading to treatment discontinuations (17 in the 200-mg group, 14 in the 150-mg group).

Regeneron Pharmaceuticals and Sanofi funded the study. Dr. Fleischmann disclosed financial ties with Abbvie, Akros, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Pharmaceutica Products, Eli Lilly & Co., Merck Pharmaceuticals, Pfizer, Resolve, Roche Pharmaceuticals, Sanofi-Aventis Pharmaceuticals, and UCB.

SAN FRANCISCO – Sarilumab, an investigational monoclonal antibody directed against the IL-6 receptor, demonstrated efficacy at two different dose levels, compared with placebo, in patients with active rheumatoid arthritis (RA) who were intolerant to or had inadequate response to anti–tumor necrosis factor (anti-TNF) inhibitors in the pivotal phase III TARGET study.

On all measures of disease activity and physical function, sarilumab was significantly superior to placebo in these very sick patients. Results were presented at the annual meeting of the American College of Rheumatology.

“New treatments are needed to address unmet patient needs, including the failure to respond to therapy. Sarilumab, if approved, may be a potential option for RA patients with moderate to severe RA,” said Dr. Roy Fleischmann of University of Texas in Dallas.

“Both the 150-mg and 200-mg doses of sarilumab demonstrate improvement and clinical efficacy versus placebo in these patients. The higher dose appears to have slightly better efficacy but also had a higher incidence of treatment-emergent adverse events leading to discontinuations. The 150-mg dose may be a little safer. I would start with 200 mg and methotrexate and if an adverse event occurred, lower the dose to 150 mg,” Dr. Fleischmann told the audience.

TARGET enrolled 546 patients with active RA for at least 6 months who were intolerant to or failed prior anti-TNF therapy. Active disease was defined as at least six swollen and eight tender joints. All patients had high C-reactive protein (CRP) levels at screening (more than 8 mg/L).

The patients’ median age was 52 years, and 80% were female. Median duration of RA was 12 years. Twenty-five percent had been treated with more than one prior anti-TNF agent. About 74% were rheumatoid factor positive.

“These were recalcitrant and sick RA patients,” Dr. Fleischmann said.

Patients were randomized to sarilumab 150 mg, 200 mg, or placebo in addition to background conventional DMARD therapy. Study drugs and placebo were self-administered subcutaneously every other week. Patients who did not respond adequately to therapy at week 12 were rescued with sarilumab 200 mg every 2 weeks.

“Both doses of sarilumab had significantly improved ACR 20/50/70 response, compared with placebo,” he said.

Mean change from baseline to week 12 in Health Assessment Questionnaire–Disease Index (HAQ-DI), which assesses daily physical function, was –0.49, –0.50, and –0.29 in the 200-mg, 150-mg, and placebo groups, respectively (P = .0004 and P = .0007, respectively, for each dose of sarilumab).

The percentage of patients with an ACR 20 response at week 24 was 61%, 56%, and 34%, for the 200-mg, 150-mg, and placebo groups, respectively (P less than .0001, for both comparisons).

Sarilumab was also superior to placebo for all secondary endpoints, including the percentage of patients achieving an ACR 50 and ACR 70 response, change from baseline in Disease Activity Score (DAS) 28-CRP, achieving DAS28-CRP less than 2.6, change from baseline in clinical disease activity index (CDAI), and change in HAQ-DI at week 24.

Looking at safety, treatment-emergent adverse events were more frequent in the sarilumab-treated patients, compared with placebo: 65% for the 200-mg dose, 66% for the 150-mg dose, versus 50% for placebo. Serious adverse events were more frequent in the sarilumab 200-mg group, compared with placebo (5% versus 3%), and were similar to placebo in the sarilumab 150-mg group (3%)

Serious infections occurred in two patients in the sarilumab 200-mg group, one patient in the sarilumab 150-mg group, and two patients on placebo. Neutropenia and infection were the most frequent adverse events leading to treatment discontinuations (17 in the 200-mg group, 14 in the 150-mg group).

Regeneron Pharmaceuticals and Sanofi funded the study. Dr. Fleischmann disclosed financial ties with Abbvie, Akros, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Pharmaceutica Products, Eli Lilly & Co., Merck Pharmaceuticals, Pfizer, Resolve, Roche Pharmaceuticals, Sanofi-Aventis Pharmaceuticals, and UCB.

SAN FRANCISCO – Sarilumab, an investigational monoclonal antibody directed against the IL-6 receptor, demonstrated efficacy at two different dose levels, compared with placebo, in patients with active rheumatoid arthritis (RA) who were intolerant to or had inadequate response to anti–tumor necrosis factor (anti-TNF) inhibitors in the pivotal phase III TARGET study.

On all measures of disease activity and physical function, sarilumab was significantly superior to placebo in these very sick patients. Results were presented at the annual meeting of the American College of Rheumatology.

“New treatments are needed to address unmet patient needs, including the failure to respond to therapy. Sarilumab, if approved, may be a potential option for RA patients with moderate to severe RA,” said Dr. Roy Fleischmann of University of Texas in Dallas.

“Both the 150-mg and 200-mg doses of sarilumab demonstrate improvement and clinical efficacy versus placebo in these patients. The higher dose appears to have slightly better efficacy but also had a higher incidence of treatment-emergent adverse events leading to discontinuations. The 150-mg dose may be a little safer. I would start with 200 mg and methotrexate and if an adverse event occurred, lower the dose to 150 mg,” Dr. Fleischmann told the audience.

TARGET enrolled 546 patients with active RA for at least 6 months who were intolerant to or failed prior anti-TNF therapy. Active disease was defined as at least six swollen and eight tender joints. All patients had high C-reactive protein (CRP) levels at screening (more than 8 mg/L).

The patients’ median age was 52 years, and 80% were female. Median duration of RA was 12 years. Twenty-five percent had been treated with more than one prior anti-TNF agent. About 74% were rheumatoid factor positive.

“These were recalcitrant and sick RA patients,” Dr. Fleischmann said.

Patients were randomized to sarilumab 150 mg, 200 mg, or placebo in addition to background conventional DMARD therapy. Study drugs and placebo were self-administered subcutaneously every other week. Patients who did not respond adequately to therapy at week 12 were rescued with sarilumab 200 mg every 2 weeks.

“Both doses of sarilumab had significantly improved ACR 20/50/70 response, compared with placebo,” he said.

Mean change from baseline to week 12 in Health Assessment Questionnaire–Disease Index (HAQ-DI), which assesses daily physical function, was –0.49, –0.50, and –0.29 in the 200-mg, 150-mg, and placebo groups, respectively (P = .0004 and P = .0007, respectively, for each dose of sarilumab).

The percentage of patients with an ACR 20 response at week 24 was 61%, 56%, and 34%, for the 200-mg, 150-mg, and placebo groups, respectively (P less than .0001, for both comparisons).

Sarilumab was also superior to placebo for all secondary endpoints, including the percentage of patients achieving an ACR 50 and ACR 70 response, change from baseline in Disease Activity Score (DAS) 28-CRP, achieving DAS28-CRP less than 2.6, change from baseline in clinical disease activity index (CDAI), and change in HAQ-DI at week 24.

Looking at safety, treatment-emergent adverse events were more frequent in the sarilumab-treated patients, compared with placebo: 65% for the 200-mg dose, 66% for the 150-mg dose, versus 50% for placebo. Serious adverse events were more frequent in the sarilumab 200-mg group, compared with placebo (5% versus 3%), and were similar to placebo in the sarilumab 150-mg group (3%)

Serious infections occurred in two patients in the sarilumab 200-mg group, one patient in the sarilumab 150-mg group, and two patients on placebo. Neutropenia and infection were the most frequent adverse events leading to treatment discontinuations (17 in the 200-mg group, 14 in the 150-mg group).

Regeneron Pharmaceuticals and Sanofi funded the study. Dr. Fleischmann disclosed financial ties with Abbvie, Akros, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Pharmaceutica Products, Eli Lilly & Co., Merck Pharmaceuticals, Pfizer, Resolve, Roche Pharmaceuticals, Sanofi-Aventis Pharmaceuticals, and UCB.

