ACR Annual Meeting 2015

SAN FRANCISCO – A variety of new, repurposed, and reformulated compounds have made their way into clinical trials for systemic lupus erythematosus, as evidenced by an abstracts session devoted to them at the annual meeting of the American College of Rheumatology. The drugs undergoing testing include a subcutaneous formulation of belimumab, anifrolumab, dapirolizumab pegol, arsenic trioxide, and low-dose interleukin-2.

Some of the approaches have a longer track record, and are at the phase III stage of evaluation. One such molecule is belimumab (Benlysta), a recombinant human monoclonal antibody targeted to B-lymphocyte stimulator. It is approved as an intravenous formulation for treating adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy, but is being tested as a self-administered subcutaneous injection.

“Self-administration of subcutaneous (SC) belimumab will enhance treatment options for patients with SLE,” commented Dr. William Stohl of the University of Southern California, Los Angeles. He and his colleagues explored the potential of SC belimumab in a double-blind, placebo-controlled, 52-week BLISSFUL trial in which all SLE patients received standard of care and were randomized to weekly placebo SC injections (n = 280) or belimumab 200 mg SC weekly (n = 556) across 177 sites in 30 countries. The trial is sponsored by GlaxoSmithKline, which markets belimumab. Belimumab achieved the trial’s primary endpoint, the rate of response on the SLE Responder Index 4 (SRI-4) at week 52 (odds ratio, 1.64; 95% confidence interval, 1.22-2.20; P = .0011) and the key secondary endpoint of time to first severe flare (OR, 0.50; 95% CI, 0.34-0.73; P = .0003). Belimumab treatment reduced steroid use but not to a statistically significant extent (OR, 1.65; 95% CI, 0.95-2.84; P = .0732). The approach was well tolerated.

Another monoclonal antibody of note, anifrolumab, blocks the receptor for type 1 interferon, which has been implicated in SLE pathology. A phase IIb trial funded by MedImmune that involved 305 seropositive patients with moderate to severe SLE who had not responded to prior therapy randomized the patients to intravenous placebo (n = 102) or intravenous anifrolumab at 300 mg (n = 99) or 1,000 mg (n = 104) every 4 weeks for 48 weeks. Significant alterations of serum biomarkers were apparent, which were reflected by the clinical benefits observed. The study arms were comparable at baseline demographically and in SLE clinical characteristics. The primary efficacy endpoint of SRI-4 at day 169 was achieved by 300 mg and 1,000 mg anifrolumab in 34.3% and 28.8% of patients, respectively, compared with 17.6% of those in the placebo arm (P = .014 and .063, respectively). Both doses also achieved the secondary endpoint of SRI-4 at day 365 (51.5% for 300 mg and 38.5% for 1,000 mg), compared with 25.5% in the placebo arm (P less than .001 and P = .048, respectively). Organ-specific measures, the frequency and severity of flares, and disease activity were all beneficially affected by both doses. The adverse event profile and frequency were similar in the study arms. “Patients with active SLE became less active,” commented the study’s principal investigator, Dr. Richard A. Furie of the North Shore–LIJ Health System, New York. “Targeting the [interferon alpha/beta receptor] is a promising therapeutic approach for patients with SLE who do not respond to currently available therapies.”

Other approaches to SLE treatment are more exploratory or represent a repurposing of established drugs. A UCB- and Biogen-sponsored, phase I, double-blind, placebo-controlled study explored the effect of repeated doses of dapirolizumab pegol over 10 weeks, with 28 weeks of follow-up. Dapirolizumab pegol consists of a pegylated, humanized anti-CD40 ligand Fab fragment that lacks the Fc region that has produced thromboembolic complications in earlier studies of monoclonal antibodies to CD40 ligand. In the study, the drug produced no serious treatment-emergent adverse events and no deaths in 14 patients, and showed some initial signs of activity in several measures of clinical response, compared with 7 placebo-treated patients.

