TBD Meeting (3521-19)

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – The risks of specific manifestations of antiphospholipid syndrome and systemic lupus erythematosus are linked to the types and levels of antiphospholipid antibodies, according to study findings presented at the European Congress of Rheumatology.

Sara Freeman/MDedge News

Spanish researchers found that the number of antiphospholipid (aPL) antibodies present was important for the development of antiphospholipid syndrome (APS) and that lupus anticoagulant (LA) was the major aPL antibody linked to systemic lupus erythematosus (SLE)–related organ involvement.

“aPL [antibodies] has been extensively associated with an increased risk of thrombosis and poor pregnancy outcomes, mainly in patients with primary APS,” study investigator Leyre Riancho-Zarrabeitia, MD, PhD, explained in an interview ahead of the congress.

“Moreover, aPL [antibody] positivity in SLE has been proposed to be associated with higher damage accrual and with certain manifestations such as valvular heart disease, pulmonary hypertension, and neuropsychiatric manifestations,” she added.

Anticardiolipin antibodies – notably IgG rather than IgM isotypes – also seemed to play an important role in APS and SLE manifestations, Dr. Riancho-Zarrabeitia, of Hospital Sierrallana, Instituto De Investigación Marqués De Valdecilla, and the University of Cantabria (Spain), noted during her oral presentation.

She reported data on 3,651 patients included in the RELESSER registry between October 2011 and August 2012. This large, multicenter, hospital-based registry retrospectively collects immunologic, clinical and demographic data from unselected adult patients with SLE who are attending 45 Spanish rheumatology services within the country’s national health system.

Over one-third (37.5%) of patients, who had a mean age of 47 years and were mostly (90%) women, were positive for aPL. The most frequent aPL detected was IgG anticardiolipin (aCL) antibodies, seen in 25% of patients, followed by LA in 24%, and IgM aCL in 20%.

Of the aPL-positive patients, 20.6% were positive for only one antibody, 12.1% were positive for two antibodies, and 4.8% were positive for three antibodies.

“All types of aPL were associated with classic APS manifestations,” Dr. Riancho-Zarrabeitia said. The associations were strongest for thrombotic events, such as arterial and venous small-vessel thrombosis and recurrent early pregnancy losses.

aCL antibodies conferred the highest risk for arterial thrombosis, she noted (odds ratio, 5.7), whereas LA conferred the highest risk for venous thrombosis (OR, 4.7). Both IgG and IgM isotypes were associated with thrombotic events, fetal death and recurrent pregnancy loss, but the association was stronger with the IgG isotypes.

Having more than one aPL was particularly associated with a higher risk of these APS manifestations. For example, when one antibody was present the OR for arterial thrombosis was 4.45, but when two or more aPL were detected, the ORs rose to 9.23 and 15.6, respectively.

aCL and LA also were associated with thrombocytopenia and hemolytic anemia, with ORs of around 1-2 and 2-3 respectively. There also were antibody associations with cognitive impairments.

Similar results were seen in patients with SLE. “aPL [antibody] positivity in SLE patients influenced the risk for thrombotic and obstetric manifestations,” Dr. Riancho-Zarrabeitia said. LA and aCL were associated with an increased risk of neuropsychiatric manifestations, and LA was linked to an increased risk for renal disease.

The risk for specific SLE manifestations was again higher with IgG isotypes of aCL, notably an increased risk for cardiac and respiratory events.

While increased antibody numbers generally led to a higher risk of complications, the risk for cutaneous manifestations decreased.

“The load of aPL [antibodies] confers a higher risk for APS,” Dr. Riancho-Zarrabeitia said during her conclusion. “Regarding systemic lupus erythematosus, the number of positive antibodies is directly associated with neurological and ophthalmological manifestations, and inversely associated with cutaneous manifestations.”

What these findings show, said Dr. Riancho-Zarrabeitia in the precongress interview, is that individuals who test positive for aPL antibodies need careful monitoring to prevent and treat severe manifestations. “The next step would be to confirm our findings with a prospective study.”

Dr. Riancho-Zarrabeitia has received travel grants from AbbVie, Pfizer, UCB, Merck, GlaxoSmithKline, Amgen, and Roche.

SOURCE: Riancho-Zarrabeitia L et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):136-7. Abstract OP0124. doi: 10.1136/annrheumdis-2019-eular.2485.

MADRID – The risks of specific manifestations of antiphospholipid syndrome and systemic lupus erythematosus are linked to the types and levels of antiphospholipid antibodies, according to study findings presented at the European Congress of Rheumatology.

Sara Freeman/MDedge News

Spanish researchers found that the number of antiphospholipid (aPL) antibodies present was important for the development of antiphospholipid syndrome (APS) and that lupus anticoagulant (LA) was the major aPL antibody linked to systemic lupus erythematosus (SLE)–related organ involvement.

“aPL [antibodies] has been extensively associated with an increased risk of thrombosis and poor pregnancy outcomes, mainly in patients with primary APS,” study investigator Leyre Riancho-Zarrabeitia, MD, PhD, explained in an interview ahead of the congress.

“Moreover, aPL [antibody] positivity in SLE has been proposed to be associated with higher damage accrual and with certain manifestations such as valvular heart disease, pulmonary hypertension, and neuropsychiatric manifestations,” she added.

Anticardiolipin antibodies – notably IgG rather than IgM isotypes – also seemed to play an important role in APS and SLE manifestations, Dr. Riancho-Zarrabeitia, of Hospital Sierrallana, Instituto De Investigación Marqués De Valdecilla, and the University of Cantabria (Spain), noted during her oral presentation.

She reported data on 3,651 patients included in the RELESSER registry between October 2011 and August 2012. This large, multicenter, hospital-based registry retrospectively collects immunologic, clinical and demographic data from unselected adult patients with SLE who are attending 45 Spanish rheumatology services within the country’s national health system.

Over one-third (37.5%) of patients, who had a mean age of 47 years and were mostly (90%) women, were positive for aPL. The most frequent aPL detected was IgG anticardiolipin (aCL) antibodies, seen in 25% of patients, followed by LA in 24%, and IgM aCL in 20%.

Of the aPL-positive patients, 20.6% were positive for only one antibody, 12.1% were positive for two antibodies, and 4.8% were positive for three antibodies.

“All types of aPL were associated with classic APS manifestations,” Dr. Riancho-Zarrabeitia said. The associations were strongest for thrombotic events, such as arterial and venous small-vessel thrombosis and recurrent early pregnancy losses.

aCL antibodies conferred the highest risk for arterial thrombosis, she noted (odds ratio, 5.7), whereas LA conferred the highest risk for venous thrombosis (OR, 4.7). Both IgG and IgM isotypes were associated with thrombotic events, fetal death and recurrent pregnancy loss, but the association was stronger with the IgG isotypes.

Having more than one aPL was particularly associated with a higher risk of these APS manifestations. For example, when one antibody was present the OR for arterial thrombosis was 4.45, but when two or more aPL were detected, the ORs rose to 9.23 and 15.6, respectively.

aCL and LA also were associated with thrombocytopenia and hemolytic anemia, with ORs of around 1-2 and 2-3 respectively. There also were antibody associations with cognitive impairments.

Similar results were seen in patients with SLE. “aPL [antibody] positivity in SLE patients influenced the risk for thrombotic and obstetric manifestations,” Dr. Riancho-Zarrabeitia said. LA and aCL were associated with an increased risk of neuropsychiatric manifestations, and LA was linked to an increased risk for renal disease.

The risk for specific SLE manifestations was again higher with IgG isotypes of aCL, notably an increased risk for cardiac and respiratory events.

