Rheumatology

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

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“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.

[email protected]

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.

[email protected]

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.

[email protected]

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

About a quarter of all patients with ankylosing spondylitis, and more than half of those patients who were on Medicaid, received at least a 90-day supply of opioids in a year, based on an analysis of U.S. commercial claims data.

sdominick/iStock/Getty Images

The findings were noted in 2012-2017 data from a cohort of 11,945 patients in the Truven Health MarketScan Research database. Of those patients given the International Classification of Diseases (ICD) code 720.0, which is specific for ankylosing spondylitis, 23.5% of patients chronically used opioids. In the broader 720.x commercial claims cohort of 79,190 patients, the proportion who chronically used opioids was 27.3%.

More than 60% of the patients who chronically used opioids had a cumulative drug supply of 270 days or more.

“Patients with ankylosing spondylitis receive opioids with disturbing frequency,” said study author Victor S. Sloan, MD, and research colleagues in the June issue of the Journal of Rheumatology. Ankylosing spondylitis treatment guidelines “specify use of an NSAID as initial pharmacotherapy, with anti-TNF [tumor necrosis factor] therapy in cases of NSAID inefficacy or intolerance. However, for many patients, prescription opioids – while not addressing the underlying inflammation – may offer an inexpensive and rapid means of achieving symptomatic relief.”

Patients who chronically used opioids were more likely to have depression (25.4% vs. 12.5%) and anxiety (20.9% vs. 11.7%) during the baseline period of the study. Patients with chronic opioid use also were more likely to receive muscle relaxants (54.4% vs. 20.2%) and oral corticosteroids (18.4% vs. 9.6%), compared with patients without chronic opioid use, reported Dr. Sloan, vice president and immunology development strategy lead for UCB Pharma and of the Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J., and colleagues.

Claims for anti-TNF therapies, disease-modifying antirheumatic drugs (DMARDs), and NSAIDs were similar for patients with and without chronic opioid use.

The patients in the study had claims with the specified diagnosis codes during Jan. 1, 2013–March 31, 2016 and were enrolled in medical and pharmacy benefits for 12 months before and after the first qualifying ICD code. The study excluded patients with a history of cancer other than nonmelanoma skin cancer. Opioid claims within 7 days of a hospitalization or 2 days of an emergency department or urgent care visit were not included.

The investigators assessed patients’ demographics, clinical characteristics, comorbidities, and prior treatments during a 12-month baseline period prior to the index date. They examined opioid use and exposure to other treatments during a 12-month follow-up period after the index date. They defined chronic opioid use as at least 90 cumulative days of opioid use based on the supply value on opioid pharmacy claims. They summed the days’ supply for all opioid claims during the follow-up period.

Chronic use of opioids was most pronounced in the 917 patients with Medicaid claims with 720.0 diagnosis codes; 57.1% chronically used opioids during follow-up. Among 14,041 patients with Medicaid claims with 720.x codes, 76.7% chronically used opioids.

The data suggest that some patients may receive opioids before they receive recommended therapies. “If this is the case, there may be an opportunity to prevent chronic opioid use by intervening with recommended therapies earlier in the patient’s treatment course,” the authors wrote.

Dr. Sloan and colleagues noted that they had limited information about the timing of opioid use relative to ankylosing spondylitis diagnosis, opioid potency and dose, and the indication for which opioids were prescribed.

UCB Pharma funded the study. The authors are employees of UCB Pharma.

[email protected]

SOURCE: Sloan VS et al. J Rheumatol. 2019 Jan 15. doi: 10.3899/jrheum.180972.

About a quarter of all patients with ankylosing spondylitis, and more than half of those patients who were on Medicaid, received at least a 90-day supply of opioids in a year, based on an analysis of U.S. commercial claims data.

sdominick/iStock/Getty Images

The findings were noted in 2012-2017 data from a cohort of 11,945 patients in the Truven Health MarketScan Research database. Of those patients given the International Classification of Diseases (ICD) code 720.0, which is specific for ankylosing spondylitis, 23.5% of patients chronically used opioids. In the broader 720.x commercial claims cohort of 79,190 patients, the proportion who chronically used opioids was 27.3%.

More than 60% of the patients who chronically used opioids had a cumulative drug supply of 270 days or more.

“Patients with ankylosing spondylitis receive opioids with disturbing frequency,” said study author Victor S. Sloan, MD, and research colleagues in the June issue of the Journal of Rheumatology. Ankylosing spondylitis treatment guidelines “specify use of an NSAID as initial pharmacotherapy, with anti-TNF [tumor necrosis factor] therapy in cases of NSAID inefficacy or intolerance. However, for many patients, prescription opioids – while not addressing the underlying inflammation – may offer an inexpensive and rapid means of achieving symptomatic relief.”

Patients who chronically used opioids were more likely to have depression (25.4% vs. 12.5%) and anxiety (20.9% vs. 11.7%) during the baseline period of the study. Patients with chronic opioid use also were more likely to receive muscle relaxants (54.4% vs. 20.2%) and oral corticosteroids (18.4% vs. 9.6%), compared with patients without chronic opioid use, reported Dr. Sloan, vice president and immunology development strategy lead for UCB Pharma and of the Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J., and colleagues.

Claims for anti-TNF therapies, disease-modifying antirheumatic drugs (DMARDs), and NSAIDs were similar for patients with and without chronic opioid use.

The patients in the study had claims with the specified diagnosis codes during Jan. 1, 2013–March 31, 2016 and were enrolled in medical and pharmacy benefits for 12 months before and after the first qualifying ICD code. The study excluded patients with a history of cancer other than nonmelanoma skin cancer. Opioid claims within 7 days of a hospitalization or 2 days of an emergency department or urgent care visit were not included.

The investigators assessed patients’ demographics, clinical characteristics, comorbidities, and prior treatments during a 12-month baseline period prior to the index date. They examined opioid use and exposure to other treatments during a 12-month follow-up period after the index date. They defined chronic opioid use as at least 90 cumulative days of opioid use based on the supply value on opioid pharmacy claims. They summed the days’ supply for all opioid claims during the follow-up period.

Chronic use of opioids was most pronounced in the 917 patients with Medicaid claims with 720.0 diagnosis codes; 57.1% chronically used opioids during follow-up. Among 14,041 patients with Medicaid claims with 720.x codes, 76.7% chronically used opioids.