The phase I/II proof of concept LUPSENIC trial assessed the safety and efficacy (as a secondary endpoint) of arsenic trioxide as potential treatment for moderate to severe SLE. Arsenic trioxide is approved for the treatment of acute promyelocytic leukemia. The regimen comprised 10 fixed-dose intravenous infusions over 24 days and a 20-week follow-up. “With only 4 weeks of treatment, arsenic trioxide demonstrated an acceptable safety and tolerability profile at 24 weeks with promising short-term clinical efficacy,” said Dr. Mohamed Hamidou of Nantes (France) University Hospital, which sponsored the study along with Medsenic. The results warrant further study, Dr. Hamidou said, with a focus on long-term safety and the value of the approach as a maintenance therapy.

The first trial to examine low-dose interleukin-2 (IL-2) in SLE indicated the value of IL-2 in reestablishing immune homeostasis. A total of 40 SLE patients in the open-label, uncontrolled, prospective study received three courses of SC injections of 1 million IU of IL-2, with a 2-week break between courses. Response to IL-2 was swift and robust as determined by a variety of lab and renal function parameters, and improved clinical characteristics. The immunologic basis for the improvements appears to be an immune modulation involving the selective expansion of regulatory T cells, and selective suppression of follicular and IL-17–producing helper T cells. The Peking University People’s Hospital and Monash University sponsored the study.

Dr. Stohl reported consulting fees from Akros Pharma, Janssen, and GlaxoSmithKline. Dr. Furie has received research grants from MedImmune. Dr. Hamidou had no disclosures.

SAN FRANCISCO – A variety of new, repurposed, and reformulated compounds have made their way into clinical trials for systemic lupus erythematosus, as evidenced by an abstracts session devoted to them at the annual meeting of the American College of Rheumatology. The drugs undergoing testing include a subcutaneous formulation of belimumab, anifrolumab, dapirolizumab pegol, arsenic trioxide, and low-dose interleukin-2.

Some of the approaches have a longer track record, and are at the phase III stage of evaluation. One such molecule is belimumab (Benlysta), a recombinant human monoclonal antibody targeted to B-lymphocyte stimulator. It is approved as an intravenous formulation for treating adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy, but is being tested as a self-administered subcutaneous injection.

“Self-administration of subcutaneous (SC) belimumab will enhance treatment options for patients with SLE,” commented Dr. William Stohl of the University of Southern California, Los Angeles. He and his colleagues explored the potential of SC belimumab in a double-blind, placebo-controlled, 52-week BLISSFUL trial in which all SLE patients received standard of care and were randomized to weekly placebo SC injections (n = 280) or belimumab 200 mg SC weekly (n = 556) across 177 sites in 30 countries. The trial is sponsored by GlaxoSmithKline, which markets belimumab. Belimumab achieved the trial’s primary endpoint, the rate of response on the SLE Responder Index 4 (SRI-4) at week 52 (odds ratio, 1.64; 95% confidence interval, 1.22-2.20; P = .0011) and the key secondary endpoint of time to first severe flare (OR, 0.50; 95% CI, 0.34-0.73; P = .0003). Belimumab treatment reduced steroid use but not to a statistically significant extent (OR, 1.65; 95% CI, 0.95-2.84; P = .0732). The approach was well tolerated.

Another monoclonal antibody of note, anifrolumab, blocks the receptor for type 1 interferon, which has been implicated in SLE pathology. A phase IIb trial funded by MedImmune that involved 305 seropositive patients with moderate to severe SLE who had not responded to prior therapy randomized the patients to intravenous placebo (n = 102) or intravenous anifrolumab at 300 mg (n = 99) or 1,000 mg (n = 104) every 4 weeks for 48 weeks. Significant alterations of serum biomarkers were apparent, which were reflected by the clinical benefits observed. The study arms were comparable at baseline demographically and in SLE clinical characteristics. The primary efficacy endpoint of SRI-4 at day 169 was achieved by 300 mg and 1,000 mg anifrolumab in 34.3% and 28.8% of patients, respectively, compared with 17.6% of those in the placebo arm (P = .014 and .063, respectively). Both doses also achieved the secondary endpoint of SRI-4 at day 365 (51.5% for 300 mg and 38.5% for 1,000 mg), compared with 25.5% in the placebo arm (P less than .001 and P = .048, respectively). Organ-specific measures, the frequency and severity of flares, and disease activity were all beneficially affected by both doses. The adverse event profile and frequency were similar in the study arms. “Patients with active SLE became less active,” commented the study’s principal investigator, Dr. Richard A. Furie of the North Shore–LIJ Health System, New York. “Targeting the [interferon alpha/beta receptor] is a promising therapeutic approach for patients with SLE who do not respond to currently available therapies.”