While increased antibody numbers generally led to a higher risk of complications, the risk for cutaneous manifestations decreased.

“The load of aPL [antibodies] confers a higher risk for APS,” Dr. Riancho-Zarrabeitia said during her conclusion. “Regarding systemic lupus erythematosus, the number of positive antibodies is directly associated with neurological and ophthalmological manifestations, and inversely associated with cutaneous manifestations.”

What these findings show, said Dr. Riancho-Zarrabeitia in the precongress interview, is that individuals who test positive for aPL antibodies need careful monitoring to prevent and treat severe manifestations. “The next step would be to confirm our findings with a prospective study.”

Dr. Riancho-Zarrabeitia has received travel grants from AbbVie, Pfizer, UCB, Merck, GlaxoSmithKline, Amgen, and Roche.

SOURCE: Riancho-Zarrabeitia L et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):136-7. Abstract OP0124. doi: 10.1136/annrheumdis-2019-eular.2485.

MADRID – The risks of specific manifestations of antiphospholipid syndrome and systemic lupus erythematosus are linked to the types and levels of antiphospholipid antibodies, according to study findings presented at the European Congress of Rheumatology.

Sara Freeman/MDedge News

Spanish researchers found that the number of antiphospholipid (aPL) antibodies present was important for the development of antiphospholipid syndrome (APS) and that lupus anticoagulant (LA) was the major aPL antibody linked to systemic lupus erythematosus (SLE)–related organ involvement.

“aPL [antibodies] has been extensively associated with an increased risk of thrombosis and poor pregnancy outcomes, mainly in patients with primary APS,” study investigator Leyre Riancho-Zarrabeitia, MD, PhD, explained in an interview ahead of the congress.

“Moreover, aPL [antibody] positivity in SLE has been proposed to be associated with higher damage accrual and with certain manifestations such as valvular heart disease, pulmonary hypertension, and neuropsychiatric manifestations,” she added.

Anticardiolipin antibodies – notably IgG rather than IgM isotypes – also seemed to play an important role in APS and SLE manifestations, Dr. Riancho-Zarrabeitia, of Hospital Sierrallana, Instituto De Investigación Marqués De Valdecilla, and the University of Cantabria (Spain), noted during her oral presentation.

She reported data on 3,651 patients included in the RELESSER registry between October 2011 and August 2012. This large, multicenter, hospital-based registry retrospectively collects immunologic, clinical and demographic data from unselected adult patients with SLE who are attending 45 Spanish rheumatology services within the country’s national health system.

Over one-third (37.5%) of patients, who had a mean age of 47 years and were mostly (90%) women, were positive for aPL. The most frequent aPL detected was IgG anticardiolipin (aCL) antibodies, seen in 25% of patients, followed by LA in 24%, and IgM aCL in 20%.

Of the aPL-positive patients, 20.6% were positive for only one antibody, 12.1% were positive for two antibodies, and 4.8% were positive for three antibodies.

“All types of aPL were associated with classic APS manifestations,” Dr. Riancho-Zarrabeitia said. The associations were strongest for thrombotic events, such as arterial and venous small-vessel thrombosis and recurrent early pregnancy losses.

aCL antibodies conferred the highest risk for arterial thrombosis, she noted (odds ratio, 5.7), whereas LA conferred the highest risk for venous thrombosis (OR, 4.7). Both IgG and IgM isotypes were associated with thrombotic events, fetal death and recurrent pregnancy loss, but the association was stronger with the IgG isotypes.

Having more than one aPL was particularly associated with a higher risk of these APS manifestations. For example, when one antibody was present the OR for arterial thrombosis was 4.45, but when two or more aPL were detected, the ORs rose to 9.23 and 15.6, respectively.

aCL and LA also were associated with thrombocytopenia and hemolytic anemia, with ORs of around 1-2 and 2-3 respectively. There also were antibody associations with cognitive impairments.

Similar results were seen in patients with SLE. “aPL [antibody] positivity in SLE patients influenced the risk for thrombotic and obstetric manifestations,” Dr. Riancho-Zarrabeitia said. LA and aCL were associated with an increased risk of neuropsychiatric manifestations, and LA was linked to an increased risk for renal disease.

The risk for specific SLE manifestations was again higher with IgG isotypes of aCL, notably an increased risk for cardiac and respiratory events.

While increased antibody numbers generally led to a higher risk of complications, the risk for cutaneous manifestations decreased.

“The load of aPL [antibodies] confers a higher risk for APS,” Dr. Riancho-Zarrabeitia said during her conclusion. “Regarding systemic lupus erythematosus, the number of positive antibodies is directly associated with neurological and ophthalmological manifestations, and inversely associated with cutaneous manifestations.”

What these findings show, said Dr. Riancho-Zarrabeitia in the precongress interview, is that individuals who test positive for aPL antibodies need careful monitoring to prevent and treat severe manifestations. “The next step would be to confirm our findings with a prospective study.”

Dr. Riancho-Zarrabeitia has received travel grants from AbbVie, Pfizer, UCB, Merck, GlaxoSmithKline, Amgen, and Roche.

SOURCE: Riancho-Zarrabeitia L et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):136-7. Abstract OP0124. doi: 10.1136/annrheumdis-2019-eular.2485.

MADRID – Using allopurinol to reduce hyperuricemia in young adults with prehypertension or stage 1 hypertension failed to significantly lower blood pressure but succeeded in significantly improving endothelial function as measured by increased flow-mediated arterial dilation in a single-center crossover study with 82 participants.

The finding of improved endothelial function suggests that reducing hyperuricemia may be a new way to manage hypertension or prevent progression to stage 1 hypertension, improve cardiovascular health, and ultimately cut cardiovascular events, Angelo L. Gaffo, MD, said at the European Congress of Rheumatology. The results indicated that the BP-lowering effect of allopurinol treatment was strongest in people who entered the study with the highest serum urate levels, greater than 6.5 mg/dL, an indication that the next step in developing this approach should be targeting it to people with serum urate levels in this range, said Dr. Gaffo, a rheumatologist at the University of Alabama at Birmingham.

“It’s just a matter of finding the right population to see the blood pressure reduction effect,” Dr. Gaffo said in an interview.

He and his associates designed the SURPHER (Serum Urate Reduction to Prevent Hypertension) study to assess the impact of allopurinol treatment in people aged 18-40 years with prehypertension or stage 1 hypertension as defined by U.S. BP standards at the time they launched the study in 2016 (Contemp Clin Trials. 2016 Sep;50:238-44). Enrolled participants had to be nonsmokers; have an estimated glomerular filtration rate of greater than 60 mL/min per 1.73 m²; have a serum urate level of at least 5.0 mg/dL in men and at least 4.0 mg/dL in women; and be without diabetes, antihypertensive medications, prior urate-lowering treatment, or a history of gout. The 99 people who started the study averaged 28 years old, nearly two-thirds were men, 40% were African Americans, and 52% were white. The participants’ average body mass index was nearly 31 kg/m², and their average BP was 127/81 mm Hg. Average serum urate levels were 6.4 mg/dL in men and 4.9 mg/dL in women. Participants received 300 mg/day allopurinol or placebo, and after 4 weeks crossed to the alternate regimen, with 82 people completing the full protocol. While on allopurinol, serum urate levels fell by an average of 1.3 mg/dL, a statistically significant drop; on placebo, the levels showed no significant change from baseline.