The data suggest that some patients may receive opioids before they receive recommended therapies. “If this is the case, there may be an opportunity to prevent chronic opioid use by intervening with recommended therapies earlier in the patient’s treatment course,” the authors wrote.

Dr. Sloan and colleagues noted that they had limited information about the timing of opioid use relative to ankylosing spondylitis diagnosis, opioid potency and dose, and the indication for which opioids were prescribed.

UCB Pharma funded the study. The authors are employees of UCB Pharma.

[email protected]

SOURCE: Sloan VS et al. J Rheumatol. 2019 Jan 15. doi: 10.3899/jrheum.180972.

About a quarter of all patients with ankylosing spondylitis, and more than half of those patients who were on Medicaid, received at least a 90-day supply of opioids in a year, based on an analysis of U.S. commercial claims data.

sdominick/iStock/Getty Images

The findings were noted in 2012-2017 data from a cohort of 11,945 patients in the Truven Health MarketScan Research database. Of those patients given the International Classification of Diseases (ICD) code 720.0, which is specific for ankylosing spondylitis, 23.5% of patients chronically used opioids. In the broader 720.x commercial claims cohort of 79,190 patients, the proportion who chronically used opioids was 27.3%.

More than 60% of the patients who chronically used opioids had a cumulative drug supply of 270 days or more.

“Patients with ankylosing spondylitis receive opioids with disturbing frequency,” said study author Victor S. Sloan, MD, and research colleagues in the June issue of the Journal of Rheumatology. Ankylosing spondylitis treatment guidelines “specify use of an NSAID as initial pharmacotherapy, with anti-TNF [tumor necrosis factor] therapy in cases of NSAID inefficacy or intolerance. However, for many patients, prescription opioids – while not addressing the underlying inflammation – may offer an inexpensive and rapid means of achieving symptomatic relief.”

Patients who chronically used opioids were more likely to have depression (25.4% vs. 12.5%) and anxiety (20.9% vs. 11.7%) during the baseline period of the study. Patients with chronic opioid use also were more likely to receive muscle relaxants (54.4% vs. 20.2%) and oral corticosteroids (18.4% vs. 9.6%), compared with patients without chronic opioid use, reported Dr. Sloan, vice president and immunology development strategy lead for UCB Pharma and of the Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J., and colleagues.

Claims for anti-TNF therapies, disease-modifying antirheumatic drugs (DMARDs), and NSAIDs were similar for patients with and without chronic opioid use.

The patients in the study had claims with the specified diagnosis codes during Jan. 1, 2013–March 31, 2016 and were enrolled in medical and pharmacy benefits for 12 months before and after the first qualifying ICD code. The study excluded patients with a history of cancer other than nonmelanoma skin cancer. Opioid claims within 7 days of a hospitalization or 2 days of an emergency department or urgent care visit were not included.

The investigators assessed patients’ demographics, clinical characteristics, comorbidities, and prior treatments during a 12-month baseline period prior to the index date. They examined opioid use and exposure to other treatments during a 12-month follow-up period after the index date. They defined chronic opioid use as at least 90 cumulative days of opioid use based on the supply value on opioid pharmacy claims. They summed the days’ supply for all opioid claims during the follow-up period.

Chronic use of opioids was most pronounced in the 917 patients with Medicaid claims with 720.0 diagnosis codes; 57.1% chronically used opioids during follow-up. Among 14,041 patients with Medicaid claims with 720.x codes, 76.7% chronically used opioids.

The data suggest that some patients may receive opioids before they receive recommended therapies. “If this is the case, there may be an opportunity to prevent chronic opioid use by intervening with recommended therapies earlier in the patient’s treatment course,” the authors wrote.

Dr. Sloan and colleagues noted that they had limited information about the timing of opioid use relative to ankylosing spondylitis diagnosis, opioid potency and dose, and the indication for which opioids were prescribed.

UCB Pharma funded the study. The authors are employees of UCB Pharma.

[email protected]

SOURCE: Sloan VS et al. J Rheumatol. 2019 Jan 15. doi: 10.3899/jrheum.180972.

The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.

“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.

The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.

Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.

An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).

A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).

The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.

“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.

Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).

Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.

“This favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic] DMARDs,” the authors wrote.

The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.

SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2

The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.

“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.

The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.

Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.

An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).

A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).

The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.

“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.

Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).

Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.

“This favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic] DMARDs,” the authors wrote.

The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.

SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2

The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.

“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.

The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.

Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.

An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).

A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).

The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.

“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.

Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).

Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.

“This favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic] DMARDs,” the authors wrote.

The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.

SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2

Monitoring immunoglobulin (Ig) levels at baseline and before each cycle of rituximab could reduce the risk of serious infection events (SIEs) in patients needing repeated treatment, according to research published in Arthritis & Rheumatology.

In a large, single-center, longitudinal study conducted at a tertiary referral center, having low IgG (less than 6 g/L) in particular was associated with a higher rate of SIEs, compared with having normal IgG levels (6-16 g/L). Considering 103 of 700 patients who had low levels of IgG before starting treatment with rituximab for various rheumatic and musculoskeletal diseases (RMDs), there were 16.4 SIEs per 100 patient-years. In those who developed low IgG during subsequent cycles of rituximab therapy, the SIE rate was even higher, at 21.3 per 100 patient-years. By comparison, the SIE rate for those with normal IgG levels was 9.7 per 100 patient-years.

“We really have to monitor immunoglobulins at baseline and also before we re-treat the patients, because higher IgG level is protective of serious infections,” study first author Md Yuzaiful Md Yusof, MBChB, PhD, said in an interview.

Low IgG has been linked to a higher risk of SIEs in the first 12 months of rituximab therapy but, until now, there have been limited data on infection predictors during repeated cycles of treatment. While IgG is a consistent marker of SIEs associated with repeated rituximab treatment, IgM and IgA should also be monitored to give a full picture of any hyperglobulinemia that may be present.

“There is no formal guidance on how to safely monitor patients on rituximab,” observed Dr. Md Yusof, who will present these data at the 2019 European Congress of Rheumatology in Madrid. The study’s findings could help to change that, however, as they offer a practical way to help predict and thus prevent SIEs. The study’s findings not only validate previous work, he noted, but also add new insights into why some patients treated with repeat rituximab cycles but not others may experience a higher rate of such infections.