Other approaches to SLE treatment are more exploratory or represent a repurposing of established drugs. A UCB- and Biogen-sponsored, phase I, double-blind, placebo-controlled study explored the effect of repeated doses of dapirolizumab pegol over 10 weeks, with 28 weeks of follow-up. Dapirolizumab pegol consists of a pegylated, humanized anti-CD40 ligand Fab fragment that lacks the Fc region that has produced thromboembolic complications in earlier studies of monoclonal antibodies to CD40 ligand. In the study, the drug produced no serious treatment-emergent adverse events and no deaths in 14 patients, and showed some initial signs of activity in several measures of clinical response, compared with 7 placebo-treated patients.

The phase I/II proof of concept LUPSENIC trial assessed the safety and efficacy (as a secondary endpoint) of arsenic trioxide as potential treatment for moderate to severe SLE. Arsenic trioxide is approved for the treatment of acute promyelocytic leukemia. The regimen comprised 10 fixed-dose intravenous infusions over 24 days and a 20-week follow-up. “With only 4 weeks of treatment, arsenic trioxide demonstrated an acceptable safety and tolerability profile at 24 weeks with promising short-term clinical efficacy,” said Dr. Mohamed Hamidou of Nantes (France) University Hospital, which sponsored the study along with Medsenic. The results warrant further study, Dr. Hamidou said, with a focus on long-term safety and the value of the approach as a maintenance therapy.

The first trial to examine low-dose interleukin-2 (IL-2) in SLE indicated the value of IL-2 in reestablishing immune homeostasis. A total of 40 SLE patients in the open-label, uncontrolled, prospective study received three courses of SC injections of 1 million IU of IL-2, with a 2-week break between courses. Response to IL-2 was swift and robust as determined by a variety of lab and renal function parameters, and improved clinical characteristics. The immunologic basis for the improvements appears to be an immune modulation involving the selective expansion of regulatory T cells, and selective suppression of follicular and IL-17–producing helper T cells. The Peking University People’s Hospital and Monash University sponsored the study.

Dr. Stohl reported consulting fees from Akros Pharma, Janssen, and GlaxoSmithKline. Dr. Furie has received research grants from MedImmune. Dr. Hamidou had no disclosures.

SAN FRANCISCO – A variety of new, repurposed, and reformulated compounds have made their way into clinical trials for systemic lupus erythematosus, as evidenced by an abstracts session devoted to them at the annual meeting of the American College of Rheumatology. The drugs undergoing testing include a subcutaneous formulation of belimumab, anifrolumab, dapirolizumab pegol, arsenic trioxide, and low-dose interleukin-2.

Some of the approaches have a longer track record, and are at the phase III stage of evaluation. One such molecule is belimumab (Benlysta), a recombinant human monoclonal antibody targeted to B-lymphocyte stimulator. It is approved as an intravenous formulation for treating adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy, but is being tested as a self-administered subcutaneous injection.

“Self-administration of subcutaneous (SC) belimumab will enhance treatment options for patients with SLE,” commented Dr. William Stohl of the University of Southern California, Los Angeles. He and his colleagues explored the potential of SC belimumab in a double-blind, placebo-controlled, 52-week BLISSFUL trial in which all SLE patients received standard of care and were randomized to weekly placebo SC injections (n = 280) or belimumab 200 mg SC weekly (n = 556) across 177 sites in 30 countries. The trial is sponsored by GlaxoSmithKline, which markets belimumab. Belimumab achieved the trial’s primary endpoint, the rate of response on the SLE Responder Index 4 (SRI-4) at week 52 (odds ratio, 1.64; 95% confidence interval, 1.22-2.20; P = .0011) and the key secondary endpoint of time to first severe flare (OR, 0.50; 95% CI, 0.34-0.73; P = .0003). Belimumab treatment reduced steroid use but not to a statistically significant extent (OR, 1.65; 95% CI, 0.95-2.84; P = .0732). The approach was well tolerated.