SAN FRANCISCO – Baricitinib, an investigational oral investigational JAK 1/2 inhibitor, was significantly superior to adalimumab and to placebo in the treatment of patients with active rheumatoid arthritis despite background methotrexate in the phase III RA-BEAM study.

Patients taking baricitinib had significant improvements in signs and symptoms of rheumatoid arthritis (RA), physical function, and patient-reported outcomes. These encouraging results, reported at a late-breaking abstract session during the annual meeting of the American College of Rheumatology, come on the heels of other positive phase III studies of this drug in treatment-naive patients and those with an inadequate response to anti-TNF agents plus methotrexate.

“I feel that this is a real clinical benefit we see with baricitinib, but we will need further studies. The safety and tolerability of baricitinib are satisfactory and consistent with other phase II and III studies reported at this meeting,” said Dr. Peter Taylor of the Kennedy Institute of Rheumatology at University of Oxford (England).

“The most important finding is that baricitinib administered with methotrexate is a superior treatment to methotrexate alone, but another interesting finding is that the baricitinib/methotrexate combination was superior to adalimumab [Humira] plus methotrexate,” Dr. Taylor added.

“Baricitinib is an oral, highly selective inhibitor of JAK 2, and the drug improves disease activity with acceptable safety in patients with an inadequate response to conventional therapy and also in disease-modifying antirheumatic drug [DMARD]-naive patients with rheumatoid arthritis,” Dr. Taylor told the audience.

The RA-BEAM study enrolled 1,307 RA patients who had an inadequate response to methotrexate. Patients were randomized 3:3:2 to placebo, baricitinib 4 mg/day or adalimumab 40 mg biweekly. From week 16 on, nonresponders were rescued with 4 mg baricitinib. All patients continued on stable doses of background methotrexate.

Median age of the patients was 50 years, and a majority were seropositive for rheumatoid factor. The mean methotrexate dose was 15 mg/once weekly, and 60% of patients were taking concomitant oral glucocorticoids.

At baseline, groups were well balanced for disease activity, disease duration, and demographic characteristics. The mean number of swollen joints was 16 and mean number of tender joints 23.

“These patients had marked disability and high baseline disease activity,” Dr. Taylor said.

At week 24, about 84%-90% of patients remained on study, and at week 52, more than 80% were still on study.

Rescue rates were 26% for placebo patients, 7% for baricitinib-treated patients, and 12% for those randomized to adalimumab.

For the primary endpoint of at least a 20% response at 12 weeks according to ACR criteria (i.e., ACR20), baricitinib was superior to both adalimumab and placebo (plus methotrexate in all three arms). ACR20 was achieved in 40% of patients in the placebo arm, 61% of those in the adalimumab arm, and by 70% of those taking baricitinib (P less than .001 for both comparisons versus placebo).

At week 24, the same pattern was observed for ACR20, ACR50, and ACR70. An ACR20 response was achieved by 37% with placebo, 66% with adalimumab, and 74% with baricitinib. For ACR50, response rates were 19%, 46%, and 50%, respectively. For ACR70, response rates were 9%, 22%, and 30%, respectively. (The P value was less than .001 for all comparisons versus placebo.)

Significantly more patients in the baricitinib-plus-methotrexate arm achieved low disease activity or remission, compared with placebo and with adalimumab plus methotrexate. Over time, the benefits increased in the baricitinib arm.

“A rapid reduction was observed in the number of swollen joints and tender joints with baricitinib and adalimumab, but the reduction was deeper with baricitinib,” said Dr. Taylor. “Patient-reported outcomes, such as joint stiffness and pain and fatigue, were improved on baricitinib as early as week 1, compared with placebo.

Both baricitinib and adalimumab achieved a greater inhibition on structural damage, compared with placebo, and this difference was maintained at week 52.

The percentage of patients with no change in Sharp van der Heijde Score was 70% for placebo, 79% for baricitinib, and 81% for adalimumab.

Rates of treatment-emergent adverse events were higher for the active treatment groups versus placebo: during weeks 0-12, 47.3% for placebo, 52.8% for baricitinib, and 50.9% for adalimumab. Infection rates during weeks 0-12 were 17.8%, 21.8%, and 20%, respectively.

The rates of serious adverse events during weeks 0-12 were 2.7% for placebo, 2.3% for baricitinib, and 1.2% for adalimumab, respectively. During an additional 12 weeks they rose further to 4.3%, 4.5%, and 1.8%, respectively.

There were four cases of malignancy reported in the baricitinib group and none in the adalimumab group in weeks 0-24. Two deaths were reported in the baricitinib group and none in the other two groups.

If baricitinib gains Food and Drug Administration approval for the treatment of RA, Dr. Taylor predicted that as experience is gained, it will be used “relatively early” in the course of treatment, but he acknowledged that cost will enter into the discussion.

Eli Lilly & Co. and Incyte Corporation sponsored the study. All investigators reported ties with Lilly, and some had ties with other companies marketing RA drugs.

SAN FRANCISCO – Baricitinib, an investigational oral investigational JAK 1/2 inhibitor, was significantly superior to adalimumab and to placebo in the treatment of patients with active rheumatoid arthritis despite background methotrexate in the phase III RA-BEAM study.

Patients taking baricitinib had significant improvements in signs and symptoms of rheumatoid arthritis (RA), physical function, and patient-reported outcomes. These encouraging results, reported at a late-breaking abstract session during the annual meeting of the American College of Rheumatology, come on the heels of other positive phase III studies of this drug in treatment-naive patients and those with an inadequate response to anti-TNF agents plus methotrexate.

“I feel that this is a real clinical benefit we see with baricitinib, but we will need further studies. The safety and tolerability of baricitinib are satisfactory and consistent with other phase II and III studies reported at this meeting,” said Dr. Peter Taylor of the Kennedy Institute of Rheumatology at University of Oxford (England).

“The most important finding is that baricitinib administered with methotrexate is a superior treatment to methotrexate alone, but another interesting finding is that the baricitinib/methotrexate combination was superior to adalimumab [Humira] plus methotrexate,” Dr. Taylor added.

“Baricitinib is an oral, highly selective inhibitor of JAK 2, and the drug improves disease activity with acceptable safety in patients with an inadequate response to conventional therapy and also in disease-modifying antirheumatic drug [DMARD]-naive patients with rheumatoid arthritis,” Dr. Taylor told the audience.

The RA-BEAM study enrolled 1,307 RA patients who had an inadequate response to methotrexate. Patients were randomized 3:3:2 to placebo, baricitinib 4 mg/day or adalimumab 40 mg biweekly. From week 16 on, nonresponders were rescued with 4 mg baricitinib. All patients continued on stable doses of background methotrexate.

Median age of the patients was 50 years, and a majority were seropositive for rheumatoid factor. The mean methotrexate dose was 15 mg/once weekly, and 60% of patients were taking concomitant oral glucocorticoids.

At baseline, groups were well balanced for disease activity, disease duration, and demographic characteristics. The mean number of swollen joints was 16 and mean number of tender joints 23.

“These patients had marked disability and high baseline disease activity,” Dr. Taylor said.

At week 24, about 84%-90% of patients remained on study, and at week 52, more than 80% were still on study.

Rescue rates were 26% for placebo patients, 7% for baricitinib-treated patients, and 12% for those randomized to adalimumab.

For the primary endpoint of at least a 20% response at 12 weeks according to ACR criteria (i.e., ACR20), baricitinib was superior to both adalimumab and placebo (plus methotrexate in all three arms). ACR20 was achieved in 40% of patients in the placebo arm, 61% of those in the adalimumab arm, and by 70% of those taking baricitinib (P less than .001 for both comparisons versus placebo).

At week 24, the same pattern was observed for ACR20, ACR50, and ACR70. An ACR20 response was achieved by 37% with placebo, 66% with adalimumab, and 74% with baricitinib. For ACR50, response rates were 19%, 46%, and 50%, respectively. For ACR70, response rates were 9%, 22%, and 30%, respectively. (The P value was less than .001 for all comparisons versus placebo.)

Significantly more patients in the baricitinib-plus-methotrexate arm achieved low disease activity or remission, compared with placebo and with adalimumab plus methotrexate. Over time, the benefits increased in the baricitinib arm.