Altogether, the investigators examined data on 700 patients with RMDs treated with rituximab who were consecutively seen during 2012-2017 at Dr. Md Yusof’s institution – the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, which is part of the University of Leeds. Their immunoglobulin levels had been measured before starting rituximab therapy and every 4-6 months after each cycle of rituximab treatment.

Patients with any RMD being treated with at least one cycle of rituximab were eligible for inclusion in the retrospective study, with the majority (72%) taking it for rheumatoid arthritis and some for systemic lupus erythematosus (13%) or antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (7%).

One of the main aims of the study was to look for predictors of SIEs during the first 12 months and during repeated cycles of rituximab. Dr. Md Yusof and his associates also looked at how secondary hypogammaglobulinemia might affect SIE rates and the humoral response to vaccination challenge and its persistence following treatment discontinuation. Their ultimate aim was to see if these findings could then be used to develop a treatment algorithm for rituximab administration in RMDs.

Over a follow-up period encompassing 2,880 patient-years of treatment, 281 SIEs were recorded in 176 patients, giving a rate of 9.8 infections per 100 patient-years. Most (61%) of these were due to lower respiratory tract infections.

The proportion of patients experiencing their first SIE increased with time: 16% within 6 weeks of starting rituximab therapy, 35% at 12 weeks, 72% at 26 weeks, 83% at 38 weeks, and 100% by 1 year of repeated treatment.

Multivariable analysis showed that the presence of several comorbidities at baseline – notably chronic obstructive pulmonary disease, diabetes, heart failure, and prior cancer – raised the risk for SIEs with repeated rituximab therapy. The biggest factor, however, was a history of SIEs – with a sixfold increased risk of further serious infection.

Higher corticosteroid dose and factors specific to rituximab – low IgG, neutropenia, high IgM, and a longer time to retreatment – were also predictive of SIEs.

“Low IgG also results in poor humoral response to vaccination,” Dr. Md Yusof said, noting that the IgG level remains below the lower limit of normal for several years after rituximab is discontinued in most patients.

In the study, 5 of 8 (64%) patients had impaired humoral response to pneumococcal and haemophilus following vaccination challenge and 4 of 11 patients had IgG normalized after switching to another biologic disease-modifying antirheumatic drug (bDMARD).

Cyclophosphamide is commonly used as a first-line agent to induce remission in patients with severe and refractory systemic lupus erythematosus and ANCA-associated vasculitis, with patients switched to rituximab at relapse. The effect of this prior treatment was examined in 20 patients in the study, with a marked decline in almost all immunoglobulin classes seen up to 18 months. Prior treatment with immunosuppressants such as intravenous cyclophosphamide could be behind progressive reductions in Ig levels seen with repeated rituximab treatment rather than entirely because of rituximab, Dr. Md Yusof said.

Dr. Md Yusof, who is a National Institute for Health Research (NIHR) Academic Clinical Lecturer at the University of Leeds, said the value of the study, compared with others, is that hospital data for all patients treated with rituximab with at least 3 months follow-up were included, making it an almost complete data set.

“By carefully reviewing records of every patient to capture all infection episodes in the largest single-center cohort study to date, our findings provide insights on predictors of SIEs as well as a foundation for safety monitoring of rituximab,” he and his coauthors wrote.

They acknowledge reporting a higher rate of SIEs than seen in registry and clinical studies with rituximab, which may reflect a “channeling bias” as the patients comprised those with multiple comorbidities including those that represent a relative contraindication for bDMARD use. That said, the findings clearly show that Ig levels should be monitored before and after each rituximab cycle, especially in those with comorbid diseases and those with low IgG levels to start with.

They conclude that an “individualized benefit-risk assessment” is needed to determine whether rituximab should be repeated in those with low IgG as this is a “consistent predictor” of SIE and may “increase infection profiles when [rituximab] is switched to different bDMARDs.”

The research was supported by Octapharma, the National Institute for Health Research (NIHR), and NIHR Leeds Biomedical Research Centre based at Leeds Teaching Hospitals NHS Trust in England. Dr. Md Yusof had no conflicts of interest. Several coauthors disclosed financial ties to multiple pharmaceutical companies, including Roche.

SOURCE: Md Yusof MY et al. Arthritis Rheumatol. 2019 May 27. doi: 10.1002/art.40937.

Monitoring immunoglobulin (Ig) levels at baseline and before each cycle of rituximab could reduce the risk of serious infection events (SIEs) in patients needing repeated treatment, according to research published in Arthritis & Rheumatology.

In a large, single-center, longitudinal study conducted at a tertiary referral center, having low IgG (less than 6 g/L) in particular was associated with a higher rate of SIEs, compared with having normal IgG levels (6-16 g/L). Considering 103 of 700 patients who had low levels of IgG before starting treatment with rituximab for various rheumatic and musculoskeletal diseases (RMDs), there were 16.4 SIEs per 100 patient-years. In those who developed low IgG during subsequent cycles of rituximab therapy, the SIE rate was even higher, at 21.3 per 100 patient-years. By comparison, the SIE rate for those with normal IgG levels was 9.7 per 100 patient-years.

“We really have to monitor immunoglobulins at baseline and also before we re-treat the patients, because higher IgG level is protective of serious infections,” study first author Md Yuzaiful Md Yusof, MBChB, PhD, said in an interview.

Low IgG has been linked to a higher risk of SIEs in the first 12 months of rituximab therapy but, until now, there have been limited data on infection predictors during repeated cycles of treatment. While IgG is a consistent marker of SIEs associated with repeated rituximab treatment, IgM and IgA should also be monitored to give a full picture of any hyperglobulinemia that may be present.

“There is no formal guidance on how to safely monitor patients on rituximab,” observed Dr. Md Yusof, who will present these data at the 2019 European Congress of Rheumatology in Madrid. The study’s findings could help to change that, however, as they offer a practical way to help predict and thus prevent SIEs. The study’s findings not only validate previous work, he noted, but also add new insights into why some patients treated with repeat rituximab cycles but not others may experience a higher rate of such infections.

Altogether, the investigators examined data on 700 patients with RMDs treated with rituximab who were consecutively seen during 2012-2017 at Dr. Md Yusof’s institution – the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, which is part of the University of Leeds. Their immunoglobulin levels had been measured before starting rituximab therapy and every 4-6 months after each cycle of rituximab treatment.