Another monoclonal antibody of note, anifrolumab, blocks the receptor for type 1 interferon, which has been implicated in SLE pathology. A phase IIb trial funded by MedImmune that involved 305 seropositive patients with moderate to severe SLE who had not responded to prior therapy randomized the patients to intravenous placebo (n = 102) or intravenous anifrolumab at 300 mg (n = 99) or 1,000 mg (n = 104) every 4 weeks for 48 weeks. Significant alterations of serum biomarkers were apparent, which were reflected by the clinical benefits observed. The study arms were comparable at baseline demographically and in SLE clinical characteristics. The primary efficacy endpoint of SRI-4 at day 169 was achieved by 300 mg and 1,000 mg anifrolumab in 34.3% and 28.8% of patients, respectively, compared with 17.6% of those in the placebo arm (P = .014 and .063, respectively). Both doses also achieved the secondary endpoint of SRI-4 at day 365 (51.5% for 300 mg and 38.5% for 1,000 mg), compared with 25.5% in the placebo arm (P less than .001 and P = .048, respectively). Organ-specific measures, the frequency and severity of flares, and disease activity were all beneficially affected by both doses. The adverse event profile and frequency were similar in the study arms. “Patients with active SLE became less active,” commented the study’s principal investigator, Dr. Richard A. Furie of the North Shore–LIJ Health System, New York. “Targeting the [interferon alpha/beta receptor] is a promising therapeutic approach for patients with SLE who do not respond to currently available therapies.”

Other approaches to SLE treatment are more exploratory or represent a repurposing of established drugs. A UCB- and Biogen-sponsored, phase I, double-blind, placebo-controlled study explored the effect of repeated doses of dapirolizumab pegol over 10 weeks, with 28 weeks of follow-up. Dapirolizumab pegol consists of a pegylated, humanized anti-CD40 ligand Fab fragment that lacks the Fc region that has produced thromboembolic complications in earlier studies of monoclonal antibodies to CD40 ligand. In the study, the drug produced no serious treatment-emergent adverse events and no deaths in 14 patients, and showed some initial signs of activity in several measures of clinical response, compared with 7 placebo-treated patients.

The phase I/II proof of concept LUPSENIC trial assessed the safety and efficacy (as a secondary endpoint) of arsenic trioxide as potential treatment for moderate to severe SLE. Arsenic trioxide is approved for the treatment of acute promyelocytic leukemia. The regimen comprised 10 fixed-dose intravenous infusions over 24 days and a 20-week follow-up. “With only 4 weeks of treatment, arsenic trioxide demonstrated an acceptable safety and tolerability profile at 24 weeks with promising short-term clinical efficacy,” said Dr. Mohamed Hamidou of Nantes (France) University Hospital, which sponsored the study along with Medsenic. The results warrant further study, Dr. Hamidou said, with a focus on long-term safety and the value of the approach as a maintenance therapy.

The first trial to examine low-dose interleukin-2 (IL-2) in SLE indicated the value of IL-2 in reestablishing immune homeostasis. A total of 40 SLE patients in the open-label, uncontrolled, prospective study received three courses of SC injections of 1 million IU of IL-2, with a 2-week break between courses. Response to IL-2 was swift and robust as determined by a variety of lab and renal function parameters, and improved clinical characteristics. The immunologic basis for the improvements appears to be an immune modulation involving the selective expansion of regulatory T cells, and selective suppression of follicular and IL-17–producing helper T cells. The Peking University People’s Hospital and Monash University sponsored the study.

Dr. Stohl reported consulting fees from Akros Pharma, Janssen, and GlaxoSmithKline. Dr. Furie has received research grants from MedImmune. Dr. Hamidou had no disclosures.

SAN FRANCISCO – Adalimumab was the clear winner over infliximab and etanercept for anterior uveitis in a Scandinavian database study of 1,365 patients with ankylosing spondylitis.

Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab (Humira). Flares per 100 patient-years dropped by almost 70%.

There was less improvement with infliximab (Remicade), which tended to be used in low doses in the study, less than 5 mg/kg. Office visits dropped from 50.4 to 27.3 per 100 patient-years for the 605 patients who started on it. Flares decreased by about 40%.

Etanercept (Enbrel), meanwhile, seemed to make uveitis worse, a concern that’s been raised previously. Office visits for uveitis increased from 38.1 to 56.5 per 100 patient-years for the 354 patients started on etanercept. Flares increased by about 20%.