“A rapid reduction was observed in the number of swollen joints and tender joints with baricitinib and adalimumab, but the reduction was deeper with baricitinib,” said Dr. Taylor. “Patient-reported outcomes, such as joint stiffness and pain and fatigue, were improved on baricitinib as early as week 1, compared with placebo.

Both baricitinib and adalimumab achieved a greater inhibition on structural damage, compared with placebo, and this difference was maintained at week 52.

The percentage of patients with no change in Sharp van der Heijde Score was 70% for placebo, 79% for baricitinib, and 81% for adalimumab.

Rates of treatment-emergent adverse events were higher for the active treatment groups versus placebo: during weeks 0-12, 47.3% for placebo, 52.8% for baricitinib, and 50.9% for adalimumab. Infection rates during weeks 0-12 were 17.8%, 21.8%, and 20%, respectively.

The rates of serious adverse events during weeks 0-12 were 2.7% for placebo, 2.3% for baricitinib, and 1.2% for adalimumab, respectively. During an additional 12 weeks they rose further to 4.3%, 4.5%, and 1.8%, respectively.

There were four cases of malignancy reported in the baricitinib group and none in the adalimumab group in weeks 0-24. Two deaths were reported in the baricitinib group and none in the other two groups.

If baricitinib gains Food and Drug Administration approval for the treatment of RA, Dr. Taylor predicted that as experience is gained, it will be used “relatively early” in the course of treatment, but he acknowledged that cost will enter into the discussion.

Eli Lilly & Co. and Incyte Corporation sponsored the study. All investigators reported ties with Lilly, and some had ties with other companies marketing RA drugs.

SAN FRANCISCO – Baricitinib, an investigational oral investigational JAK 1/2 inhibitor, was significantly superior to adalimumab and to placebo in the treatment of patients with active rheumatoid arthritis despite background methotrexate in the phase III RA-BEAM study.

Patients taking baricitinib had significant improvements in signs and symptoms of rheumatoid arthritis (RA), physical function, and patient-reported outcomes. These encouraging results, reported at a late-breaking abstract session during the annual meeting of the American College of Rheumatology, come on the heels of other positive phase III studies of this drug in treatment-naive patients and those with an inadequate response to anti-TNF agents plus methotrexate.

“I feel that this is a real clinical benefit we see with baricitinib, but we will need further studies. The safety and tolerability of baricitinib are satisfactory and consistent with other phase II and III studies reported at this meeting,” said Dr. Peter Taylor of the Kennedy Institute of Rheumatology at University of Oxford (England).

“The most important finding is that baricitinib administered with methotrexate is a superior treatment to methotrexate alone, but another interesting finding is that the baricitinib/methotrexate combination was superior to adalimumab [Humira] plus methotrexate,” Dr. Taylor added.

“Baricitinib is an oral, highly selective inhibitor of JAK 2, and the drug improves disease activity with acceptable safety in patients with an inadequate response to conventional therapy and also in disease-modifying antirheumatic drug [DMARD]-naive patients with rheumatoid arthritis,” Dr. Taylor told the audience.

The RA-BEAM study enrolled 1,307 RA patients who had an inadequate response to methotrexate. Patients were randomized 3:3:2 to placebo, baricitinib 4 mg/day or adalimumab 40 mg biweekly. From week 16 on, nonresponders were rescued with 4 mg baricitinib. All patients continued on stable doses of background methotrexate.

Median age of the patients was 50 years, and a majority were seropositive for rheumatoid factor. The mean methotrexate dose was 15 mg/once weekly, and 60% of patients were taking concomitant oral glucocorticoids.

At baseline, groups were well balanced for disease activity, disease duration, and demographic characteristics. The mean number of swollen joints was 16 and mean number of tender joints 23.

“These patients had marked disability and high baseline disease activity,” Dr. Taylor said.

At week 24, about 84%-90% of patients remained on study, and at week 52, more than 80% were still on study.

Rescue rates were 26% for placebo patients, 7% for baricitinib-treated patients, and 12% for those randomized to adalimumab.

For the primary endpoint of at least a 20% response at 12 weeks according to ACR criteria (i.e., ACR20), baricitinib was superior to both adalimumab and placebo (plus methotrexate in all three arms). ACR20 was achieved in 40% of patients in the placebo arm, 61% of those in the adalimumab arm, and by 70% of those taking baricitinib (P less than .001 for both comparisons versus placebo).

At week 24, the same pattern was observed for ACR20, ACR50, and ACR70. An ACR20 response was achieved by 37% with placebo, 66% with adalimumab, and 74% with baricitinib. For ACR50, response rates were 19%, 46%, and 50%, respectively. For ACR70, response rates were 9%, 22%, and 30%, respectively. (The P value was less than .001 for all comparisons versus placebo.)

Significantly more patients in the baricitinib-plus-methotrexate arm achieved low disease activity or remission, compared with placebo and with adalimumab plus methotrexate. Over time, the benefits increased in the baricitinib arm.

“A rapid reduction was observed in the number of swollen joints and tender joints with baricitinib and adalimumab, but the reduction was deeper with baricitinib,” said Dr. Taylor. “Patient-reported outcomes, such as joint stiffness and pain and fatigue, were improved on baricitinib as early as week 1, compared with placebo.

Both baricitinib and adalimumab achieved a greater inhibition on structural damage, compared with placebo, and this difference was maintained at week 52.

The percentage of patients with no change in Sharp van der Heijde Score was 70% for placebo, 79% for baricitinib, and 81% for adalimumab.

Rates of treatment-emergent adverse events were higher for the active treatment groups versus placebo: during weeks 0-12, 47.3% for placebo, 52.8% for baricitinib, and 50.9% for adalimumab. Infection rates during weeks 0-12 were 17.8%, 21.8%, and 20%, respectively.

The rates of serious adverse events during weeks 0-12 were 2.7% for placebo, 2.3% for baricitinib, and 1.2% for adalimumab, respectively. During an additional 12 weeks they rose further to 4.3%, 4.5%, and 1.8%, respectively.

There were four cases of malignancy reported in the baricitinib group and none in the adalimumab group in weeks 0-24. Two deaths were reported in the baricitinib group and none in the other two groups.

If baricitinib gains Food and Drug Administration approval for the treatment of RA, Dr. Taylor predicted that as experience is gained, it will be used “relatively early” in the course of treatment, but he acknowledged that cost will enter into the discussion.

Eli Lilly & Co. and Incyte Corporation sponsored the study. All investigators reported ties with Lilly, and some had ties with other companies marketing RA drugs.

SAN FRANCISCO – Vectra DA, a multibiomarker blood test, can predict response to therapy for patients with rheumatoid arthritis, and it can also identify patients who can safely taper and discontinue disease-modifying antirheumatic drug (DMARD) therapy, according to two separate poster presentations at the annual meeting of the American College of Rheumatology.

Management of patients with RA is typically based on clinical criteria and lab test results. Vectra DA is the only multibiomarker panel available for assessing therapeutic response in RA. The test is Medicare-approved, and Medicare allows about $580 per test, according to a spokesperson for Crescendo Bioscience, the company providing the test. Currently, Vectra DA is used in about 20% of RA patients who are actively managed by a rheumatologist in the United States, and about 40% of U.S. rheumatologists use the test at least once per month, the spokesperson said.

Alice Goodman/Frontline Medical News

“Vectra DA can assess the risk of radiographic changes and track therapeutic response. Patients with low to moderate Vectra DA scores have a reduced risk of radiographic progression over the next year,” said a coauthor of the first study, Rebecca J. Bolce, an employee of Crescendo.

Response to subsequent therapy

This retrospective study analyzed multibiomarker disease activity score (that is, Vectra DA) in incomplete responders to 3 months of methotrexate monotherapy to predict response to subsequent triple therapy versus biologic therapies. The patient sample came from the SWEFOT (Swedish Farmacotherapy) study of patients with early RA.