Patients with any RMD being treated with at least one cycle of rituximab were eligible for inclusion in the retrospective study, with the majority (72%) taking it for rheumatoid arthritis and some for systemic lupus erythematosus (13%) or antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (7%).

One of the main aims of the study was to look for predictors of SIEs during the first 12 months and during repeated cycles of rituximab. Dr. Md Yusof and his associates also looked at how secondary hypogammaglobulinemia might affect SIE rates and the humoral response to vaccination challenge and its persistence following treatment discontinuation. Their ultimate aim was to see if these findings could then be used to develop a treatment algorithm for rituximab administration in RMDs.

Over a follow-up period encompassing 2,880 patient-years of treatment, 281 SIEs were recorded in 176 patients, giving a rate of 9.8 infections per 100 patient-years. Most (61%) of these were due to lower respiratory tract infections.

The proportion of patients experiencing their first SIE increased with time: 16% within 6 weeks of starting rituximab therapy, 35% at 12 weeks, 72% at 26 weeks, 83% at 38 weeks, and 100% by 1 year of repeated treatment.

Multivariable analysis showed that the presence of several comorbidities at baseline – notably chronic obstructive pulmonary disease, diabetes, heart failure, and prior cancer – raised the risk for SIEs with repeated rituximab therapy. The biggest factor, however, was a history of SIEs – with a sixfold increased risk of further serious infection.

Higher corticosteroid dose and factors specific to rituximab – low IgG, neutropenia, high IgM, and a longer time to retreatment – were also predictive of SIEs.

“Low IgG also results in poor humoral response to vaccination,” Dr. Md Yusof said, noting that the IgG level remains below the lower limit of normal for several years after rituximab is discontinued in most patients.

In the study, 5 of 8 (64%) patients had impaired humoral response to pneumococcal and haemophilus following vaccination challenge and 4 of 11 patients had IgG normalized after switching to another biologic disease-modifying antirheumatic drug (bDMARD).

Cyclophosphamide is commonly used as a first-line agent to induce remission in patients with severe and refractory systemic lupus erythematosus and ANCA-associated vasculitis, with patients switched to rituximab at relapse. The effect of this prior treatment was examined in 20 patients in the study, with a marked decline in almost all immunoglobulin classes seen up to 18 months. Prior treatment with immunosuppressants such as intravenous cyclophosphamide could be behind progressive reductions in Ig levels seen with repeated rituximab treatment rather than entirely because of rituximab, Dr. Md Yusof said.

Dr. Md Yusof, who is a National Institute for Health Research (NIHR) Academic Clinical Lecturer at the University of Leeds, said the value of the study, compared with others, is that hospital data for all patients treated with rituximab with at least 3 months follow-up were included, making it an almost complete data set.

“By carefully reviewing records of every patient to capture all infection episodes in the largest single-center cohort study to date, our findings provide insights on predictors of SIEs as well as a foundation for safety monitoring of rituximab,” he and his coauthors wrote.

They acknowledge reporting a higher rate of SIEs than seen in registry and clinical studies with rituximab, which may reflect a “channeling bias” as the patients comprised those with multiple comorbidities including those that represent a relative contraindication for bDMARD use. That said, the findings clearly show that Ig levels should be monitored before and after each rituximab cycle, especially in those with comorbid diseases and those with low IgG levels to start with.

They conclude that an “individualized benefit-risk assessment” is needed to determine whether rituximab should be repeated in those with low IgG as this is a “consistent predictor” of SIE and may “increase infection profiles when [rituximab] is switched to different bDMARDs.”

The research was supported by Octapharma, the National Institute for Health Research (NIHR), and NIHR Leeds Biomedical Research Centre based at Leeds Teaching Hospitals NHS Trust in England. Dr. Md Yusof had no conflicts of interest. Several coauthors disclosed financial ties to multiple pharmaceutical companies, including Roche.

SOURCE: Md Yusof MY et al. Arthritis Rheumatol. 2019 May 27. doi: 10.1002/art.40937.

Monitoring immunoglobulin (Ig) levels at baseline and before each cycle of rituximab could reduce the risk of serious infection events (SIEs) in patients needing repeated treatment, according to research published in Arthritis & Rheumatology.

In a large, single-center, longitudinal study conducted at a tertiary referral center, having low IgG (less than 6 g/L) in particular was associated with a higher rate of SIEs, compared with having normal IgG levels (6-16 g/L). Considering 103 of 700 patients who had low levels of IgG before starting treatment with rituximab for various rheumatic and musculoskeletal diseases (RMDs), there were 16.4 SIEs per 100 patient-years. In those who developed low IgG during subsequent cycles of rituximab therapy, the SIE rate was even higher, at 21.3 per 100 patient-years. By comparison, the SIE rate for those with normal IgG levels was 9.7 per 100 patient-years.

“We really have to monitor immunoglobulins at baseline and also before we re-treat the patients, because higher IgG level is protective of serious infections,” study first author Md Yuzaiful Md Yusof, MBChB, PhD, said in an interview.

Low IgG has been linked to a higher risk of SIEs in the first 12 months of rituximab therapy but, until now, there have been limited data on infection predictors during repeated cycles of treatment. While IgG is a consistent marker of SIEs associated with repeated rituximab treatment, IgM and IgA should also be monitored to give a full picture of any hyperglobulinemia that may be present.

“There is no formal guidance on how to safely monitor patients on rituximab,” observed Dr. Md Yusof, who will present these data at the 2019 European Congress of Rheumatology in Madrid. The study’s findings could help to change that, however, as they offer a practical way to help predict and thus prevent SIEs. The study’s findings not only validate previous work, he noted, but also add new insights into why some patients treated with repeat rituximab cycles but not others may experience a higher rate of such infections.

Altogether, the investigators examined data on 700 patients with RMDs treated with rituximab who were consecutively seen during 2012-2017 at Dr. Md Yusof’s institution – the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, which is part of the University of Leeds. Their immunoglobulin levels had been measured before starting rituximab therapy and every 4-6 months after each cycle of rituximab treatment.