The results were presented at the annual meeting of the American College of Rheumatology.

Among patients who were uveitis free in the 2 years prior to starting a tumor necrosis factor inhibitor (TNFi), the risk of flare was far greater with etanercept than with adalimumab (adjusted hazard ratio, 3.69; 95% confidence interval, 1.61-8.46). The risk also was higher for infliximab, though not significantly so (adjusted HR, 1.67; 95% CI, 0.69-4.04).

About 2% of adalimumab patients had their first bout of uveitis after starting it, versus 5.3% of infliximab and 13.7% of etanercept patients.

“A clear reduction in uveitis rates was observed for adalimumab, a slight reduction for infliximab, and a marked increase for etanercept, irrespective of the method for counting flares,” reported Dr. Elisabeth Lie, a rheumatology fellow at Gothenburg (Sweden) University.

In the adjusted analysis, “adalimumab and infliximab were associated with significantly lower hazard for first uveitis flare than etanercept,” noted Dr. Lie.

“Right now, we are still favoring infliximab because it comes as a biosimilar, so it’s inexpensive; I think we are giving it the benefit of the doubt. Still, these results are so favorable for adalimumab” that they make “a strong case to at least have a lower threshold to switch to it if you are not successful with your first choice,” Dr. Lie said in an interview.

The etanercept findings are “at least a reminder that if you have a patient with any history of uveitis, choose another option. I’ve seen a few” cases apparently triggered by etanercept. When that happens, “switch to something else,” she said.

The problem with etanercept may be related to its structure or immunologic effects, but no one really knows for sure, she added.

The study linked the first-time use of a TNFi by ankylosing spondylitis patients in the Swedish Biologics Register to their office visits for anterior uveitis as captured in the country’s National Patient Register. Dr. Lie and her coinvestigators analyzed the 2 years before and after the start of a TNFi. Adalimumab was more frequently used toward the end of the study period, which ran from 2003 through 2010.

Patients were in their early 40s, on average, and almost three-quarters were men. Infliximab patients most often used concomitant disease-modifying antirheumatic drugs and had the highest rate of comorbid inflammatory bowel disease, at 10.4%. Adalimumab patients had the lowest median baseline C-reactive protein at 10 mg/L, but highest pretreatment rate of uveitis, at 28%.

Dr. Lie is a speaker and consultant for AbbVie, the maker of adalimumab, and Pfizer, the maker of etanercept.

aotto@frontlinemedcom.com

SAN FRANCISCO – Adalimumab was the clear winner over infliximab and etanercept for anterior uveitis in a Scandinavian database study of 1,365 patients with ankylosing spondylitis.

Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab (Humira). Flares per 100 patient-years dropped by almost 70%.

There was less improvement with infliximab (Remicade), which tended to be used in low doses in the study, less than 5 mg/kg. Office visits dropped from 50.4 to 27.3 per 100 patient-years for the 605 patients who started on it. Flares decreased by about 40%.

Etanercept (Enbrel), meanwhile, seemed to make uveitis worse, a concern that’s been raised previously. Office visits for uveitis increased from 38.1 to 56.5 per 100 patient-years for the 354 patients started on etanercept. Flares increased by about 20%.

The results were presented at the annual meeting of the American College of Rheumatology.

Among patients who were uveitis free in the 2 years prior to starting a tumor necrosis factor inhibitor (TNFi), the risk of flare was far greater with etanercept than with adalimumab (adjusted hazard ratio, 3.69; 95% confidence interval, 1.61-8.46). The risk also was higher for infliximab, though not significantly so (adjusted HR, 1.67; 95% CI, 0.69-4.04).

About 2% of adalimumab patients had their first bout of uveitis after starting it, versus 5.3% of infliximab and 13.7% of etanercept patients.

“A clear reduction in uveitis rates was observed for adalimumab, a slight reduction for infliximab, and a marked increase for etanercept, irrespective of the method for counting flares,” reported Dr. Elisabeth Lie, a rheumatology fellow at Gothenburg (Sweden) University.

In the adjusted analysis, “adalimumab and infliximab were associated with significantly lower hazard for first uveitis flare than etanercept,” noted Dr. Lie.