After 3 months of methotrexate therapy, 157 nonresponders were randomized to triple therapy or methotrexate plus infliximab (biologic therapy). At the time of randomization, nonresponders were assessed with Vectra DA. Patients with low Vectra DA scores (that is, less than 30) were successfully treated with triple therapy; at 1 year, 88% of these patients achieved low disease activity (a 28-joint Disease Activity Score [DAS28] less than 3.2), compared with 18% assigned to biologic therapy (P = .006).

Patients with a high score on Vectra DA were more likely to respond to biologics. In this group, at 1 year, low disease activity was achieved in 58% of patients randomized to biologics versus 35% randomized to triple therapy (P = .04).

“At 1 year, the Vectra DA score at 3 months was a superior predictor of response to both conventional triple therapy and biologic therapy, compared with C-reactive protein, erythrocyte sedimentation rate, and DAS28,” Ms. Bolce said.

“These findings may help facilitate and improve the development of individualized and cost-effective treatment plans for individuals with RA,” Ms. Bolce said.

Tapering therapy

A second study analyzed the role of multibiomarker disease activity (Vectra DA score) in predicting relapses in RA patients in sustained remission when tapering disease-modifying antirheumatic drug therapy in the context of the RETRO randomized clinical trial.

On a scale from 0-100, Vectra DA scores of less than 30 are categorized as low, scores 30-44 are called moderate, and those greater than 44 are considered high. Scores were calculated and compared between 94 patients who were relapsing or in sustained remission while tapering DMARD therapy.

Patients were randomized to one of three arms: continuation of DMARD; reduction of DMARD by 50%; or reduction of DMARD by 50% for 6 months and then stopping therapy.

Moderate to high scores were found in one-third of RA patients in remission. Scores were twice as high in relapsing patients (58.3%), compared with those in stable remission (25%). Baseline scores were significantly higher in relapsing patients than in those in stable remission in the entire population, in tapering patients, and in those who stopped DMARDs.

A multivariate analysis found that Vectra DA scores were independent predictors of relapse next to anticitrullinated protein antibody (ACPA) status. Relapse rates were as follows: 13% in VECTRA-low/ACPA-low patients; about one-third in patients positive on one or the other test; and 76.4% in those with high VECTRA DA scores and high ACPA level.

“Vectra DA score improved the prediction of relapses in RA patients in stable remission undergoing DMARD tapering. Combined with ACPA testing, the score allowed a correct identification of relapse in more than 80% of patients,” stated lead author Dr. Juergen Rech of the University of Erlangen-Nuremberg, Germany.

SAN FRANCISCO – Vectra DA, a multibiomarker blood test, can predict response to therapy for patients with rheumatoid arthritis, and it can also identify patients who can safely taper and discontinue disease-modifying antirheumatic drug (DMARD) therapy, according to two separate poster presentations at the annual meeting of the American College of Rheumatology.

Management of patients with RA is typically based on clinical criteria and lab test results. Vectra DA is the only multibiomarker panel available for assessing therapeutic response in RA. The test is Medicare-approved, and Medicare allows about $580 per test, according to a spokesperson for Crescendo Bioscience, the company providing the test. Currently, Vectra DA is used in about 20% of RA patients who are actively managed by a rheumatologist in the United States, and about 40% of U.S. rheumatologists use the test at least once per month, the spokesperson said.

Alice Goodman/Frontline Medical News

“Vectra DA can assess the risk of radiographic changes and track therapeutic response. Patients with low to moderate Vectra DA scores have a reduced risk of radiographic progression over the next year,” said a coauthor of the first study, Rebecca J. Bolce, an employee of Crescendo.

Response to subsequent therapy

This retrospective study analyzed multibiomarker disease activity score (that is, Vectra DA) in incomplete responders to 3 months of methotrexate monotherapy to predict response to subsequent triple therapy versus biologic therapies. The patient sample came from the SWEFOT (Swedish Farmacotherapy) study of patients with early RA.

After 3 months of methotrexate therapy, 157 nonresponders were randomized to triple therapy or methotrexate plus infliximab (biologic therapy). At the time of randomization, nonresponders were assessed with Vectra DA. Patients with low Vectra DA scores (that is, less than 30) were successfully treated with triple therapy; at 1 year, 88% of these patients achieved low disease activity (a 28-joint Disease Activity Score [DAS28] less than 3.2), compared with 18% assigned to biologic therapy (P = .006).

Patients with a high score on Vectra DA were more likely to respond to biologics. In this group, at 1 year, low disease activity was achieved in 58% of patients randomized to biologics versus 35% randomized to triple therapy (P = .04).

“At 1 year, the Vectra DA score at 3 months was a superior predictor of response to both conventional triple therapy and biologic therapy, compared with C-reactive protein, erythrocyte sedimentation rate, and DAS28,” Ms. Bolce said.

“These findings may help facilitate and improve the development of individualized and cost-effective treatment plans for individuals with RA,” Ms. Bolce said.

Tapering therapy

A second study analyzed the role of multibiomarker disease activity (Vectra DA score) in predicting relapses in RA patients in sustained remission when tapering disease-modifying antirheumatic drug therapy in the context of the RETRO randomized clinical trial.

On a scale from 0-100, Vectra DA scores of less than 30 are categorized as low, scores 30-44 are called moderate, and those greater than 44 are considered high. Scores were calculated and compared between 94 patients who were relapsing or in sustained remission while tapering DMARD therapy.

Patients were randomized to one of three arms: continuation of DMARD; reduction of DMARD by 50%; or reduction of DMARD by 50% for 6 months and then stopping therapy.

Moderate to high scores were found in one-third of RA patients in remission. Scores were twice as high in relapsing patients (58.3%), compared with those in stable remission (25%). Baseline scores were significantly higher in relapsing patients than in those in stable remission in the entire population, in tapering patients, and in those who stopped DMARDs.

A multivariate analysis found that Vectra DA scores were independent predictors of relapse next to anticitrullinated protein antibody (ACPA) status. Relapse rates were as follows: 13% in VECTRA-low/ACPA-low patients; about one-third in patients positive on one or the other test; and 76.4% in those with high VECTRA DA scores and high ACPA level.

“Vectra DA score improved the prediction of relapses in RA patients in stable remission undergoing DMARD tapering. Combined with ACPA testing, the score allowed a correct identification of relapse in more than 80% of patients,” stated lead author Dr. Juergen Rech of the University of Erlangen-Nuremberg, Germany.

SAN FRANCISCO – Vectra DA, a multibiomarker blood test, can predict response to therapy for patients with rheumatoid arthritis, and it can also identify patients who can safely taper and discontinue disease-modifying antirheumatic drug (DMARD) therapy, according to two separate poster presentations at the annual meeting of the American College of Rheumatology.

Management of patients with RA is typically based on clinical criteria and lab test results. Vectra DA is the only multibiomarker panel available for assessing therapeutic response in RA. The test is Medicare-approved, and Medicare allows about $580 per test, according to a spokesperson for Crescendo Bioscience, the company providing the test. Currently, Vectra DA is used in about 20% of RA patients who are actively managed by a rheumatologist in the United States, and about 40% of U.S. rheumatologists use the test at least once per month, the spokesperson said.

Alice Goodman/Frontline Medical News

“Vectra DA can assess the risk of radiographic changes and track therapeutic response. Patients with low to moderate Vectra DA scores have a reduced risk of radiographic progression over the next year,” said a coauthor of the first study, Rebecca J. Bolce, an employee of Crescendo.

Response to subsequent therapy

This retrospective study analyzed multibiomarker disease activity score (that is, Vectra DA) in incomplete responders to 3 months of methotrexate monotherapy to predict response to subsequent triple therapy versus biologic therapies. The patient sample came from the SWEFOT (Swedish Farmacotherapy) study of patients with early RA.

After 3 months of methotrexate therapy, 157 nonresponders were randomized to triple therapy or methotrexate plus infliximab (biologic therapy). At the time of randomization, nonresponders were assessed with Vectra DA. Patients with low Vectra DA scores (that is, less than 30) were successfully treated with triple therapy; at 1 year, 88% of these patients achieved low disease activity (a 28-joint Disease Activity Score [DAS28] less than 3.2), compared with 18% assigned to biologic therapy (P = .006).

Patients with a high score on Vectra DA were more likely to respond to biologics. In this group, at 1 year, low disease activity was achieved in 58% of patients randomized to biologics versus 35% randomized to triple therapy (P = .04).