Patients with any RMD being treated with at least one cycle of rituximab were eligible for inclusion in the retrospective study, with the majority (72%) taking it for rheumatoid arthritis and some for systemic lupus erythematosus (13%) or antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (7%).

One of the main aims of the study was to look for predictors of SIEs during the first 12 months and during repeated cycles of rituximab. Dr. Md Yusof and his associates also looked at how secondary hypogammaglobulinemia might affect SIE rates and the humoral response to vaccination challenge and its persistence following treatment discontinuation. Their ultimate aim was to see if these findings could then be used to develop a treatment algorithm for rituximab administration in RMDs.

Over a follow-up period encompassing 2,880 patient-years of treatment, 281 SIEs were recorded in 176 patients, giving a rate of 9.8 infections per 100 patient-years. Most (61%) of these were due to lower respiratory tract infections.

The proportion of patients experiencing their first SIE increased with time: 16% within 6 weeks of starting rituximab therapy, 35% at 12 weeks, 72% at 26 weeks, 83% at 38 weeks, and 100% by 1 year of repeated treatment.

Multivariable analysis showed that the presence of several comorbidities at baseline – notably chronic obstructive pulmonary disease, diabetes, heart failure, and prior cancer – raised the risk for SIEs with repeated rituximab therapy. The biggest factor, however, was a history of SIEs – with a sixfold increased risk of further serious infection.

Higher corticosteroid dose and factors specific to rituximab – low IgG, neutropenia, high IgM, and a longer time to retreatment – were also predictive of SIEs.

“Low IgG also results in poor humoral response to vaccination,” Dr. Md Yusof said, noting that the IgG level remains below the lower limit of normal for several years after rituximab is discontinued in most patients.

In the study, 5 of 8 (64%) patients had impaired humoral response to pneumococcal and haemophilus following vaccination challenge and 4 of 11 patients had IgG normalized after switching to another biologic disease-modifying antirheumatic drug (bDMARD).

Cyclophosphamide is commonly used as a first-line agent to induce remission in patients with severe and refractory systemic lupus erythematosus and ANCA-associated vasculitis, with patients switched to rituximab at relapse. The effect of this prior treatment was examined in 20 patients in the study, with a marked decline in almost all immunoglobulin classes seen up to 18 months. Prior treatment with immunosuppressants such as intravenous cyclophosphamide could be behind progressive reductions in Ig levels seen with repeated rituximab treatment rather than entirely because of rituximab, Dr. Md Yusof said.

Dr. Md Yusof, who is a National Institute for Health Research (NIHR) Academic Clinical Lecturer at the University of Leeds, said the value of the study, compared with others, is that hospital data for all patients treated with rituximab with at least 3 months follow-up were included, making it an almost complete data set.

“By carefully reviewing records of every patient to capture all infection episodes in the largest single-center cohort study to date, our findings provide insights on predictors of SIEs as well as a foundation for safety monitoring of rituximab,” he and his coauthors wrote.

They acknowledge reporting a higher rate of SIEs than seen in registry and clinical studies with rituximab, which may reflect a “channeling bias” as the patients comprised those with multiple comorbidities including those that represent a relative contraindication for bDMARD use. That said, the findings clearly show that Ig levels should be monitored before and after each rituximab cycle, especially in those with comorbid diseases and those with low IgG levels to start with.

They conclude that an “individualized benefit-risk assessment” is needed to determine whether rituximab should be repeated in those with low IgG as this is a “consistent predictor” of SIE and may “increase infection profiles when [rituximab] is switched to different bDMARDs.”

The research was supported by Octapharma, the National Institute for Health Research (NIHR), and NIHR Leeds Biomedical Research Centre based at Leeds Teaching Hospitals NHS Trust in England. Dr. Md Yusof had no conflicts of interest. Several coauthors disclosed financial ties to multiple pharmaceutical companies, including Roche.

SOURCE: Md Yusof MY et al. Arthritis Rheumatol. 2019 May 27. doi: 10.1002/art.40937.

TORONTO – A Swedish national primary care–centered self-management program for patients with knee or hip osteoarthritis (OA) resulted in clinically meaningful improvements through 1 year of follow-up in an observational registry study of 47,035 participants, Therese S. Jönsson reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“The BOA [Better management of patients with Osteoarthritis] program is feasible and demonstrates positive results in a large clinical context. Our results indicate that offering this intervention as the first-line treatment for patients with hip and knee osteoarthritis may reduce the burden of disease,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Indeed, the results of the Swedish BOA program for nonsurgical treatment of OA played an influential role in the new draft of OARSI guidelines for management of knee osteoarthritis. The program could serve as a template for implementation of a similar approach in other health care settings. The BOA program has been rolled out to more than 700 Swedish primary care practice sites, according to Ms. Jönsson, a PhD student at Lund (Sweden) University.

The program was created to meet a defined national goal that, as early as possible in the course of the disease, every Swedish patient with knee or hip OA should receive education about their disease and the importance of exercise as a means of improving their quality of life. The impetus for BOA was a widespread concern that, in Sweden and elsewhere, far too many OA patients were being referred for joint surgery without ever having tried the evidence-based core nonsurgical treatments.
 

The BOA intervention

Following patient referral by a primary care physician, the Swedish BOA program starts off with individual assessment and biomechanical testing by a physical therapist. This is followed by two small-group education sessions of about 90 minutes led by a physical therapist or occupational therapist. Session one includes information about the pathology of OA, risk factors, symptoms, and the available treatments. Session two focuses on coping skills, self-management strategies to reduce pain and symptoms, the central role of exercise as a core treatment in OA, and ways to incorporate physical activity into daily living.

Then comes a decision point. Having listened to a motivational message extolling the benefits of exercise as a means of empowering self-management of their chronic disease, participants next have three choices: They can attend supervised group exercise classes twice weekly for 6 weeks to kick-start a more physically active lifestyle, they can start an individually adapted home exercise program, or they can decline exercise.

Giving patients a choice in this matter is a strategy rooted in the psychological concept of motivational stages of change, which recognizes that some patients with a chronic illness whose course is modifiable through lifestyle change are initially in a precontemplation stage of change. And pushing them hard at that point is counterproductive. The home exercise option, which permits patients to take a low-and-slow approach to exercise, is based upon the BOA program developers’ stated philosophy that 5 minutes of exercise daily, performed as part of everyday life, has a bigger impact upon function than does a 30-minute exercise program that’s abandoned after a few weeks. The goal of the BOA program is for patients to eventually build up to at least 150 minutes of moderate-intensity exercise per week.
 