“Right now, we are still favoring infliximab because it comes as a biosimilar, so it’s inexpensive; I think we are giving it the benefit of the doubt. Still, these results are so favorable for adalimumab” that they make “a strong case to at least have a lower threshold to switch to it if you are not successful with your first choice,” Dr. Lie said in an interview.

The etanercept findings are “at least a reminder that if you have a patient with any history of uveitis, choose another option. I’ve seen a few” cases apparently triggered by etanercept. When that happens, “switch to something else,” she said.

The problem with etanercept may be related to its structure or immunologic effects, but no one really knows for sure, she added.

The study linked the first-time use of a TNFi by ankylosing spondylitis patients in the Swedish Biologics Register to their office visits for anterior uveitis as captured in the country’s National Patient Register. Dr. Lie and her coinvestigators analyzed the 2 years before and after the start of a TNFi. Adalimumab was more frequently used toward the end of the study period, which ran from 2003 through 2010.

Patients were in their early 40s, on average, and almost three-quarters were men. Infliximab patients most often used concomitant disease-modifying antirheumatic drugs and had the highest rate of comorbid inflammatory bowel disease, at 10.4%. Adalimumab patients had the lowest median baseline C-reactive protein at 10 mg/L, but highest pretreatment rate of uveitis, at 28%.

Dr. Lie is a speaker and consultant for AbbVie, the maker of adalimumab, and Pfizer, the maker of etanercept.

aotto@frontlinemedcom.com

SAN FRANCISCO – Adalimumab was the clear winner over infliximab and etanercept for anterior uveitis in a Scandinavian database study of 1,365 patients with ankylosing spondylitis.

Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab (Humira). Flares per 100 patient-years dropped by almost 70%.

There was less improvement with infliximab (Remicade), which tended to be used in low doses in the study, less than 5 mg/kg. Office visits dropped from 50.4 to 27.3 per 100 patient-years for the 605 patients who started on it. Flares decreased by about 40%.

Etanercept (Enbrel), meanwhile, seemed to make uveitis worse, a concern that’s been raised previously. Office visits for uveitis increased from 38.1 to 56.5 per 100 patient-years for the 354 patients started on etanercept. Flares increased by about 20%.

The results were presented at the annual meeting of the American College of Rheumatology.

Among patients who were uveitis free in the 2 years prior to starting a tumor necrosis factor inhibitor (TNFi), the risk of flare was far greater with etanercept than with adalimumab (adjusted hazard ratio, 3.69; 95% confidence interval, 1.61-8.46). The risk also was higher for infliximab, though not significantly so (adjusted HR, 1.67; 95% CI, 0.69-4.04).

About 2% of adalimumab patients had their first bout of uveitis after starting it, versus 5.3% of infliximab and 13.7% of etanercept patients.

“A clear reduction in uveitis rates was observed for adalimumab, a slight reduction for infliximab, and a marked increase for etanercept, irrespective of the method for counting flares,” reported Dr. Elisabeth Lie, a rheumatology fellow at Gothenburg (Sweden) University.

In the adjusted analysis, “adalimumab and infliximab were associated with significantly lower hazard for first uveitis flare than etanercept,” noted Dr. Lie.

“Right now, we are still favoring infliximab because it comes as a biosimilar, so it’s inexpensive; I think we are giving it the benefit of the doubt. Still, these results are so favorable for adalimumab” that they make “a strong case to at least have a lower threshold to switch to it if you are not successful with your first choice,” Dr. Lie said in an interview.

The etanercept findings are “at least a reminder that if you have a patient with any history of uveitis, choose another option. I’ve seen a few” cases apparently triggered by etanercept. When that happens, “switch to something else,” she said.

The problem with etanercept may be related to its structure or immunologic effects, but no one really knows for sure, she added.

The study linked the first-time use of a TNFi by ankylosing spondylitis patients in the Swedish Biologics Register to their office visits for anterior uveitis as captured in the country’s National Patient Register. Dr. Lie and her coinvestigators analyzed the 2 years before and after the start of a TNFi. Adalimumab was more frequently used toward the end of the study period, which ran from 2003 through 2010.

Patients were in their early 40s, on average, and almost three-quarters were men. Infliximab patients most often used concomitant disease-modifying antirheumatic drugs and had the highest rate of comorbid inflammatory bowel disease, at 10.4%. Adalimumab patients had the lowest median baseline C-reactive protein at 10 mg/L, but highest pretreatment rate of uveitis, at 28%.