The primary endpoint was the change in BP on allopurinol treatment, which overall showed no statistically significant difference, compared with when participants received placebo. The results also showed no significant impact of allopurinol treatment, compared with placebo, in serum levels of high-sensitivity C-reactive protein, a measure of inflammation. However, for the secondary endpoint of change in endothelial function as measured by a change in flow-mediated dilation (FMD), the results showed a statistically significant effect of allopurinol treatment. While on allopurinol, average FMD increased from 10.3% at baseline to 14.5% on the drug, a 41% relative increase, while on placebo the average FMD rate showed a slight reduction. Allopurinol treatment was safe and well tolerated during the study.

The results also showed that among people with a baseline serum urate level of greater than 6.5 mg/dL (15 of the 82 study completers) systolic BP fell by an average of about 5 mm Hg.

The results suggested that the concept of reducing hyperuricemia in people with early-stage hypertension or prehypertension might be viable for people with higher serum urate levels than most of those enrolled in SURPHER, Dr. Gaffo said. He noted that prior study results in obese adolescents showed that treating hyperuricemia was able to produce a meaningful BP reduction (Hypertension. 2012 Nov;60[5]:1148-56).

SURPHER received no commercial funding. Dr. Gaffo has received research funding from Amgen and AstraZeneca.

mzoler@mdedge.com

MADRID – Using allopurinol to reduce hyperuricemia in young adults with prehypertension or stage 1 hypertension failed to significantly lower blood pressure but succeeded in significantly improving endothelial function as measured by increased flow-mediated arterial dilation in a single-center crossover study with 82 participants.

The finding of improved endothelial function suggests that reducing hyperuricemia may be a new way to manage hypertension or prevent progression to stage 1 hypertension, improve cardiovascular health, and ultimately cut cardiovascular events, Angelo L. Gaffo, MD, said at the European Congress of Rheumatology. The results indicated that the BP-lowering effect of allopurinol treatment was strongest in people who entered the study with the highest serum urate levels, greater than 6.5 mg/dL, an indication that the next step in developing this approach should be targeting it to people with serum urate levels in this range, said Dr. Gaffo, a rheumatologist at the University of Alabama at Birmingham.

“It’s just a matter of finding the right population to see the blood pressure reduction effect,” Dr. Gaffo said in an interview.

He and his associates designed the SURPHER (Serum Urate Reduction to Prevent Hypertension) study to assess the impact of allopurinol treatment in people aged 18-40 years with prehypertension or stage 1 hypertension as defined by U.S. BP standards at the time they launched the study in 2016 (Contemp Clin Trials. 2016 Sep;50:238-44). Enrolled participants had to be nonsmokers; have an estimated glomerular filtration rate of greater than 60 mL/min per 1.73 m²; have a serum urate level of at least 5.0 mg/dL in men and at least 4.0 mg/dL in women; and be without diabetes, antihypertensive medications, prior urate-lowering treatment, or a history of gout. The 99 people who started the study averaged 28 years old, nearly two-thirds were men, 40% were African Americans, and 52% were white. The participants’ average body mass index was nearly 31 kg/m², and their average BP was 127/81 mm Hg. Average serum urate levels were 6.4 mg/dL in men and 4.9 mg/dL in women. Participants received 300 mg/day allopurinol or placebo, and after 4 weeks crossed to the alternate regimen, with 82 people completing the full protocol. While on allopurinol, serum urate levels fell by an average of 1.3 mg/dL, a statistically significant drop; on placebo, the levels showed no significant change from baseline.

The primary endpoint was the change in BP on allopurinol treatment, which overall showed no statistically significant difference, compared with when participants received placebo. The results also showed no significant impact of allopurinol treatment, compared with placebo, in serum levels of high-sensitivity C-reactive protein, a measure of inflammation. However, for the secondary endpoint of change in endothelial function as measured by a change in flow-mediated dilation (FMD), the results showed a statistically significant effect of allopurinol treatment. While on allopurinol, average FMD increased from 10.3% at baseline to 14.5% on the drug, a 41% relative increase, while on placebo the average FMD rate showed a slight reduction. Allopurinol treatment was safe and well tolerated during the study.

The results also showed that among people with a baseline serum urate level of greater than 6.5 mg/dL (15 of the 82 study completers) systolic BP fell by an average of about 5 mm Hg.

The results suggested that the concept of reducing hyperuricemia in people with early-stage hypertension or prehypertension might be viable for people with higher serum urate levels than most of those enrolled in SURPHER, Dr. Gaffo said. He noted that prior study results in obese adolescents showed that treating hyperuricemia was able to produce a meaningful BP reduction (Hypertension. 2012 Nov;60[5]:1148-56).

SURPHER received no commercial funding. Dr. Gaffo has received research funding from Amgen and AstraZeneca.

mzoler@mdedge.com

MADRID – Using allopurinol to reduce hyperuricemia in young adults with prehypertension or stage 1 hypertension failed to significantly lower blood pressure but succeeded in significantly improving endothelial function as measured by increased flow-mediated arterial dilation in a single-center crossover study with 82 participants.

The finding of improved endothelial function suggests that reducing hyperuricemia may be a new way to manage hypertension or prevent progression to stage 1 hypertension, improve cardiovascular health, and ultimately cut cardiovascular events, Angelo L. Gaffo, MD, said at the European Congress of Rheumatology. The results indicated that the BP-lowering effect of allopurinol treatment was strongest in people who entered the study with the highest serum urate levels, greater than 6.5 mg/dL, an indication that the next step in developing this approach should be targeting it to people with serum urate levels in this range, said Dr. Gaffo, a rheumatologist at the University of Alabama at Birmingham.

“It’s just a matter of finding the right population to see the blood pressure reduction effect,” Dr. Gaffo said in an interview.

He and his associates designed the SURPHER (Serum Urate Reduction to Prevent Hypertension) study to assess the impact of allopurinol treatment in people aged 18-40 years with prehypertension or stage 1 hypertension as defined by U.S. BP standards at the time they launched the study in 2016 (Contemp Clin Trials. 2016 Sep;50:238-44). Enrolled participants had to be nonsmokers; have an estimated glomerular filtration rate of greater than 60 mL/min per 1.73 m²; have a serum urate level of at least 5.0 mg/dL in men and at least 4.0 mg/dL in women; and be without diabetes, antihypertensive medications, prior urate-lowering treatment, or a history of gout. The 99 people who started the study averaged 28 years old, nearly two-thirds were men, 40% were African Americans, and 52% were white. The participants’ average body mass index was nearly 31 kg/m², and their average BP was 127/81 mm Hg. Average serum urate levels were 6.4 mg/dL in men and 4.9 mg/dL in women. Participants received 300 mg/day allopurinol or placebo, and after 4 weeks crossed to the alternate regimen, with 82 people completing the full protocol. While on allopurinol, serum urate levels fell by an average of 1.3 mg/dL, a statistically significant drop; on placebo, the levels showed no significant change from baseline.

The primary endpoint was the change in BP on allopurinol treatment, which overall showed no statistically significant difference, compared with when participants received placebo. The results also showed no significant impact of allopurinol treatment, compared with placebo, in serum levels of high-sensitivity C-reactive protein, a measure of inflammation. However, for the secondary endpoint of change in endothelial function as measured by a change in flow-mediated dilation (FMD), the results showed a statistically significant effect of allopurinol treatment. While on allopurinol, average FMD increased from 10.3% at baseline to 14.5% on the drug, a 41% relative increase, while on placebo the average FMD rate showed a slight reduction. Allopurinol treatment was safe and well tolerated during the study.

The results also showed that among people with a baseline serum urate level of greater than 6.5 mg/dL (15 of the 82 study completers) systolic BP fell by an average of about 5 mm Hg.