“At 1 year, the Vectra DA score at 3 months was a superior predictor of response to both conventional triple therapy and biologic therapy, compared with C-reactive protein, erythrocyte sedimentation rate, and DAS28,” Ms. Bolce said.

“These findings may help facilitate and improve the development of individualized and cost-effective treatment plans for individuals with RA,” Ms. Bolce said.

Tapering therapy

A second study analyzed the role of multibiomarker disease activity (Vectra DA score) in predicting relapses in RA patients in sustained remission when tapering disease-modifying antirheumatic drug therapy in the context of the RETRO randomized clinical trial.

On a scale from 0-100, Vectra DA scores of less than 30 are categorized as low, scores 30-44 are called moderate, and those greater than 44 are considered high. Scores were calculated and compared between 94 patients who were relapsing or in sustained remission while tapering DMARD therapy.

Patients were randomized to one of three arms: continuation of DMARD; reduction of DMARD by 50%; or reduction of DMARD by 50% for 6 months and then stopping therapy.

Moderate to high scores were found in one-third of RA patients in remission. Scores were twice as high in relapsing patients (58.3%), compared with those in stable remission (25%). Baseline scores were significantly higher in relapsing patients than in those in stable remission in the entire population, in tapering patients, and in those who stopped DMARDs.

A multivariate analysis found that Vectra DA scores were independent predictors of relapse next to anticitrullinated protein antibody (ACPA) status. Relapse rates were as follows: 13% in VECTRA-low/ACPA-low patients; about one-third in patients positive on one or the other test; and 76.4% in those with high VECTRA DA scores and high ACPA level.

“Vectra DA score improved the prediction of relapses in RA patients in stable remission undergoing DMARD tapering. Combined with ACPA testing, the score allowed a correct identification of relapse in more than 80% of patients,” stated lead author Dr. Juergen Rech of the University of Erlangen-Nuremberg, Germany.

SAN FRANCISCO – Protection against shingles appeared to wane about 5 years after patients with autoimmune diseases received the live herpes zoster vaccine, according to a large retrospective cohort study presented at the annual meeting of the American College of Rheumatology.

In contrast, shingles risk remained fairly constant among unvaccinated patients during 7 years of follow-up, reported Dr. Huifeng Yun of the department of epidemiology at the University of Alabama at Birmingham. “Our findings suggest that patients might benefit from a booster vaccine at some point after initial vaccination, but further research is needed to determine when and if such a strategy is effective at preventing herpes zoster,” she said.

Amy Karon/Frontline Medical News

The long-term Shingles Prevention Study showed that the live herpes zoster vaccine is effective for about a decade among healthy older individuals. But about 90% of zoster cases occur in patients with autoimmune and inflammatory diseases, for whom the duration of vaccine protection has been unclear, Dr. Yun said. “Antiviral medication approved for herpes zoster reduces the severity and duration of symptoms, but may not prevent postherpetic neuralgia,” making vaccine protection a priority, she added.

Dr. Yun and her associates retrospectively analyzed Medicare data for nearly 179,000 patients with autoimmune and inflammatory conditions between 2006 and 2013. About one-third of patients were vaccinated against herpes zoster, and more than 40% had rheumatoid arthritis, nearly one-third had psoriasis, about 20% had inflammatory bowel disease, about 5% had psoriatic arthritis, and about 1% had ankylosing spondylitis. The researchers matched unvaccinated and vaccinated patients in a 2:1 ratio based on calendar year, age, sex, race, disease type, and use of disease-modifying antirheumatic drugs, biologics, and glucocorticoids. They followed patients from 30 days after vaccination – or the corresponding date in the unvaccinated cohort – until death, first episode of herpes zoster, or the end of 2013, whichever came first.

The rates of herpes zoster among vaccinated patients rose from 0.75/100 person-years during the first year after vaccination to 1.25/100 person-years during the seventh year of follow-up, Dr. Yun said. In contrast, zoster rates among unvaccinated patients remained steady, ranging between 1.32 and 1.35 cases per 100 person-years. In an adjusted analysis of data from 2006 through 2012, vaccinated patients had about half the risk of herpes zoster, compared with unvaccinated patients, during year 1 (relative risk, 0.52) and remained significantly less likely to develop shingles until year 6, when the gap in risk between vaccinated and unvaccinated patients essentially closed (RR, 0.92).

“The herpes zoster vaccine was effective for about 5 years, and results of subgroup analyses were consistent with the main analysis,” Dr. Yun concluded. But the Medicare database lacked details on disease severity or lifestyle factors, both of which might have affected the results, she cautioned.

Dr. Yun disclosed a financial relationship with Amgen. The senior author and two coauthors also disclosed relationships with several pharmaceutical companies. Two investigators had no disclosures.

SAN FRANCISCO – Protection against shingles appeared to wane about 5 years after patients with autoimmune diseases received the live herpes zoster vaccine, according to a large retrospective cohort study presented at the annual meeting of the American College of Rheumatology.

In contrast, shingles risk remained fairly constant among unvaccinated patients during 7 years of follow-up, reported Dr. Huifeng Yun of the department of epidemiology at the University of Alabama at Birmingham. “Our findings suggest that patients might benefit from a booster vaccine at some point after initial vaccination, but further research is needed to determine when and if such a strategy is effective at preventing herpes zoster,” she said.

Amy Karon/Frontline Medical News

The long-term Shingles Prevention Study showed that the live herpes zoster vaccine is effective for about a decade among healthy older individuals. But about 90% of zoster cases occur in patients with autoimmune and inflammatory diseases, for whom the duration of vaccine protection has been unclear, Dr. Yun said. “Antiviral medication approved for herpes zoster reduces the severity and duration of symptoms, but may not prevent postherpetic neuralgia,” making vaccine protection a priority, she added.

Dr. Yun and her associates retrospectively analyzed Medicare data for nearly 179,000 patients with autoimmune and inflammatory conditions between 2006 and 2013. About one-third of patients were vaccinated against herpes zoster, and more than 40% had rheumatoid arthritis, nearly one-third had psoriasis, about 20% had inflammatory bowel disease, about 5% had psoriatic arthritis, and about 1% had ankylosing spondylitis. The researchers matched unvaccinated and vaccinated patients in a 2:1 ratio based on calendar year, age, sex, race, disease type, and use of disease-modifying antirheumatic drugs, biologics, and glucocorticoids. They followed patients from 30 days after vaccination – or the corresponding date in the unvaccinated cohort – until death, first episode of herpes zoster, or the end of 2013, whichever came first.

The rates of herpes zoster among vaccinated patients rose from 0.75/100 person-years during the first year after vaccination to 1.25/100 person-years during the seventh year of follow-up, Dr. Yun said. In contrast, zoster rates among unvaccinated patients remained steady, ranging between 1.32 and 1.35 cases per 100 person-years. In an adjusted analysis of data from 2006 through 2012, vaccinated patients had about half the risk of herpes zoster, compared with unvaccinated patients, during year 1 (relative risk, 0.52) and remained significantly less likely to develop shingles until year 6, when the gap in risk between vaccinated and unvaccinated patients essentially closed (RR, 0.92).

“The herpes zoster vaccine was effective for about 5 years, and results of subgroup analyses were consistent with the main analysis,” Dr. Yun concluded. But the Medicare database lacked details on disease severity or lifestyle factors, both of which might have affected the results, she cautioned.

Dr. Yun disclosed a financial relationship with Amgen. The senior author and two coauthors also disclosed relationships with several pharmaceutical companies. Two investigators had no disclosures.

SAN FRANCISCO – Protection against shingles appeared to wane about 5 years after patients with autoimmune diseases received the live herpes zoster vaccine, according to a large retrospective cohort study presented at the annual meeting of the American College of Rheumatology.

In contrast, shingles risk remained fairly constant among unvaccinated patients during 7 years of follow-up, reported Dr. Huifeng Yun of the department of epidemiology at the University of Alabama at Birmingham. “Our findings suggest that patients might benefit from a booster vaccine at some point after initial vaccination, but further research is needed to determine when and if such a strategy is effective at preventing herpes zoster,” she said.