The results

Roughly 15% of patients enrolled in the registry declined the exercise option. Ms. Jönsson’s analysis focused on those who opted to participate in an exercise program, 40% of whom selected the home exercise option. This analysis included 30,682 patients with knee OA and 16,363 with hip OA. They returned to the physical therapist for a face-to-face reassessment after 3 months, and they completed a mailed outcome-oriented questionnaire at 12 months.

The BOA intervention was more effective in reducing pain in the knee OA group than in those with hip OA. A statistically significant reduction in self-assessed pain scores on a 0-10 scale was seen in both the knee and hip OA groups at 3 and 12 months; however, only the knee OA patients achieved a clinically important decrease in pain, defined as at least a 15% drop in pain scores. Their pain scores improved from 5.24 at baseline to 4.07 at 3 months and 4.23 at 12 months. In the hip OA patients, pain scores went from 5.39 at baseline to 4.56 at 3 months and 4.7 at 12 months.

However, at 3 and 12 months, significantly fewer patients in both the hip and knee OA groups reported experiencing pain more than once per week, compared with baseline. They also took fewer pain-killing medications, reported less avoidance behavior involving fear of movement, were less willing to undergo joint surgery, and scored significantly higher on the five-level EQ-5D quality-of-life measure than at baseline. Moreover, fewer patients were on sick leave at the 12-month follow-up than at baseline, an outcome that wasn’t assessed at 3 months.

Adherence to the group exercise classes was “quite low,” according to Ms. Jönsson, and poor adherence was reflected in smaller reductions in pain scores. Only 30% of patients who elected the supervised group exercise option attended 10 of the 12 sessions, she noted.

Ms. Jönsson reported having no financial conflicts regarding her study. The BOA program is funded by the Swedish government.

[email protected]

SOURCE: Jönsson TS et al. Osteoarthritis Cartilage. 2019 Apr;27(suppl 1):S497, Abstract 717.

TORONTO – A Swedish national primary care–centered self-management program for patients with knee or hip osteoarthritis (OA) resulted in clinically meaningful improvements through 1 year of follow-up in an observational registry study of 47,035 participants, Therese S. Jönsson reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“The BOA [Better management of patients with Osteoarthritis] program is feasible and demonstrates positive results in a large clinical context. Our results indicate that offering this intervention as the first-line treatment for patients with hip and knee osteoarthritis may reduce the burden of disease,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Indeed, the results of the Swedish BOA program for nonsurgical treatment of OA played an influential role in the new draft of OARSI guidelines for management of knee osteoarthritis. The program could serve as a template for implementation of a similar approach in other health care settings. The BOA program has been rolled out to more than 700 Swedish primary care practice sites, according to Ms. Jönsson, a PhD student at Lund (Sweden) University.

The program was created to meet a defined national goal that, as early as possible in the course of the disease, every Swedish patient with knee or hip OA should receive education about their disease and the importance of exercise as a means of improving their quality of life. The impetus for BOA was a widespread concern that, in Sweden and elsewhere, far too many OA patients were being referred for joint surgery without ever having tried the evidence-based core nonsurgical treatments.
 

The BOA intervention

Following patient referral by a primary care physician, the Swedish BOA program starts off with individual assessment and biomechanical testing by a physical therapist. This is followed by two small-group education sessions of about 90 minutes led by a physical therapist or occupational therapist. Session one includes information about the pathology of OA, risk factors, symptoms, and the available treatments. Session two focuses on coping skills, self-management strategies to reduce pain and symptoms, the central role of exercise as a core treatment in OA, and ways to incorporate physical activity into daily living.

Then comes a decision point. Having listened to a motivational message extolling the benefits of exercise as a means of empowering self-management of their chronic disease, participants next have three choices: They can attend supervised group exercise classes twice weekly for 6 weeks to kick-start a more physically active lifestyle, they can start an individually adapted home exercise program, or they can decline exercise.

Giving patients a choice in this matter is a strategy rooted in the psychological concept of motivational stages of change, which recognizes that some patients with a chronic illness whose course is modifiable through lifestyle change are initially in a precontemplation stage of change. And pushing them hard at that point is counterproductive. The home exercise option, which permits patients to take a low-and-slow approach to exercise, is based upon the BOA program developers’ stated philosophy that 5 minutes of exercise daily, performed as part of everyday life, has a bigger impact upon function than does a 30-minute exercise program that’s abandoned after a few weeks. The goal of the BOA program is for patients to eventually build up to at least 150 minutes of moderate-intensity exercise per week.
 

The results

Roughly 15% of patients enrolled in the registry declined the exercise option. Ms. Jönsson’s analysis focused on those who opted to participate in an exercise program, 40% of whom selected the home exercise option. This analysis included 30,682 patients with knee OA and 16,363 with hip OA. They returned to the physical therapist for a face-to-face reassessment after 3 months, and they completed a mailed outcome-oriented questionnaire at 12 months.

The BOA intervention was more effective in reducing pain in the knee OA group than in those with hip OA. A statistically significant reduction in self-assessed pain scores on a 0-10 scale was seen in both the knee and hip OA groups at 3 and 12 months; however, only the knee OA patients achieved a clinically important decrease in pain, defined as at least a 15% drop in pain scores. Their pain scores improved from 5.24 at baseline to 4.07 at 3 months and 4.23 at 12 months. In the hip OA patients, pain scores went from 5.39 at baseline to 4.56 at 3 months and 4.7 at 12 months.

However, at 3 and 12 months, significantly fewer patients in both the hip and knee OA groups reported experiencing pain more than once per week, compared with baseline. They also took fewer pain-killing medications, reported less avoidance behavior involving fear of movement, were less willing to undergo joint surgery, and scored significantly higher on the five-level EQ-5D quality-of-life measure than at baseline. Moreover, fewer patients were on sick leave at the 12-month follow-up than at baseline, an outcome that wasn’t assessed at 3 months.

Adherence to the group exercise classes was “quite low,” according to Ms. Jönsson, and poor adherence was reflected in smaller reductions in pain scores. Only 30% of patients who elected the supervised group exercise option attended 10 of the 12 sessions, she noted.