The results suggested that the concept of reducing hyperuricemia in people with early-stage hypertension or prehypertension might be viable for people with higher serum urate levels than most of those enrolled in SURPHER, Dr. Gaffo said. He noted that prior study results in obese adolescents showed that treating hyperuricemia was able to produce a meaningful BP reduction (Hypertension. 2012 Nov;60[5]:1148-56).

SURPHER received no commercial funding. Dr. Gaffo has received research funding from Amgen and AstraZeneca.

mzoler@mdedge.com

MADRID – An observational study that includes adults and children with cryopyrin-associated periodic syndromes and related diseases has provided real-world evidence that clinical improvement accrues on canakinumab (Ilaris) years after treatment was initiated, according to Norbert Blank, MD, of the division of rheumatology at the University of Heidelberg (Germany).

Summarizing data he presented at the European Congress of Rheumatology, Dr. Blank explained in an interview that the observational study has accrued more than 50 patients so far, with the goal of reaching 300 patients with cryopyrin-associated periodic syndromes and related rare diseases that have responded to anti–interleukin-1 therapy, such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and familial Mediterranean fever.

Most of the patients participating in the observational study, called RELIANCE, were already on canakinumab at the time of enrollment, often for several years. Yet in follow-up so far – which exceeds 1 year for some of the participants – improvement from the time of entry has been seen for some outcomes, such as activity level, according to Dr. Blank.

Canakinumab has been well tolerated with no new or unexpected adverse events emerging in the follow-up so far. Although these data remain limited, Dr. Blank considers them reassuring.

With detailed characterization of these rare diseases at baseline, observational studies like RELIANCE provide valuable real-world data about disease presentation, according to Dr. Blank. He believes that further follow-up will provide a rich source of information about disease course in response to anti-IL-1 therapy, which is being individualized according to response.

MADRID – An observational study that includes adults and children with cryopyrin-associated periodic syndromes and related diseases has provided real-world evidence that clinical improvement accrues on canakinumab (Ilaris) years after treatment was initiated, according to Norbert Blank, MD, of the division of rheumatology at the University of Heidelberg (Germany).

Summarizing data he presented at the European Congress of Rheumatology, Dr. Blank explained in an interview that the observational study has accrued more than 50 patients so far, with the goal of reaching 300 patients with cryopyrin-associated periodic syndromes and related rare diseases that have responded to anti–interleukin-1 therapy, such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and familial Mediterranean fever.

Most of the patients participating in the observational study, called RELIANCE, were already on canakinumab at the time of enrollment, often for several years. Yet in follow-up so far – which exceeds 1 year for some of the participants – improvement from the time of entry has been seen for some outcomes, such as activity level, according to Dr. Blank.

Canakinumab has been well tolerated with no new or unexpected adverse events emerging in the follow-up so far. Although these data remain limited, Dr. Blank considers them reassuring.

With detailed characterization of these rare diseases at baseline, observational studies like RELIANCE provide valuable real-world data about disease presentation, according to Dr. Blank. He believes that further follow-up will provide a rich source of information about disease course in response to anti-IL-1 therapy, which is being individualized according to response.

MADRID – An observational study that includes adults and children with cryopyrin-associated periodic syndromes and related diseases has provided real-world evidence that clinical improvement accrues on canakinumab (Ilaris) years after treatment was initiated, according to Norbert Blank, MD, of the division of rheumatology at the University of Heidelberg (Germany).

Summarizing data he presented at the European Congress of Rheumatology, Dr. Blank explained in an interview that the observational study has accrued more than 50 patients so far, with the goal of reaching 300 patients with cryopyrin-associated periodic syndromes and related rare diseases that have responded to anti–interleukin-1 therapy, such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and familial Mediterranean fever.

Most of the patients participating in the observational study, called RELIANCE, were already on canakinumab at the time of enrollment, often for several years. Yet in follow-up so far – which exceeds 1 year for some of the participants – improvement from the time of entry has been seen for some outcomes, such as activity level, according to Dr. Blank.

Canakinumab has been well tolerated with no new or unexpected adverse events emerging in the follow-up so far. Although these data remain limited, Dr. Blank considers them reassuring.

With detailed characterization of these rare diseases at baseline, observational studies like RELIANCE provide valuable real-world data about disease presentation, according to Dr. Blank. He believes that further follow-up will provide a rich source of information about disease course in response to anti-IL-1 therapy, which is being individualized according to response.

MADRID – The glucagonlike peptide–1 receptor agonist liraglutide appears to be effective for keeping weight off following an intensive weight-loss program in patients with knee osteoarthritis, according to a randomized, double-blind, placebo-controlled trial presented at the European Congress of Rheumatology.

However, even though the 8-week intensive dietary program led to substantial weight loss and significant improvement in pain, additional weight loss of nearly 2.5 kg over 52 weeks of daily liraglutide treatment did not translate into more pain control.

According to study author Lars Erik Kristensen, MD, PhD, this is the first randomized trial to test the ability of liraglutide to provide a sustained weight loss in OA patients. The Food and Drug Administration indication for liraglutide is as an adjunct to diet and exercise for glycemic control in type 2 diabetes mellitus.

The study compared liraglutide against placebo in patients who had completed an intensive weight-control program in which the median loss was 12.46 kg. They were followed for 52 weeks.

At the end of follow-up, patients in the placebo group had gained a mean of 1.17 kg while those randomized to liraglutide lost an additional 2.76 kg. The between-group difference of 3.93 kg was statistically significant (P = .008).

“We believe that liraglutide is a promising agent for sustained weight loss in OA patients,” concluded Dr. Kristensen, a clinical researcher in rheumatology in the Parker Institute at Bispebjerg-Frederiksberg Hospital in Copenhagen.

In the single-center study, 156 patients were enrolled and randomized. In an initial 8-week diet intervention undertaken by both groups, an intensive program for weight loss included average daily calorie intakes of less than 800 kcal along with dietetic counseling. Patients were monitored for daily activities.

The majority of patients achieved a 10% or greater loss of total body weight during the intensive program before initiating 3 mg of once-daily liraglutide or a placebo.

Over the course of 52 weeks, the attrition from the study was relatively low. Among the 80 patients randomized to liraglutide, only 2 were lost because of noncompliance. Another 12 participants left the study before completion, 10 of whom did so for treatment-associated adverse effects. In the placebo arm, four patients were noncompliant, four left for treatment-associated adverse effects, and five left for other reasons.

Following the 8-week intensive dietary program, there was 11.86-point improvement in the pain subscale of the Knee and Osteoarthritis Outcome Score, confirming a substantial symptomatic benefit from this degree of weight loss. While this improvement in pain score was sustained at 52 weeks in both groups, the additional weight loss in the liraglutide arm did not lead to additional pain control.

The lack of additional pain control in the liraglutide group was disappointing, and the reason is unclear, but Dr. Kristensen emphasized that the persistent improvement in pain control was a positive result. In patients who are overweight or obese, regardless of whether they have concomitant OA, weight loss is not only difficult to achieve but difficult to sustain even after a successful intervention.

Dr. Kristensen reported financial relationships with multiple pharmaceutical companies. The trial received funding from Novo Nordisk.

SOURCE: Kristensen LE et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):71-2. Abstract OP0011. doi: 10.1136/annrheumdis-2019-eular.1375.

MADRID – The glucagonlike peptide–1 receptor agonist liraglutide appears to be effective for keeping weight off following an intensive weight-loss program in patients with knee osteoarthritis, according to a randomized, double-blind, placebo-controlled trial presented at the European Congress of Rheumatology.

However, even though the 8-week intensive dietary program led to substantial weight loss and significant improvement in pain, additional weight loss of nearly 2.5 kg over 52 weeks of daily liraglutide treatment did not translate into more pain control.