Amy Karon/Frontline Medical News

The long-term Shingles Prevention Study showed that the live herpes zoster vaccine is effective for about a decade among healthy older individuals. But about 90% of zoster cases occur in patients with autoimmune and inflammatory diseases, for whom the duration of vaccine protection has been unclear, Dr. Yun said. “Antiviral medication approved for herpes zoster reduces the severity and duration of symptoms, but may not prevent postherpetic neuralgia,” making vaccine protection a priority, she added.

Dr. Yun and her associates retrospectively analyzed Medicare data for nearly 179,000 patients with autoimmune and inflammatory conditions between 2006 and 2013. About one-third of patients were vaccinated against herpes zoster, and more than 40% had rheumatoid arthritis, nearly one-third had psoriasis, about 20% had inflammatory bowel disease, about 5% had psoriatic arthritis, and about 1% had ankylosing spondylitis. The researchers matched unvaccinated and vaccinated patients in a 2:1 ratio based on calendar year, age, sex, race, disease type, and use of disease-modifying antirheumatic drugs, biologics, and glucocorticoids. They followed patients from 30 days after vaccination – or the corresponding date in the unvaccinated cohort – until death, first episode of herpes zoster, or the end of 2013, whichever came first.

The rates of herpes zoster among vaccinated patients rose from 0.75/100 person-years during the first year after vaccination to 1.25/100 person-years during the seventh year of follow-up, Dr. Yun said. In contrast, zoster rates among unvaccinated patients remained steady, ranging between 1.32 and 1.35 cases per 100 person-years. In an adjusted analysis of data from 2006 through 2012, vaccinated patients had about half the risk of herpes zoster, compared with unvaccinated patients, during year 1 (relative risk, 0.52) and remained significantly less likely to develop shingles until year 6, when the gap in risk between vaccinated and unvaccinated patients essentially closed (RR, 0.92).

“The herpes zoster vaccine was effective for about 5 years, and results of subgroup analyses were consistent with the main analysis,” Dr. Yun concluded. But the Medicare database lacked details on disease severity or lifestyle factors, both of which might have affected the results, she cautioned.

Dr. Yun disclosed a financial relationship with Amgen. The senior author and two coauthors also disclosed relationships with several pharmaceutical companies. Two investigators had no disclosures.

SAN FRANCISCO – Two population-based studies provide encouraging evidence that mortality, particularly cardiovascular mortality, is declining in people with rheumatoid arthritis.

The first study – conducted in British Columbia – showed that people diagnosed with rheumatoid arthritis (RA) during 2001-2006 had a lower risk of death, compared with the general population, than did those diagnosed during 1996-2000. The second study focused on cardiovascular death and also found declining death rates in people diagnosed with RA since 2000, compared with RA patients in previous decades.

Both studies suggest that improved detection and management of RA and improved vigilance in screening and managing cardiovascular disease risk factors have contributed to this decline. The studies were presented at the annual meeting of the American College of Rheumatology.

Canadian study

“The take-home message from our study is that with improved treatments and better ability to control inflammation in patients with RA, we are closing the mortality gap between RA patients and the general population. This is a reassuring message for patients and clinicians,” said lead investigator Dr. Diane Lacaille of the University of British Columbia, Vancouver.

It has been recognized for decades that risk of death is higher in people with RA than in the general population, mainly due to an increased risk of cardiovascular disease and cardiovascular death, she noted.

“We have improved RA therapies to attack inflammation, and cardiovascular disease is also linked to inflammation, so we would expect improved mortality along with better treatments,” she continued.

The study compared two cohorts of RA patients with age- and gender-matched controls from the general population: early, those diagnosed with RA during 1996-2000, and late, those diagnosed during 2001-2006. All study subjects were followed from the onset of RA until death or for 5 years.

The entire RA cohort included almost 25,000 people, two thirds of them women, with a mean age of onset of 57 years.

Over the entire 10 years, there was about a 30% increased risk of death from cardiovascular disease, cancer, and infections in people with RA. The mortality was 24.43 per 1,000 person-years in RA participants versus 18.77 deaths per 1,000 person-years in controls, respectively.

When the late cohort of RA patients and controls were compared, the risk of death improved over time, whereas this was not the case in the early cohort. In the early cohort, there was a 64% increase in all-cause mortality, compared with controls. In the late cohort, there was no significant increase in risk of death in RA patients, compared with controls.

RA patients had a 66% increase in cardiovascular disease deaths when compared against controls in the early cohort, but there was no statistically significant increase in the comparison for the late cohort.

Overall, comparisons against controls showed that mortality in the late cohort improved significantly for cardiovascular disease and cancer, but not for infection. Dr. Lacaille speculated that there were too few cases of death due to infection to achieve significance.

“I should caution you that follow-up of 5 years is too short to conclude that there is no increased risk, but we can say that the gap is narrowing,” Dr. Lacaille concluded.

Focus on cardiovascular death

A second study looked for trends among 315 people diagnosed with RA during 2000-2007, 498 people diagnosed with RA in earlier years, and 813 controls without the disease. Participants were followed until death, or until they moved out of the region, or Jan. 1, 2014. These investigators found a decline since 2000 in cardiovascular deaths in people with RA, compared with RA patients in earlier years and controls.

“The implications of our study appear to be broad, that is, there is a beneficial trend in cardiovascular death rates in recent years. We don’t know for sure what factors are causative, but we can assume that improved and more aggressive screening and treatment, as well as being more vigilant about the management of cardiovascular disease in our patients might play a role. This study represents an important step forward and potentially the dawn of a new era in cardiovascular disease management in patients with RA,” said lead investigator Dr. Elena Myasoedova of the Mayo Clinic in Rochester, Minn.

“Although the link between RA and cardiovascular disease is well established, the trends in recent years are not well characterized. We aimed to address this in our study,” she explained.

The database included adult patients older than 18 years diagnosed with incident RA during 2000-2007 and patients diagnosed with RA in the 1990s. RA diagnosis was based on 1997 ACR criteria.

They found a 57% decrease in the overall cardiovascular death rate in patients with RA onset in 2000-2007, compared with the earlier RA cohort. The improvement in deaths from myocardial infarction (coronary heart disease deaths) was particularly striking – an 80% decline in the most recent cohort versus the earlier cohort. Furthermore, the 10-year overall cardiovascular mortality and coronary heart disease mortality in those diagnosed during 2000-2007 did not differ from that of non-RA subjects, which was not observed in RA patients diagnosed in prior decades.

“We observed that cardiovascular disease deaths in patients with recent onset RA is now similar to that of the general population. This suggests that the gap in cardiovascular disease is closing, which has not been reported before,” she stated.

Both investigators emphasized the importance of screening RA patients for cardiovascular morbidity and for managing cardiovascular risk factors.

Dr. Lacaille and Dr. Myasoedova had no financial disclosures. Dr. Myasoedova’s study was supported by a grant from the National Institutes of Health.

rhnews@frontlinemedcom.com

SAN FRANCISCO – Two population-based studies provide encouraging evidence that mortality, particularly cardiovascular mortality, is declining in people with rheumatoid arthritis.

The first study – conducted in British Columbia – showed that people diagnosed with rheumatoid arthritis (RA) during 2001-2006 had a lower risk of death, compared with the general population, than did those diagnosed during 1996-2000. The second study focused on cardiovascular death and also found declining death rates in people diagnosed with RA since 2000, compared with RA patients in previous decades.

Both studies suggest that improved detection and management of RA and improved vigilance in screening and managing cardiovascular disease risk factors have contributed to this decline. The studies were presented at the annual meeting of the American College of Rheumatology.

Canadian study

“The take-home message from our study is that with improved treatments and better ability to control inflammation in patients with RA, we are closing the mortality gap between RA patients and the general population. This is a reassuring message for patients and clinicians,” said lead investigator Dr. Diane Lacaille of the University of British Columbia, Vancouver.

It has been recognized for decades that risk of death is higher in people with RA than in the general population, mainly due to an increased risk of cardiovascular disease and cardiovascular death, she noted.

“We have improved RA therapies to attack inflammation, and cardiovascular disease is also linked to inflammation, so we would expect improved mortality along with better treatments,” she continued.