Dr. Lie is a speaker and consultant for AbbVie, the maker of adalimumab, and Pfizer, the maker of etanercept.

aotto@frontlinemedcom.com

SAN FRANCISCO – Phase III clinical trial experience in using riociguat indicates that the drug is just as safe and effective in treating pulmonary arterial hypertension associated with connective tissue disease (CTD), particularly systemic sclerosis, as it is for the overall group of patients with PAH caused by various conditions.

“Riociguat [Adempas] slowed deterioration of exercise capacity in patients with scleroderma, with clinical effects sustained over the 2-year follow-up. Long-term safety and tolerability of riociguat in patients with PAH-CTD was quite acceptable and was similar to the overall PATENT population, with no new safety signals,” lead investigator Dr. Christopher P. Denton said at the annual meeting of the American College of Rheumatology.

The phase III, randomized, placebo-controlled PATENT-1 trial demonstrated riociguat’s benefits over 12 weeks, principally the increased exercise capacity in terms of 6-minute walk distance. The open-label extension PATENT-2 trial confirmed the long-term nature of the improvements out to 2 years. The trials were pivotal in securing approval of the novel soluble guanylate cyclase stimulator for treatment of PAH.

PAH-CTD cases comprised 25% of the total PATENT population, second only to patients with idiopathic disease. About half of the PAH-CTD cases were patients with systemic sclerosis (SSc), who typically have an especially poor prognosis. This offered the opportunity to fine-tune the analysis of riociguat’s efficacy and safety to this subgroup.

All PAH-CTD patients had appreciable signs of pulmonary hypertension on physical exertion. Most were already receiving PAH therapy, so any improvements would be on top of already existing treatment-related gains. At week 12 of the PATENT-1 trial, more PAH-CTD patients in the placebo group had died, worsened clinically, or withdrawn than in the riociguat group (24% vs. 8%). Clinical worsening had occurred in 12% of those receiving placebo, compared with none in the riociguat group. The benefits of riociguat in terms of 6-minute walk distance performance and improved World Health Organization functional class were especially pronounced for SSc patients. Analysis of PATENT-2 data demonstrated the durability of the improvements over the 2-year follow-up.

The types and frequencies of adverse events and serious adverse events were similar in PAH-CTD patients and the overall population. “Very reassuringly,” the 2-year survival rate exceeded 90% overall and was 93% in PAH-CTD patients and 94% in PAH patients with SSc, said Dr. Denton of University College London.

“The results are consistent with what is emerging from long-term trials and registry analyses, with an improvement in the longer-term outcome of patients with CTD- and SSc-associated PAH, which is likely a reflection of the more intense approach we are taking in the utility of drugs used in combination to target different pathogenic pathways,” Dr. Denton said.

Dr. Denton reported financial disclosures involving research funding with Actelion, Novartis, Roche, CSL Behring, and Bayer Healthcare. Bayer markets riociguat and sponsored the trials.

SAN FRANCISCO – Phase III clinical trial experience in using riociguat indicates that the drug is just as safe and effective in treating pulmonary arterial hypertension associated with connective tissue disease (CTD), particularly systemic sclerosis, as it is for the overall group of patients with PAH caused by various conditions.

“Riociguat [Adempas] slowed deterioration of exercise capacity in patients with scleroderma, with clinical effects sustained over the 2-year follow-up. Long-term safety and tolerability of riociguat in patients with PAH-CTD was quite acceptable and was similar to the overall PATENT population, with no new safety signals,” lead investigator Dr. Christopher P. Denton said at the annual meeting of the American College of Rheumatology.

The phase III, randomized, placebo-controlled PATENT-1 trial demonstrated riociguat’s benefits over 12 weeks, principally the increased exercise capacity in terms of 6-minute walk distance. The open-label extension PATENT-2 trial confirmed the long-term nature of the improvements out to 2 years. The trials were pivotal in securing approval of the novel soluble guanylate cyclase stimulator for treatment of PAH.

PAH-CTD cases comprised 25% of the total PATENT population, second only to patients with idiopathic disease. About half of the PAH-CTD cases were patients with systemic sclerosis (SSc), who typically have an especially poor prognosis. This offered the opportunity to fine-tune the analysis of riociguat’s efficacy and safety to this subgroup.