According to study author Lars Erik Kristensen, MD, PhD, this is the first randomized trial to test the ability of liraglutide to provide a sustained weight loss in OA patients. The Food and Drug Administration indication for liraglutide is as an adjunct to diet and exercise for glycemic control in type 2 diabetes mellitus.

The study compared liraglutide against placebo in patients who had completed an intensive weight-control program in which the median loss was 12.46 kg. They were followed for 52 weeks.

At the end of follow-up, patients in the placebo group had gained a mean of 1.17 kg while those randomized to liraglutide lost an additional 2.76 kg. The between-group difference of 3.93 kg was statistically significant (P = .008).

“We believe that liraglutide is a promising agent for sustained weight loss in OA patients,” concluded Dr. Kristensen, a clinical researcher in rheumatology in the Parker Institute at Bispebjerg-Frederiksberg Hospital in Copenhagen.

In the single-center study, 156 patients were enrolled and randomized. In an initial 8-week diet intervention undertaken by both groups, an intensive program for weight loss included average daily calorie intakes of less than 800 kcal along with dietetic counseling. Patients were monitored for daily activities.

The majority of patients achieved a 10% or greater loss of total body weight during the intensive program before initiating 3 mg of once-daily liraglutide or a placebo.

Over the course of 52 weeks, the attrition from the study was relatively low. Among the 80 patients randomized to liraglutide, only 2 were lost because of noncompliance. Another 12 participants left the study before completion, 10 of whom did so for treatment-associated adverse effects. In the placebo arm, four patients were noncompliant, four left for treatment-associated adverse effects, and five left for other reasons.

Following the 8-week intensive dietary program, there was 11.86-point improvement in the pain subscale of the Knee and Osteoarthritis Outcome Score, confirming a substantial symptomatic benefit from this degree of weight loss. While this improvement in pain score was sustained at 52 weeks in both groups, the additional weight loss in the liraglutide arm did not lead to additional pain control.

The lack of additional pain control in the liraglutide group was disappointing, and the reason is unclear, but Dr. Kristensen emphasized that the persistent improvement in pain control was a positive result. In patients who are overweight or obese, regardless of whether they have concomitant OA, weight loss is not only difficult to achieve but difficult to sustain even after a successful intervention.

Dr. Kristensen reported financial relationships with multiple pharmaceutical companies. The trial received funding from Novo Nordisk.

SOURCE: Kristensen LE et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):71-2. Abstract OP0011. doi: 10.1136/annrheumdis-2019-eular.1375.

MADRID – The glucagonlike peptide–1 receptor agonist liraglutide appears to be effective for keeping weight off following an intensive weight-loss program in patients with knee osteoarthritis, according to a randomized, double-blind, placebo-controlled trial presented at the European Congress of Rheumatology.

However, even though the 8-week intensive dietary program led to substantial weight loss and significant improvement in pain, additional weight loss of nearly 2.5 kg over 52 weeks of daily liraglutide treatment did not translate into more pain control.

According to study author Lars Erik Kristensen, MD, PhD, this is the first randomized trial to test the ability of liraglutide to provide a sustained weight loss in OA patients. The Food and Drug Administration indication for liraglutide is as an adjunct to diet and exercise for glycemic control in type 2 diabetes mellitus.

The study compared liraglutide against placebo in patients who had completed an intensive weight-control program in which the median loss was 12.46 kg. They were followed for 52 weeks.

At the end of follow-up, patients in the placebo group had gained a mean of 1.17 kg while those randomized to liraglutide lost an additional 2.76 kg. The between-group difference of 3.93 kg was statistically significant (P = .008).

“We believe that liraglutide is a promising agent for sustained weight loss in OA patients,” concluded Dr. Kristensen, a clinical researcher in rheumatology in the Parker Institute at Bispebjerg-Frederiksberg Hospital in Copenhagen.

In the single-center study, 156 patients were enrolled and randomized. In an initial 8-week diet intervention undertaken by both groups, an intensive program for weight loss included average daily calorie intakes of less than 800 kcal along with dietetic counseling. Patients were monitored for daily activities.

The majority of patients achieved a 10% or greater loss of total body weight during the intensive program before initiating 3 mg of once-daily liraglutide or a placebo.

Over the course of 52 weeks, the attrition from the study was relatively low. Among the 80 patients randomized to liraglutide, only 2 were lost because of noncompliance. Another 12 participants left the study before completion, 10 of whom did so for treatment-associated adverse effects. In the placebo arm, four patients were noncompliant, four left for treatment-associated adverse effects, and five left for other reasons.

Following the 8-week intensive dietary program, there was 11.86-point improvement in the pain subscale of the Knee and Osteoarthritis Outcome Score, confirming a substantial symptomatic benefit from this degree of weight loss. While this improvement in pain score was sustained at 52 weeks in both groups, the additional weight loss in the liraglutide arm did not lead to additional pain control.

The lack of additional pain control in the liraglutide group was disappointing, and the reason is unclear, but Dr. Kristensen emphasized that the persistent improvement in pain control was a positive result. In patients who are overweight or obese, regardless of whether they have concomitant OA, weight loss is not only difficult to achieve but difficult to sustain even after a successful intervention.

Dr. Kristensen reported financial relationships with multiple pharmaceutical companies. The trial received funding from Novo Nordisk.

SOURCE: Kristensen LE et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):71-2. Abstract OP0011. doi: 10.1136/annrheumdis-2019-eular.1375.

MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).

In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.

As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.


Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.

For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.

In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.

SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.

MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).

In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.

As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.


Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.

For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.

In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.

SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.

MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).

In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.

As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.


Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.

For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.

In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.

SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.

MADRID – Treating patients with axial spondyloarthritis (axSpA) until a specific target is reached is an emerging concept that has gained a lot of traction in the past few years, Pedro Machado, MD, said at the European Congress of Rheumatology.

Vidyard Video

“The availability of biologic therapies has improved the clinical outcomes for our patients with axial spondyloarthritis and targeting clinical remission or inactive disease is now an achievable treatment goal in clinical practice,” he observed. “This has trigged the question: Is there a role for ‘treat-to-target’ in axial spondyloarthritis?”

Dr. Machado, an honorary consultant in rheumatology and muscle diseases at University College Hospital and the National Hospital for Neurology and Neurosurgery in London, took a critical look at the treat-to-target approach during a clinical science session at the meeting, organized by the European League Against Rheumatism (EULAR).

The concept of treat-to-target is not new, he acknowledged, having been imported from other chronic conditions where there is a very specific target to achieve – such as lowering glycated hemoglobin in diabetes or hypertension or hyperlipidemia in cardiovascular disease.

“The concept involves changing or escalating therapy according to a predefined target under the assumption that this may lead to a better outcome compared to what we call ‘routine care,’ ” Dr. Machado explained.

Treat-to-target is not only well established in nonrheumatic diseases but also has proved to work in patients with rheumatoid arthritis and psoriatic arthritis with evidence from the TICORA (Tight Control of Rheumatoid Arthritis) and TICOPA (Tight Control in Psoriatic Arthritis) trials.

Whether the approach can also work in axSpA is open to debate, and one of the main arguments against using a treat-to-target in axSpA asks, what exactly is the target? While there is no firm agreement yet, Dr. Machado observed that achieving either clinical remission or inactive disease would be the most likely target.

It could be argued this is already being done to some degree, but “we need to be more ambitious,” Dr. Machado said. Indeed, current Assessment of Spondyloarthritis International Society/EULAR recommendations for the treatment of axSpA (Ann Rheum Dis. 2017;76[6]:978–91) note when patients with high disease activity despite sufficient standard treatment should be escalated to treatment with a biologic disease-modifying antirheumatic drug (bDMARD). High disease activity was defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or more or a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more.