Ms. Jönsson reported having no financial conflicts regarding her study. The BOA program is funded by the Swedish government.

[email protected]

SOURCE: Jönsson TS et al. Osteoarthritis Cartilage. 2019 Apr;27(suppl 1):S497, Abstract 717.

TORONTO – A Swedish national primary care–centered self-management program for patients with knee or hip osteoarthritis (OA) resulted in clinically meaningful improvements through 1 year of follow-up in an observational registry study of 47,035 participants, Therese S. Jönsson reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“The BOA [Better management of patients with Osteoarthritis] program is feasible and demonstrates positive results in a large clinical context. Our results indicate that offering this intervention as the first-line treatment for patients with hip and knee osteoarthritis may reduce the burden of disease,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Indeed, the results of the Swedish BOA program for nonsurgical treatment of OA played an influential role in the new draft of OARSI guidelines for management of knee osteoarthritis. The program could serve as a template for implementation of a similar approach in other health care settings. The BOA program has been rolled out to more than 700 Swedish primary care practice sites, according to Ms. Jönsson, a PhD student at Lund (Sweden) University.

The program was created to meet a defined national goal that, as early as possible in the course of the disease, every Swedish patient with knee or hip OA should receive education about their disease and the importance of exercise as a means of improving their quality of life. The impetus for BOA was a widespread concern that, in Sweden and elsewhere, far too many OA patients were being referred for joint surgery without ever having tried the evidence-based core nonsurgical treatments.
 

The BOA intervention

Following patient referral by a primary care physician, the Swedish BOA program starts off with individual assessment and biomechanical testing by a physical therapist. This is followed by two small-group education sessions of about 90 minutes led by a physical therapist or occupational therapist. Session one includes information about the pathology of OA, risk factors, symptoms, and the available treatments. Session two focuses on coping skills, self-management strategies to reduce pain and symptoms, the central role of exercise as a core treatment in OA, and ways to incorporate physical activity into daily living.

Then comes a decision point. Having listened to a motivational message extolling the benefits of exercise as a means of empowering self-management of their chronic disease, participants next have three choices: They can attend supervised group exercise classes twice weekly for 6 weeks to kick-start a more physically active lifestyle, they can start an individually adapted home exercise program, or they can decline exercise.

Giving patients a choice in this matter is a strategy rooted in the psychological concept of motivational stages of change, which recognizes that some patients with a chronic illness whose course is modifiable through lifestyle change are initially in a precontemplation stage of change. And pushing them hard at that point is counterproductive. The home exercise option, which permits patients to take a low-and-slow approach to exercise, is based upon the BOA program developers’ stated philosophy that 5 minutes of exercise daily, performed as part of everyday life, has a bigger impact upon function than does a 30-minute exercise program that’s abandoned after a few weeks. The goal of the BOA program is for patients to eventually build up to at least 150 minutes of moderate-intensity exercise per week.
 

The results

Roughly 15% of patients enrolled in the registry declined the exercise option. Ms. Jönsson’s analysis focused on those who opted to participate in an exercise program, 40% of whom selected the home exercise option. This analysis included 30,682 patients with knee OA and 16,363 with hip OA. They returned to the physical therapist for a face-to-face reassessment after 3 months, and they completed a mailed outcome-oriented questionnaire at 12 months.

The BOA intervention was more effective in reducing pain in the knee OA group than in those with hip OA. A statistically significant reduction in self-assessed pain scores on a 0-10 scale was seen in both the knee and hip OA groups at 3 and 12 months; however, only the knee OA patients achieved a clinically important decrease in pain, defined as at least a 15% drop in pain scores. Their pain scores improved from 5.24 at baseline to 4.07 at 3 months and 4.23 at 12 months. In the hip OA patients, pain scores went from 5.39 at baseline to 4.56 at 3 months and 4.7 at 12 months.

However, at 3 and 12 months, significantly fewer patients in both the hip and knee OA groups reported experiencing pain more than once per week, compared with baseline. They also took fewer pain-killing medications, reported less avoidance behavior involving fear of movement, were less willing to undergo joint surgery, and scored significantly higher on the five-level EQ-5D quality-of-life measure than at baseline. Moreover, fewer patients were on sick leave at the 12-month follow-up than at baseline, an outcome that wasn’t assessed at 3 months.

Adherence to the group exercise classes was “quite low,” according to Ms. Jönsson, and poor adherence was reflected in smaller reductions in pain scores. Only 30% of patients who elected the supervised group exercise option attended 10 of the 12 sessions, she noted.

Ms. Jönsson reported having no financial conflicts regarding her study. The BOA program is funded by the Swedish government.

[email protected]

SOURCE: Jönsson TS et al. Osteoarthritis Cartilage. 2019 Apr;27(suppl 1):S497, Abstract 717.

TORONTO – Osteoarthritis research doesn’t get nearly the respect it deserves in the medical literature, Elizabeth M. Badley, PhD, asserted at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Osteoarthritis is by far the most common type of arthritis. There are easily 10 times more people who have osteoarthritis than any other joint disease, but when you look at the literature, the situation is kind of reversed. Osteoarthritis is brushed off by society to a degree,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Bradley and colleagues performed a search of MEDLINE for 2007-2016, which turned up a total of 1,625 publications in 2016 on osteoarthritis, excluding those with an orthopedic surgery focus, compared with 10,904 results regarding the broader topic of joint diseases and 28,932 on musculoskeletal diseases.

The bottom line: “Progress is slow, and at this rate osteoarthritis will not be receiving the attention it deserves in our lifetime,” said Dr. Badley, of the department of epidemiology at the University of Toronto and a senior scientist at the Krembil Research Institute, also in Toronto.

The number of publications per year devoted to OA rose by a robust 88% during 2007-2016, while the number on OA not focused on orthopedic procedures grew by 65%. Both of these increases were greater than those for publications on musculoskeletal diseases and joint diseases overall, which were 41% and 51%, respectively. But the absolute number of OA publications was dwarfed by the numbers of those in the other search categories. For example, the number of publications on OA without an orthopedic surgery thrust was 985 in 2007, compared with 7,204 on joint diseases overall.