All PAH-CTD patients had appreciable signs of pulmonary hypertension on physical exertion. Most were already receiving PAH therapy, so any improvements would be on top of already existing treatment-related gains. At week 12 of the PATENT-1 trial, more PAH-CTD patients in the placebo group had died, worsened clinically, or withdrawn than in the riociguat group (24% vs. 8%). Clinical worsening had occurred in 12% of those receiving placebo, compared with none in the riociguat group. The benefits of riociguat in terms of 6-minute walk distance performance and improved World Health Organization functional class were especially pronounced for SSc patients. Analysis of PATENT-2 data demonstrated the durability of the improvements over the 2-year follow-up.

The types and frequencies of adverse events and serious adverse events were similar in PAH-CTD patients and the overall population. “Very reassuringly,” the 2-year survival rate exceeded 90% overall and was 93% in PAH-CTD patients and 94% in PAH patients with SSc, said Dr. Denton of University College London.

“The results are consistent with what is emerging from long-term trials and registry analyses, with an improvement in the longer-term outcome of patients with CTD- and SSc-associated PAH, which is likely a reflection of the more intense approach we are taking in the utility of drugs used in combination to target different pathogenic pathways,” Dr. Denton said.

Dr. Denton reported financial disclosures involving research funding with Actelion, Novartis, Roche, CSL Behring, and Bayer Healthcare. Bayer markets riociguat and sponsored the trials.

SAN FRANCISCO – Phase III clinical trial experience in using riociguat indicates that the drug is just as safe and effective in treating pulmonary arterial hypertension associated with connective tissue disease (CTD), particularly systemic sclerosis, as it is for the overall group of patients with PAH caused by various conditions.

“Riociguat [Adempas] slowed deterioration of exercise capacity in patients with scleroderma, with clinical effects sustained over the 2-year follow-up. Long-term safety and tolerability of riociguat in patients with PAH-CTD was quite acceptable and was similar to the overall PATENT population, with no new safety signals,” lead investigator Dr. Christopher P. Denton said at the annual meeting of the American College of Rheumatology.

The phase III, randomized, placebo-controlled PATENT-1 trial demonstrated riociguat’s benefits over 12 weeks, principally the increased exercise capacity in terms of 6-minute walk distance. The open-label extension PATENT-2 trial confirmed the long-term nature of the improvements out to 2 years. The trials were pivotal in securing approval of the novel soluble guanylate cyclase stimulator for treatment of PAH.

PAH-CTD cases comprised 25% of the total PATENT population, second only to patients with idiopathic disease. About half of the PAH-CTD cases were patients with systemic sclerosis (SSc), who typically have an especially poor prognosis. This offered the opportunity to fine-tune the analysis of riociguat’s efficacy and safety to this subgroup.

All PAH-CTD patients had appreciable signs of pulmonary hypertension on physical exertion. Most were already receiving PAH therapy, so any improvements would be on top of already existing treatment-related gains. At week 12 of the PATENT-1 trial, more PAH-CTD patients in the placebo group had died, worsened clinically, or withdrawn than in the riociguat group (24% vs. 8%). Clinical worsening had occurred in 12% of those receiving placebo, compared with none in the riociguat group. The benefits of riociguat in terms of 6-minute walk distance performance and improved World Health Organization functional class were especially pronounced for SSc patients. Analysis of PATENT-2 data demonstrated the durability of the improvements over the 2-year follow-up.

The types and frequencies of adverse events and serious adverse events were similar in PAH-CTD patients and the overall population. “Very reassuringly,” the 2-year survival rate exceeded 90% overall and was 93% in PAH-CTD patients and 94% in PAH patients with SSc, said Dr. Denton of University College London.

“The results are consistent with what is emerging from long-term trials and registry analyses, with an improvement in the longer-term outcome of patients with CTD- and SSc-associated PAH, which is likely a reflection of the more intense approach we are taking in the utility of drugs used in combination to target different pathogenic pathways,” Dr. Denton said.

Dr. Denton reported financial disclosures involving research funding with Actelion, Novartis, Roche, CSL Behring, and Bayer Healthcare. Bayer markets riociguat and sponsored the trials.

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.