Another argument against using the approach concerns the evidence base. There are no prospective, randomized trials supporting the use of treat-to-target over routine care. However, there is a lot of observational evidence, Dr. Machado said in an interview. Such studies have shown that achieving inactive disease may improve structural outcomes and stop the development of radiographic damage of the spine. Importantly, these observational studies also show that achieving inactive disease may also help to improve patients’ functional outcomes and quality of life.

Evidence backing a treat-to-target approach in axSpA from a randomized, controlled trial may currently be lacking, but the TiCOSPA (Tight Control in Spondyloarthritis) trial is in progress and should help change that, Dr. Machado said.

“The missing bit is a randomized trial, but I would say that the observational evidence is almost enough to advocate a treat-to-target strategy in axial spondyloarthritis.” This was also the view of an international task force that recently published recommendations and overarching principles for a treat-target strategy in spondyloarthritis, including axSpA (Ann Rheum Dis. 2018;77:3-17).

Of course, a treat-to-target approach may not be without its pitfalls. There are a limited number of drugs currently that could be used to “hit the target” of disease activity, Dr. Machado said in his presentation. The approach might also lead to ‘overtreatment,’ and more treatment is not always better as it could not only lead to more adverse events, but it also may mean the approach is not cost-effective.

Depending on the TiCOSPA study results, which are expected next year, Dr. Machado said that “the feasibility and cost-effectiveness of such a strategy in clinical practice also needs to be tested.”

MADRID – Treating patients with axial spondyloarthritis (axSpA) until a specific target is reached is an emerging concept that has gained a lot of traction in the past few years, Pedro Machado, MD, said at the European Congress of Rheumatology.

Vidyard Video

“The availability of biologic therapies has improved the clinical outcomes for our patients with axial spondyloarthritis and targeting clinical remission or inactive disease is now an achievable treatment goal in clinical practice,” he observed. “This has trigged the question: Is there a role for ‘treat-to-target’ in axial spondyloarthritis?”

Dr. Machado, an honorary consultant in rheumatology and muscle diseases at University College Hospital and the National Hospital for Neurology and Neurosurgery in London, took a critical look at the treat-to-target approach during a clinical science session at the meeting, organized by the European League Against Rheumatism (EULAR).

The concept of treat-to-target is not new, he acknowledged, having been imported from other chronic conditions where there is a very specific target to achieve – such as lowering glycated hemoglobin in diabetes or hypertension or hyperlipidemia in cardiovascular disease.

“The concept involves changing or escalating therapy according to a predefined target under the assumption that this may lead to a better outcome compared to what we call ‘routine care,’ ” Dr. Machado explained.

Treat-to-target is not only well established in nonrheumatic diseases but also has proved to work in patients with rheumatoid arthritis and psoriatic arthritis with evidence from the TICORA (Tight Control of Rheumatoid Arthritis) and TICOPA (Tight Control in Psoriatic Arthritis) trials.

Whether the approach can also work in axSpA is open to debate, and one of the main arguments against using a treat-to-target in axSpA asks, what exactly is the target? While there is no firm agreement yet, Dr. Machado observed that achieving either clinical remission or inactive disease would be the most likely target.

It could be argued this is already being done to some degree, but “we need to be more ambitious,” Dr. Machado said. Indeed, current Assessment of Spondyloarthritis International Society/EULAR recommendations for the treatment of axSpA (Ann Rheum Dis. 2017;76[6]:978–91) note when patients with high disease activity despite sufficient standard treatment should be escalated to treatment with a biologic disease-modifying antirheumatic drug (bDMARD). High disease activity was defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or more or a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more.

Another argument against using the approach concerns the evidence base. There are no prospective, randomized trials supporting the use of treat-to-target over routine care. However, there is a lot of observational evidence, Dr. Machado said in an interview. Such studies have shown that achieving inactive disease may improve structural outcomes and stop the development of radiographic damage of the spine. Importantly, these observational studies also show that achieving inactive disease may also help to improve patients’ functional outcomes and quality of life.

Evidence backing a treat-to-target approach in axSpA from a randomized, controlled trial may currently be lacking, but the TiCOSPA (Tight Control in Spondyloarthritis) trial is in progress and should help change that, Dr. Machado said.

“The missing bit is a randomized trial, but I would say that the observational evidence is almost enough to advocate a treat-to-target strategy in axial spondyloarthritis.” This was also the view of an international task force that recently published recommendations and overarching principles for a treat-target strategy in spondyloarthritis, including axSpA (Ann Rheum Dis. 2018;77:3-17).

Of course, a treat-to-target approach may not be without its pitfalls. There are a limited number of drugs currently that could be used to “hit the target” of disease activity, Dr. Machado said in his presentation. The approach might also lead to ‘overtreatment,’ and more treatment is not always better as it could not only lead to more adverse events, but it also may mean the approach is not cost-effective.

Depending on the TiCOSPA study results, which are expected next year, Dr. Machado said that “the feasibility and cost-effectiveness of such a strategy in clinical practice also needs to be tested.”

MADRID – Treating patients with axial spondyloarthritis (axSpA) until a specific target is reached is an emerging concept that has gained a lot of traction in the past few years, Pedro Machado, MD, said at the European Congress of Rheumatology.

Vidyard Video

“The availability of biologic therapies has improved the clinical outcomes for our patients with axial spondyloarthritis and targeting clinical remission or inactive disease is now an achievable treatment goal in clinical practice,” he observed. “This has trigged the question: Is there a role for ‘treat-to-target’ in axial spondyloarthritis?”

Dr. Machado, an honorary consultant in rheumatology and muscle diseases at University College Hospital and the National Hospital for Neurology and Neurosurgery in London, took a critical look at the treat-to-target approach during a clinical science session at the meeting, organized by the European League Against Rheumatism (EULAR).

The concept of treat-to-target is not new, he acknowledged, having been imported from other chronic conditions where there is a very specific target to achieve – such as lowering glycated hemoglobin in diabetes or hypertension or hyperlipidemia in cardiovascular disease.

“The concept involves changing or escalating therapy according to a predefined target under the assumption that this may lead to a better outcome compared to what we call ‘routine care,’ ” Dr. Machado explained.

Treat-to-target is not only well established in nonrheumatic diseases but also has proved to work in patients with rheumatoid arthritis and psoriatic arthritis with evidence from the TICORA (Tight Control of Rheumatoid Arthritis) and TICOPA (Tight Control in Psoriatic Arthritis) trials.

Whether the approach can also work in axSpA is open to debate, and one of the main arguments against using a treat-to-target in axSpA asks, what exactly is the target? While there is no firm agreement yet, Dr. Machado observed that achieving either clinical remission or inactive disease would be the most likely target.

It could be argued this is already being done to some degree, but “we need to be more ambitious,” Dr. Machado said. Indeed, current Assessment of Spondyloarthritis International Society/EULAR recommendations for the treatment of axSpA (Ann Rheum Dis. 2017;76[6]:978–91) note when patients with high disease activity despite sufficient standard treatment should be escalated to treatment with a biologic disease-modifying antirheumatic drug (bDMARD). High disease activity was defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or more or a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more.

Another argument against using the approach concerns the evidence base. There are no prospective, randomized trials supporting the use of treat-to-target over routine care. However, there is a lot of observational evidence, Dr. Machado said in an interview. Such studies have shown that achieving inactive disease may improve structural outcomes and stop the development of radiographic damage of the spine. Importantly, these observational studies also show that achieving inactive disease may also help to improve patients’ functional outcomes and quality of life.