The study compared two cohorts of RA patients with age- and gender-matched controls from the general population: early, those diagnosed with RA during 1996-2000, and late, those diagnosed during 2001-2006. All study subjects were followed from the onset of RA until death or for 5 years.

The entire RA cohort included almost 25,000 people, two thirds of them women, with a mean age of onset of 57 years.

Over the entire 10 years, there was about a 30% increased risk of death from cardiovascular disease, cancer, and infections in people with RA. The mortality was 24.43 per 1,000 person-years in RA participants versus 18.77 deaths per 1,000 person-years in controls, respectively.

When the late cohort of RA patients and controls were compared, the risk of death improved over time, whereas this was not the case in the early cohort. In the early cohort, there was a 64% increase in all-cause mortality, compared with controls. In the late cohort, there was no significant increase in risk of death in RA patients, compared with controls.

RA patients had a 66% increase in cardiovascular disease deaths when compared against controls in the early cohort, but there was no statistically significant increase in the comparison for the late cohort.

Overall, comparisons against controls showed that mortality in the late cohort improved significantly for cardiovascular disease and cancer, but not for infection. Dr. Lacaille speculated that there were too few cases of death due to infection to achieve significance.

“I should caution you that follow-up of 5 years is too short to conclude that there is no increased risk, but we can say that the gap is narrowing,” Dr. Lacaille concluded.

Focus on cardiovascular death

A second study looked for trends among 315 people diagnosed with RA during 2000-2007, 498 people diagnosed with RA in earlier years, and 813 controls without the disease. Participants were followed until death, or until they moved out of the region, or Jan. 1, 2014. These investigators found a decline since 2000 in cardiovascular deaths in people with RA, compared with RA patients in earlier years and controls.

“The implications of our study appear to be broad, that is, there is a beneficial trend in cardiovascular death rates in recent years. We don’t know for sure what factors are causative, but we can assume that improved and more aggressive screening and treatment, as well as being more vigilant about the management of cardiovascular disease in our patients might play a role. This study represents an important step forward and potentially the dawn of a new era in cardiovascular disease management in patients with RA,” said lead investigator Dr. Elena Myasoedova of the Mayo Clinic in Rochester, Minn.

“Although the link between RA and cardiovascular disease is well established, the trends in recent years are not well characterized. We aimed to address this in our study,” she explained.

The database included adult patients older than 18 years diagnosed with incident RA during 2000-2007 and patients diagnosed with RA in the 1990s. RA diagnosis was based on 1997 ACR criteria.

They found a 57% decrease in the overall cardiovascular death rate in patients with RA onset in 2000-2007, compared with the earlier RA cohort. The improvement in deaths from myocardial infarction (coronary heart disease deaths) was particularly striking – an 80% decline in the most recent cohort versus the earlier cohort. Furthermore, the 10-year overall cardiovascular mortality and coronary heart disease mortality in those diagnosed during 2000-2007 did not differ from that of non-RA subjects, which was not observed in RA patients diagnosed in prior decades.

“We observed that cardiovascular disease deaths in patients with recent onset RA is now similar to that of the general population. This suggests that the gap in cardiovascular disease is closing, which has not been reported before,” she stated.

Both investigators emphasized the importance of screening RA patients for cardiovascular morbidity and for managing cardiovascular risk factors.

Dr. Lacaille and Dr. Myasoedova had no financial disclosures. Dr. Myasoedova’s study was supported by a grant from the National Institutes of Health.

rhnews@frontlinemedcom.com

SAN FRANCISCO – Two population-based studies provide encouraging evidence that mortality, particularly cardiovascular mortality, is declining in people with rheumatoid arthritis.

The first study – conducted in British Columbia – showed that people diagnosed with rheumatoid arthritis (RA) during 2001-2006 had a lower risk of death, compared with the general population, than did those diagnosed during 1996-2000. The second study focused on cardiovascular death and also found declining death rates in people diagnosed with RA since 2000, compared with RA patients in previous decades.

Both studies suggest that improved detection and management of RA and improved vigilance in screening and managing cardiovascular disease risk factors have contributed to this decline. The studies were presented at the annual meeting of the American College of Rheumatology.

Canadian study

“The take-home message from our study is that with improved treatments and better ability to control inflammation in patients with RA, we are closing the mortality gap between RA patients and the general population. This is a reassuring message for patients and clinicians,” said lead investigator Dr. Diane Lacaille of the University of British Columbia, Vancouver.

It has been recognized for decades that risk of death is higher in people with RA than in the general population, mainly due to an increased risk of cardiovascular disease and cardiovascular death, she noted.

“We have improved RA therapies to attack inflammation, and cardiovascular disease is also linked to inflammation, so we would expect improved mortality along with better treatments,” she continued.

The study compared two cohorts of RA patients with age- and gender-matched controls from the general population: early, those diagnosed with RA during 1996-2000, and late, those diagnosed during 2001-2006. All study subjects were followed from the onset of RA until death or for 5 years.

The entire RA cohort included almost 25,000 people, two thirds of them women, with a mean age of onset of 57 years.

Over the entire 10 years, there was about a 30% increased risk of death from cardiovascular disease, cancer, and infections in people with RA. The mortality was 24.43 per 1,000 person-years in RA participants versus 18.77 deaths per 1,000 person-years in controls, respectively.

When the late cohort of RA patients and controls were compared, the risk of death improved over time, whereas this was not the case in the early cohort. In the early cohort, there was a 64% increase in all-cause mortality, compared with controls. In the late cohort, there was no significant increase in risk of death in RA patients, compared with controls.

RA patients had a 66% increase in cardiovascular disease deaths when compared against controls in the early cohort, but there was no statistically significant increase in the comparison for the late cohort.

Overall, comparisons against controls showed that mortality in the late cohort improved significantly for cardiovascular disease and cancer, but not for infection. Dr. Lacaille speculated that there were too few cases of death due to infection to achieve significance.

“I should caution you that follow-up of 5 years is too short to conclude that there is no increased risk, but we can say that the gap is narrowing,” Dr. Lacaille concluded.

Focus on cardiovascular death

A second study looked for trends among 315 people diagnosed with RA during 2000-2007, 498 people diagnosed with RA in earlier years, and 813 controls without the disease. Participants were followed until death, or until they moved out of the region, or Jan. 1, 2014. These investigators found a decline since 2000 in cardiovascular deaths in people with RA, compared with RA patients in earlier years and controls.

“The implications of our study appear to be broad, that is, there is a beneficial trend in cardiovascular death rates in recent years. We don’t know for sure what factors are causative, but we can assume that improved and more aggressive screening and treatment, as well as being more vigilant about the management of cardiovascular disease in our patients might play a role. This study represents an important step forward and potentially the dawn of a new era in cardiovascular disease management in patients with RA,” said lead investigator Dr. Elena Myasoedova of the Mayo Clinic in Rochester, Minn.

“Although the link between RA and cardiovascular disease is well established, the trends in recent years are not well characterized. We aimed to address this in our study,” she explained.

The database included adult patients older than 18 years diagnosed with incident RA during 2000-2007 and patients diagnosed with RA in the 1990s. RA diagnosis was based on 1997 ACR criteria.

They found a 57% decrease in the overall cardiovascular death rate in patients with RA onset in 2000-2007, compared with the earlier RA cohort. The improvement in deaths from myocardial infarction (coronary heart disease deaths) was particularly striking – an 80% decline in the most recent cohort versus the earlier cohort. Furthermore, the 10-year overall cardiovascular mortality and coronary heart disease mortality in those diagnosed during 2000-2007 did not differ from that of non-RA subjects, which was not observed in RA patients diagnosed in prior decades.

“We observed that cardiovascular disease deaths in patients with recent onset RA is now similar to that of the general population. This suggests that the gap in cardiovascular disease is closing, which has not been reported before,” she stated.

Both investigators emphasized the importance of screening RA patients for cardiovascular morbidity and for managing cardiovascular risk factors.