Among the striking findings of the investigators’ study of the medical literature was the disconnect between the amount of attention devoted to some of the joint-specific manifestations of OA and the actual prevalence of these conditions in the population. For example, the prevalence of hand OA in people living with OA was 52% according to the 2009 Survey on Living with Chronic Diseases in Canada, conducted by Statistics Canada, yet only 6.5% of the publications on OA in 2016 were devoted to hand/thumb OA. Similarly, the prevalence of spine OA was 52% among Canadians with OA, but only 4.3% of OA publications in 2016 focused on that topic. And while the number of publications devoted to elbow OA soared by a seemingly impressive 233% during the study period, the actual numbers were 3 publications in 2007 and 10 in 2016.

“Also, the average number of affected joints in people with osteoarthritis is four. Yet very, very few papers are about multijoint osteoarthritis. And when they do talk about multijoint osteoarthritis, they’re still only talking about hand/hip/knee. So we’re missing the bigger picture of osteoarthritis as a multijoint disease. We’re missing the spine, largely, as a part of osteoarthritis, and we’re missing the peripheral joints,” she said.

Dr. Badley reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Badley EM et al. Osteoarthritis Cartilage. 2019 Apr;27(Suppl 1):S278, Abstract 393.

TORONTO – Osteoarthritis research doesn’t get nearly the respect it deserves in the medical literature, Elizabeth M. Badley, PhD, asserted at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Osteoarthritis is by far the most common type of arthritis. There are easily 10 times more people who have osteoarthritis than any other joint disease, but when you look at the literature, the situation is kind of reversed. Osteoarthritis is brushed off by society to a degree,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Bradley and colleagues performed a search of MEDLINE for 2007-2016, which turned up a total of 1,625 publications in 2016 on osteoarthritis, excluding those with an orthopedic surgery focus, compared with 10,904 results regarding the broader topic of joint diseases and 28,932 on musculoskeletal diseases.

The bottom line: “Progress is slow, and at this rate osteoarthritis will not be receiving the attention it deserves in our lifetime,” said Dr. Badley, of the department of epidemiology at the University of Toronto and a senior scientist at the Krembil Research Institute, also in Toronto.

The number of publications per year devoted to OA rose by a robust 88% during 2007-2016, while the number on OA not focused on orthopedic procedures grew by 65%. Both of these increases were greater than those for publications on musculoskeletal diseases and joint diseases overall, which were 41% and 51%, respectively. But the absolute number of OA publications was dwarfed by the numbers of those in the other search categories. For example, the number of publications on OA without an orthopedic surgery thrust was 985 in 2007, compared with 7,204 on joint diseases overall.

Among the striking findings of the investigators’ study of the medical literature was the disconnect between the amount of attention devoted to some of the joint-specific manifestations of OA and the actual prevalence of these conditions in the population. For example, the prevalence of hand OA in people living with OA was 52% according to the 2009 Survey on Living with Chronic Diseases in Canada, conducted by Statistics Canada, yet only 6.5% of the publications on OA in 2016 were devoted to hand/thumb OA. Similarly, the prevalence of spine OA was 52% among Canadians with OA, but only 4.3% of OA publications in 2016 focused on that topic. And while the number of publications devoted to elbow OA soared by a seemingly impressive 233% during the study period, the actual numbers were 3 publications in 2007 and 10 in 2016.

“Also, the average number of affected joints in people with osteoarthritis is four. Yet very, very few papers are about multijoint osteoarthritis. And when they do talk about multijoint osteoarthritis, they’re still only talking about hand/hip/knee. So we’re missing the bigger picture of osteoarthritis as a multijoint disease. We’re missing the spine, largely, as a part of osteoarthritis, and we’re missing the peripheral joints,” she said.

Dr. Badley reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Badley EM et al. Osteoarthritis Cartilage. 2019 Apr;27(Suppl 1):S278, Abstract 393.

TORONTO – Osteoarthritis research doesn’t get nearly the respect it deserves in the medical literature, Elizabeth M. Badley, PhD, asserted at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Osteoarthritis is by far the most common type of arthritis. There are easily 10 times more people who have osteoarthritis than any other joint disease, but when you look at the literature, the situation is kind of reversed. Osteoarthritis is brushed off by society to a degree,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Bradley and colleagues performed a search of MEDLINE for 2007-2016, which turned up a total of 1,625 publications in 2016 on osteoarthritis, excluding those with an orthopedic surgery focus, compared with 10,904 results regarding the broader topic of joint diseases and 28,932 on musculoskeletal diseases.

The bottom line: “Progress is slow, and at this rate osteoarthritis will not be receiving the attention it deserves in our lifetime,” said Dr. Badley, of the department of epidemiology at the University of Toronto and a senior scientist at the Krembil Research Institute, also in Toronto.

The number of publications per year devoted to OA rose by a robust 88% during 2007-2016, while the number on OA not focused on orthopedic procedures grew by 65%. Both of these increases were greater than those for publications on musculoskeletal diseases and joint diseases overall, which were 41% and 51%, respectively. But the absolute number of OA publications was dwarfed by the numbers of those in the other search categories. For example, the number of publications on OA without an orthopedic surgery thrust was 985 in 2007, compared with 7,204 on joint diseases overall.

Among the striking findings of the investigators’ study of the medical literature was the disconnect between the amount of attention devoted to some of the joint-specific manifestations of OA and the actual prevalence of these conditions in the population. For example, the prevalence of hand OA in people living with OA was 52% according to the 2009 Survey on Living with Chronic Diseases in Canada, conducted by Statistics Canada, yet only 6.5% of the publications on OA in 2016 were devoted to hand/thumb OA. Similarly, the prevalence of spine OA was 52% among Canadians with OA, but only 4.3% of OA publications in 2016 focused on that topic. And while the number of publications devoted to elbow OA soared by a seemingly impressive 233% during the study period, the actual numbers were 3 publications in 2007 and 10 in 2016.

“Also, the average number of affected joints in people with osteoarthritis is four. Yet very, very few papers are about multijoint osteoarthritis. And when they do talk about multijoint osteoarthritis, they’re still only talking about hand/hip/knee. So we’re missing the bigger picture of osteoarthritis as a multijoint disease. We’re missing the spine, largely, as a part of osteoarthritis, and we’re missing the peripheral joints,” she said.

Dr. Badley reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Badley EM et al. Osteoarthritis Cartilage. 2019 Apr;27(Suppl 1):S278, Abstract 393.