Evidence backing a treat-to-target approach in axSpA from a randomized, controlled trial may currently be lacking, but the TiCOSPA (Tight Control in Spondyloarthritis) trial is in progress and should help change that, Dr. Machado said.

“The missing bit is a randomized trial, but I would say that the observational evidence is almost enough to advocate a treat-to-target strategy in axial spondyloarthritis.” This was also the view of an international task force that recently published recommendations and overarching principles for a treat-target strategy in spondyloarthritis, including axSpA (Ann Rheum Dis. 2018;77:3-17).

Of course, a treat-to-target approach may not be without its pitfalls. There are a limited number of drugs currently that could be used to “hit the target” of disease activity, Dr. Machado said in his presentation. The approach might also lead to ‘overtreatment,’ and more treatment is not always better as it could not only lead to more adverse events, but it also may mean the approach is not cost-effective.

Depending on the TiCOSPA study results, which are expected next year, Dr. Machado said that “the feasibility and cost-effectiveness of such a strategy in clinical practice also needs to be tested.”

MADRID – The Janus kinase inhibitor tofacitinib had a safety profile mostly similar to that of biologic drugs in a review of more than 8,600 U.S. rheumatoid arthritis patients enrolled in a national registry during 2012-2017, the first 5 years when tofacitinib was on the U.S. market.

Mitchel L. Zoler/MDedge News

The “reassuring” safety performance of tofacitinib (Xeljanz) compared with biologic agents used to treat rheumatoid arthritis (RA) in these registry data notably showed a similar rate of venous thromboembolism (VTE) with tofacitinib treatment compared with biologic drugs, Joel M. Kremer, MD, reported at the European Congress of Rheumatology. It is an important finding because of recent concerns raised about VTE incidence among patients taking tofacitinib or another Janus kinase (JAK) inhibitor, he noted. The registry analysis Dr. Kremer presented showed that patients treated with tofacitinib had slightly more than double the rate of herpes zoster, compared with patients on biologic agents, a finding consistent with prior reports that tofacitinib treatment linked with an almost threefold increased rate of herpes zoster when compared with placebo-treated patients in a series of clinical trials (Arthritis Rheumatol. 2014 Oct;66[10]:2675-84). None of the herpes zoster activations identified in the registry patients on tofacitinib were rated as “serious,” noted Dr. Kremer , professor of medicine at Albany (N.Y.) Medical College.

The analysis he presented used data collected in the Corrona Rheumatoid Arthritis registry during November 2012, the month when tofacitinib received U.S. marketing approval, through December 2017. Data came from RA patients in the registry who began treatment during November 2012–June 2017 with either tofacitinib (1,544 patients) or a biologic agent (7,083 patients). The safety assessment focused on four outcomes: the combined rate of major adverse cardiovascular events (including MI, strokes, and fatal events); the incidence of serious infection; the incidence of any herpes zoster regardless of severity; and VTE. These outcomes were numerous enough to allow for propensity-score matching of patients from the tofacitinib and biologic subgroups to adjust for baseline differences between patients in these two categories, but as of the end of 2017, the cumulative number of VTEs was not high enough to allow for propensity-score adjustment, Dr. Kremer said, so instead he reported the unadjusted numbers. Further data collection should allow an adjusted analysis of VTE within another couple of years, he added. The currently available VTE data were “underpowered” for more rigorous statistical analysis, Dr. Kremer said.

After adjustment, the patients treated with tofacitinib had a 42% lower rate of major cardiovascular events, compared with patients who received a biologic drug, but the difference was not statistically significant, and the two subgroups had virtually identical rates of all serious infections. The incidence of herpes zoster was 2.26-fold more frequent among tofacitinib-treated patients than among those on other biologic agents, a statistically significant difference. The unadjusted VTE analysis showed a rate of 0.19/100 patient-years with tofacitinib treatment, and 0.33/100 patient-years with other biological agents, a difference that was not statistically significant, Dr. Kremer reported. Comparison of the rates of pulmonary embolism and deep vein thrombosis were each not statistically different between the two treatment subgroups.


Concern about possibly increased rates of VTE with the use of tofacitinib or other JAK inhibitors arose recently primarily because of two reports. In February 2019, the Food and Drug Administration released a safety announcement that data from an ongoing, postmarketing study of tofacitinib showed an elevated rate of RA patients with pulmonary embolism when they received an off-label, 10-mg twice-daily dosage of the drug, twice the labeled maximum dosage for this population. (The labeling for tofacitinib allows for a maximum dosage of 10 mg twice daily for patients treated for ulcerative colitis.) In addition, a recent report on another JAK inhibitor approved for U.S. marketing for RA treatment, baricitinib (Olumiant), documented a possible excess of VTE events among patients treated with this drug, compared with those who received placebo (Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40841).

Regarding the now well-described excess of herpes zoster with tofacitinib treatment, Dr. Kremer said that perhaps the best way to address this in a patient who seems to be at risk is to prophylactically vaccinate the patient with the recombinant, adjuvanted zoster vaccine (Shingrix). However, this means withdrawing disease-modifying treatment from the RA patient for 3 weeks at the time of each of two vaccinations, with the possibility of flare induced by the adjuvant, he explained in an interview. The risks and benefits of this approach have not been investigated, he noted, and the Corrona data he studied came almost entirely from the period before Shingrix came onto the U.S. market following its approval in late 2017.

Dr. Kremer has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib. He has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Regeneron/Sanofi, and has received research funding from AbbVie, Eli Lilly, Genentech, and Novartis. One of the coauthors on the report is a Pfizer employee.

mzoler@mdedge.com

SOURCE: Kremer JM et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):82-3; Abstract OP0028. doi: 10.1136/annrheumdis-2019-eular.621.

MADRID – The Janus kinase inhibitor tofacitinib had a safety profile mostly similar to that of biologic drugs in a review of more than 8,600 U.S. rheumatoid arthritis patients enrolled in a national registry during 2012-2017, the first 5 years when tofacitinib was on the U.S. market.

Mitchel L. Zoler/MDedge News

The “reassuring” safety performance of tofacitinib (Xeljanz) compared with biologic agents used to treat rheumatoid arthritis (RA) in these registry data notably showed a similar rate of venous thromboembolism (VTE) with tofacitinib treatment compared with biologic drugs, Joel M. Kremer, MD, reported at the European Congress of Rheumatology. It is an important finding because of recent concerns raised about VTE incidence among patients taking tofacitinib or another Janus kinase (JAK) inhibitor, he noted. The registry analysis Dr. Kremer presented showed that patients treated with tofacitinib had slightly more than double the rate of herpes zoster, compared with patients on biologic agents, a finding consistent with prior reports that tofacitinib treatment linked with an almost threefold increased rate of herpes zoster when compared with placebo-treated patients in a series of clinical trials (Arthritis Rheumatol. 2014 Oct;66[10]:2675-84). None of the herpes zoster activations identified in the registry patients on tofacitinib were rated as “serious,” noted Dr. Kremer , professor of medicine at Albany (N.Y.) Medical College.