Dr. Lacaille and Dr. Myasoedova had no financial disclosures. Dr. Myasoedova’s study was supported by a grant from the National Institutes of Health.

rhnews@frontlinemedcom.com

San Francisco – Should you give rheumatoid arthritis patients tumor necrosis factor blockers during pregnancy? What can you substitute for methotrexate?

And what in the world do you do about breast feeding?

“The management of rheumatoid arthritis in pregnancy seems to be evolving,” explained Dr. Megan Clowse, a specialist in rheumatology and pregnancy at Duke University, Durham, N.C. “The old strategy of just stopping all the medications and letting the woman flare and using some prednisone really doesn’t seem to actually be achieving the outcomes that we need to get.”

Dr. Clowse answered a host of pregnancy-related questions and more in a pearl-filled interview at the annual meeting of the American College of Rheumatology.

aotto@frontlinemedcom.com

San Francisco – Should you give rheumatoid arthritis patients tumor necrosis factor blockers during pregnancy? What can you substitute for methotrexate?

And what in the world do you do about breast feeding?

“The management of rheumatoid arthritis in pregnancy seems to be evolving,” explained Dr. Megan Clowse, a specialist in rheumatology and pregnancy at Duke University, Durham, N.C. “The old strategy of just stopping all the medications and letting the woman flare and using some prednisone really doesn’t seem to actually be achieving the outcomes that we need to get.”

Dr. Clowse answered a host of pregnancy-related questions and more in a pearl-filled interview at the annual meeting of the American College of Rheumatology.

aotto@frontlinemedcom.com

San Francisco – Should you give rheumatoid arthritis patients tumor necrosis factor blockers during pregnancy? What can you substitute for methotrexate?

And what in the world do you do about breast feeding?

“The management of rheumatoid arthritis in pregnancy seems to be evolving,” explained Dr. Megan Clowse, a specialist in rheumatology and pregnancy at Duke University, Durham, N.C. “The old strategy of just stopping all the medications and letting the woman flare and using some prednisone really doesn’t seem to actually be achieving the outcomes that we need to get.”

Dr. Clowse answered a host of pregnancy-related questions and more in a pearl-filled interview at the annual meeting of the American College of Rheumatology.

aotto@frontlinemedcom.com

SAN FRANCISCO – Rheumatoid arthritis patients who did not respond to the first tumor necrosis factor inhibitor they tried had a higher rate of good or moderate response when they switched to a non–TNF inhibitor biologic, rather than another anti-TNF agent, after 48 weeks in the first randomized trial to compare the two strategies.

The results of this French open-label study, called Rotation or Change, provides evidence to guide the choice of a second biologic in patients who fail first biologic treatment with an anti-TNF agent. The trial also confirms findings reported in observational registry studies, principal investigator Dr. Jacques-Eric Gottenberg said in an interview at the annual meeting of the American College of Rheumatology.

But in contrast to the main study results, a post hoc analysis suggested that a second TNF inhibitor may be just as effective as a non–TNF inhibitor biologic in patients who develop antidrug antibodies to the first TNF inhibitor, said Dr. Gottenberg of the department of rheumatology at Strasbourg (France) University Hospital.

He and his colleagues aimed to mimic what happens in daily practice by allowing participating rheumatologists at French academic medical centers to choose which drug each patient received after randomization. During 2009-2012, 292 patients were randomized to any of four TNF inhibitors (adalimumab, certolizumab pegol, etanercept, or infliximab) or any of three non–TNF inhibitor biologics (abatacept, rituximab, or tocilizumab). (Golimumab was not available in France when the trial began in 2009.)

At 12 weeks, 48% of participants who switched to another TNF inhibitor had good or moderate responses based on European League Against Rheumatism criteria, and this rose to 52% at 24 weeks and then dropped to 43% at 48 weeks. At those time points, good or moderate response occurred in an additional 16%-18% of participants who switched to a non–TNF inhibitor biologic: 64% at 12 weeks, 70% at 24 weeks, and 60% at 48 weeks.

In the post hoc analysis of 278 patients who were tested for antidrug antibodies, 20 patients with ADAs who had been randomized to a non–TNF targeted biologic had a response at 24 weeks that was similar to 12 patients with ADAs who had been randomized to a second TNF inhibitor.

jevans@frontlinemedcom.com

SAN FRANCISCO – Rheumatoid arthritis patients who did not respond to the first tumor necrosis factor inhibitor they tried had a higher rate of good or moderate response when they switched to a non–TNF inhibitor biologic, rather than another anti-TNF agent, after 48 weeks in the first randomized trial to compare the two strategies.

The results of this French open-label study, called Rotation or Change, provides evidence to guide the choice of a second biologic in patients who fail first biologic treatment with an anti-TNF agent. The trial also confirms findings reported in observational registry studies, principal investigator Dr. Jacques-Eric Gottenberg said in an interview at the annual meeting of the American College of Rheumatology.

But in contrast to the main study results, a post hoc analysis suggested that a second TNF inhibitor may be just as effective as a non–TNF inhibitor biologic in patients who develop antidrug antibodies to the first TNF inhibitor, said Dr. Gottenberg of the department of rheumatology at Strasbourg (France) University Hospital.

He and his colleagues aimed to mimic what happens in daily practice by allowing participating rheumatologists at French academic medical centers to choose which drug each patient received after randomization. During 2009-2012, 292 patients were randomized to any of four TNF inhibitors (adalimumab, certolizumab pegol, etanercept, or infliximab) or any of three non–TNF inhibitor biologics (abatacept, rituximab, or tocilizumab). (Golimumab was not available in France when the trial began in 2009.)

At 12 weeks, 48% of participants who switched to another TNF inhibitor had good or moderate responses based on European League Against Rheumatism criteria, and this rose to 52% at 24 weeks and then dropped to 43% at 48 weeks. At those time points, good or moderate response occurred in an additional 16%-18% of participants who switched to a non–TNF inhibitor biologic: 64% at 12 weeks, 70% at 24 weeks, and 60% at 48 weeks.

In the post hoc analysis of 278 patients who were tested for antidrug antibodies, 20 patients with ADAs who had been randomized to a non–TNF targeted biologic had a response at 24 weeks that was similar to 12 patients with ADAs who had been randomized to a second TNF inhibitor.

jevans@frontlinemedcom.com

SAN FRANCISCO – Rheumatoid arthritis patients who did not respond to the first tumor necrosis factor inhibitor they tried had a higher rate of good or moderate response when they switched to a non–TNF inhibitor biologic, rather than another anti-TNF agent, after 48 weeks in the first randomized trial to compare the two strategies.

The results of this French open-label study, called Rotation or Change, provides evidence to guide the choice of a second biologic in patients who fail first biologic treatment with an anti-TNF agent. The trial also confirms findings reported in observational registry studies, principal investigator Dr. Jacques-Eric Gottenberg said in an interview at the annual meeting of the American College of Rheumatology.

But in contrast to the main study results, a post hoc analysis suggested that a second TNF inhibitor may be just as effective as a non–TNF inhibitor biologic in patients who develop antidrug antibodies to the first TNF inhibitor, said Dr. Gottenberg of the department of rheumatology at Strasbourg (France) University Hospital.

He and his colleagues aimed to mimic what happens in daily practice by allowing participating rheumatologists at French academic medical centers to choose which drug each patient received after randomization. During 2009-2012, 292 patients were randomized to any of four TNF inhibitors (adalimumab, certolizumab pegol, etanercept, or infliximab) or any of three non–TNF inhibitor biologics (abatacept, rituximab, or tocilizumab). (Golimumab was not available in France when the trial began in 2009.)

At 12 weeks, 48% of participants who switched to another TNF inhibitor had good or moderate responses based on European League Against Rheumatism criteria, and this rose to 52% at 24 weeks and then dropped to 43% at 48 weeks. At those time points, good or moderate response occurred in an additional 16%-18% of participants who switched to a non–TNF inhibitor biologic: 64% at 12 weeks, 70% at 24 weeks, and 60% at 48 weeks.

In the post hoc analysis of 278 patients who were tested for antidrug antibodies, 20 patients with ADAs who had been randomized to a non–TNF targeted biologic had a response at 24 weeks that was similar to 12 patients with ADAs who had been randomized to a second TNF inhibitor.

jevans@frontlinemedcom.com