The analysis he presented used data collected in the Corrona Rheumatoid Arthritis registry during November 2012, the month when tofacitinib received U.S. marketing approval, through December 2017. Data came from RA patients in the registry who began treatment during November 2012–June 2017 with either tofacitinib (1,544 patients) or a biologic agent (7,083 patients). The safety assessment focused on four outcomes: the combined rate of major adverse cardiovascular events (including MI, strokes, and fatal events); the incidence of serious infection; the incidence of any herpes zoster regardless of severity; and VTE. These outcomes were numerous enough to allow for propensity-score matching of patients from the tofacitinib and biologic subgroups to adjust for baseline differences between patients in these two categories, but as of the end of 2017, the cumulative number of VTEs was not high enough to allow for propensity-score adjustment, Dr. Kremer said, so instead he reported the unadjusted numbers. Further data collection should allow an adjusted analysis of VTE within another couple of years, he added. The currently available VTE data were “underpowered” for more rigorous statistical analysis, Dr. Kremer said.

After adjustment, the patients treated with tofacitinib had a 42% lower rate of major cardiovascular events, compared with patients who received a biologic drug, but the difference was not statistically significant, and the two subgroups had virtually identical rates of all serious infections. The incidence of herpes zoster was 2.26-fold more frequent among tofacitinib-treated patients than among those on other biologic agents, a statistically significant difference. The unadjusted VTE analysis showed a rate of 0.19/100 patient-years with tofacitinib treatment, and 0.33/100 patient-years with other biological agents, a difference that was not statistically significant, Dr. Kremer reported. Comparison of the rates of pulmonary embolism and deep vein thrombosis were each not statistically different between the two treatment subgroups.


Concern about possibly increased rates of VTE with the use of tofacitinib or other JAK inhibitors arose recently primarily because of two reports. In February 2019, the Food and Drug Administration released a safety announcement that data from an ongoing, postmarketing study of tofacitinib showed an elevated rate of RA patients with pulmonary embolism when they received an off-label, 10-mg twice-daily dosage of the drug, twice the labeled maximum dosage for this population. (The labeling for tofacitinib allows for a maximum dosage of 10 mg twice daily for patients treated for ulcerative colitis.) In addition, a recent report on another JAK inhibitor approved for U.S. marketing for RA treatment, baricitinib (Olumiant), documented a possible excess of VTE events among patients treated with this drug, compared with those who received placebo (Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40841).

Regarding the now well-described excess of herpes zoster with tofacitinib treatment, Dr. Kremer said that perhaps the best way to address this in a patient who seems to be at risk is to prophylactically vaccinate the patient with the recombinant, adjuvanted zoster vaccine (Shingrix). However, this means withdrawing disease-modifying treatment from the RA patient for 3 weeks at the time of each of two vaccinations, with the possibility of flare induced by the adjuvant, he explained in an interview. The risks and benefits of this approach have not been investigated, he noted, and the Corrona data he studied came almost entirely from the period before Shingrix came onto the U.S. market following its approval in late 2017.

Dr. Kremer has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib. He has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Regeneron/Sanofi, and has received research funding from AbbVie, Eli Lilly, Genentech, and Novartis. One of the coauthors on the report is a Pfizer employee.

mzoler@mdedge.com

SOURCE: Kremer JM et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):82-3; Abstract OP0028. doi: 10.1136/annrheumdis-2019-eular.621.

MADRID – The Janus kinase inhibitor tofacitinib had a safety profile mostly similar to that of biologic drugs in a review of more than 8,600 U.S. rheumatoid arthritis patients enrolled in a national registry during 2012-2017, the first 5 years when tofacitinib was on the U.S. market.

Mitchel L. Zoler/MDedge News

The “reassuring” safety performance of tofacitinib (Xeljanz) compared with biologic agents used to treat rheumatoid arthritis (RA) in these registry data notably showed a similar rate of venous thromboembolism (VTE) with tofacitinib treatment compared with biologic drugs, Joel M. Kremer, MD, reported at the European Congress of Rheumatology. It is an important finding because of recent concerns raised about VTE incidence among patients taking tofacitinib or another Janus kinase (JAK) inhibitor, he noted. The registry analysis Dr. Kremer presented showed that patients treated with tofacitinib had slightly more than double the rate of herpes zoster, compared with patients on biologic agents, a finding consistent with prior reports that tofacitinib treatment linked with an almost threefold increased rate of herpes zoster when compared with placebo-treated patients in a series of clinical trials (Arthritis Rheumatol. 2014 Oct;66[10]:2675-84). None of the herpes zoster activations identified in the registry patients on tofacitinib were rated as “serious,” noted Dr. Kremer , professor of medicine at Albany (N.Y.) Medical College.

The analysis he presented used data collected in the Corrona Rheumatoid Arthritis registry during November 2012, the month when tofacitinib received U.S. marketing approval, through December 2017. Data came from RA patients in the registry who began treatment during November 2012–June 2017 with either tofacitinib (1,544 patients) or a biologic agent (7,083 patients). The safety assessment focused on four outcomes: the combined rate of major adverse cardiovascular events (including MI, strokes, and fatal events); the incidence of serious infection; the incidence of any herpes zoster regardless of severity; and VTE. These outcomes were numerous enough to allow for propensity-score matching of patients from the tofacitinib and biologic subgroups to adjust for baseline differences between patients in these two categories, but as of the end of 2017, the cumulative number of VTEs was not high enough to allow for propensity-score adjustment, Dr. Kremer said, so instead he reported the unadjusted numbers. Further data collection should allow an adjusted analysis of VTE within another couple of years, he added. The currently available VTE data were “underpowered” for more rigorous statistical analysis, Dr. Kremer said.

After adjustment, the patients treated with tofacitinib had a 42% lower rate of major cardiovascular events, compared with patients who received a biologic drug, but the difference was not statistically significant, and the two subgroups had virtually identical rates of all serious infections. The incidence of herpes zoster was 2.26-fold more frequent among tofacitinib-treated patients than among those on other biologic agents, a statistically significant difference. The unadjusted VTE analysis showed a rate of 0.19/100 patient-years with tofacitinib treatment, and 0.33/100 patient-years with other biological agents, a difference that was not statistically significant, Dr. Kremer reported. Comparison of the rates of pulmonary embolism and deep vein thrombosis were each not statistically different between the two treatment subgroups.


Concern about possibly increased rates of VTE with the use of tofacitinib or other JAK inhibitors arose recently primarily because of two reports. In February 2019, the Food and Drug Administration released a safety announcement that data from an ongoing, postmarketing study of tofacitinib showed an elevated rate of RA patients with pulmonary embolism when they received an off-label, 10-mg twice-daily dosage of the drug, twice the labeled maximum dosage for this population. (The labeling for tofacitinib allows for a maximum dosage of 10 mg twice daily for patients treated for ulcerative colitis.) In addition, a recent report on another JAK inhibitor approved for U.S. marketing for RA treatment, baricitinib (Olumiant), documented a possible excess of VTE events among patients treated with this drug, compared with those who received placebo (Arthritis Rheumatol. 2019 Jan 21. doi: 10.1002/art.40841).

Regarding the now well-described excess of herpes zoster with tofacitinib treatment, Dr. Kremer said that perhaps the best way to address this in a patient who seems to be at risk is to prophylactically vaccinate the patient with the recombinant, adjuvanted zoster vaccine (Shingrix). However, this means withdrawing disease-modifying treatment from the RA patient for 3 weeks at the time of each of two vaccinations, with the possibility of flare induced by the adjuvant, he explained in an interview. The risks and benefits of this approach have not been investigated, he noted, and the Corrona data he studied came almost entirely from the period before Shingrix came onto the U.S. market following its approval in late 2017.

Dr. Kremer has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib. He has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Regeneron/Sanofi, and has received research funding from AbbVie, Eli Lilly, Genentech, and Novartis. One of the coauthors on the report is a Pfizer employee.

mzoler@mdedge.com

SOURCE: Kremer JM et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):82-3; Abstract OP0028. doi: 10.1136/annrheumdis-2019-eular.621.