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Jeff Evans has been editor of Rheumatology News/MDedge Rheumatology and the EULAR Congress News since 2013. He started at Frontline Medical Communications in 2001 and was a reporter for 8 years before serving as editor of Clinical Neurology News and World Neurology, and briefly as editor of GI & Hepatology News. He graduated cum laude from Cornell University (New York) with a BA in biological sciences, concentrating in neurobiology and behavior.
Fiber may play role in lessening knee pain, OA development
Consumption of dietary fiber at the recommended average intake of 25 g per day was associated with lower risks of developing symptomatic knee osteoarthritis and moderate or severe knee pain over 4-8 years in two separate analyses of Osteoarthritis Initiative participants conducted by investigators at Boston University.
The studies are the first to describe an association between total dietary fiber and lower risk of symptomatic OA and pain worsening in the knee, as well as a lower risk of moderate and severe pain patterns. The lowered risks were partially mediated by body mass index (BMI) but persisted even after adjustment for the variable.
In both studies, the investigators estimated dietary fiber intake by using a validated food frequency questionnaire at baseline that summed the fibers from grains, fruits and vegetables, and nuts and legumes.
Fiber and symptomatic knee OA
At the end of 4 years of follow-up, Dr. Dai and her colleagues identified 152 knees with incident radiographic OA (defined as a knee newly developing a Kellgren and Lawrence grade of 2 or higher), 869 knees with incident symptomatic OA (defined as new onset of both radiographic OA and a painful knee on most days in past month), and 1,964 knees with pain worsening as defined by an increase of at least 14% of the baseline Western Ontario and McMaster Universities (WOMAC) Index pain subscale score at each annual exam. This analysis excluded 540 people who were lost to follow-up and 205 who had invalid caloric intake recordings, leaving 4,051 in the study. The outcomes also excluded people with prevalent radiographic or symptomatic knee OA or knee pain worsening at baseline.
There was a significant trend for lower risk of both symptomatic OA (P less than .002) and pain worsening (P = .005) across four quartiles of daily total dietary fiber intake (mean of 9.1 g, 13 g, 16 g, and 21.9 g in quartiles 1-4). Quartile 4 daily intake was associated with a statistically significant 30% reduction (95% confidence interval, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening. Both comparisons were adjusted for age, sex, race, total energy intake, education, smoking status, physical activity, intake of other dietary factors (including polyunsaturated fat and other fats, vitamin C, vitamin D, vitamin E, vitamin K, dairy products, sweets, and soda), and nonsteroidal anti-inflammatory drug use (for the pain-worsening comparison).
Even though approximately 34% of the association between total fiber intake and symptomatic OA and 22% of the association between total fiber intake and pain worsening were mediated through reduced BMI, further adjustment of the comparisons for baseline BMI yielded similarly significant results.
The investigators found no associations between total dietary fiber intake and radiographic knee OA or for other fiber intake with either symptomatic or radiographic knee OA.
“The strongest protection was suggested at the highest quartile, which is in line with the current dietary guidelines for daily fiber intake. For older people [aged 51 years and older], for women it’s 22 g per day and for men it’s 28 g per day,” Dr. Dai said at the meeting.
Fiber and knee pain trajectories
Dr. Dai and her associates identified distinct, relatively homogeneous clusters of WOMAC pain trajectories over the 8-year study course in patients with and without radiographic knee OA at baseline in the Arthritis Care & Research study, and then examined their relationship to participants’ total dietary fiber intake, divided into quartiles (Arthritis Res Care. 2016; Nov 29. doi: 10.1002/acr.23158). The investigators found four pain trajectory patterns, including no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%).
Individuals who consumed the most total fiber also had the highest representation in the no pain pattern (38.1%) and the lowest representation in the severe pain pattern (4.3%). A high total fiber intake was associated with lower risk of having a moderate or severe pain pattern when compared with those in the no pain trajectory (both P for trend less than .01). Intake of fiber in the highest quartile was associated with a 24% lower likelihood (95% CI, 7%-39%) of belonging to the moderate pain pattern and a 44% lower likelihood (95% CI, 2%-59%) of being in the severe pain pattern, compared with individuals in the lowest intake quartile.
The same four pain trajectory patterns existed in individuals with radiographic knee OA at baseline, but the proportions were shifted slightly lower for no pain (26.1%) and higher for severe pain (7.9%). There was an even greater effect magnitude for the association between dietary total fiber and moderate or severe pain pattern among individuals with radiographic knee OA at baseline. Similar results were found for participants without radiographic knee OA at baseline. The relationships between total dietary fiber intake and pain patterns were somewhat attenuated after adjustment for depression scores and BMI at baseline but still remained statistically significant.
In each of the comparisons and sensitivity analyses, the highest quartile of cereal grain fiber intake was also significant on its own in lowering risk for being in the moderate or severe pain trajectory patterns. However, no significant results were found for fiber from fruits and vegetables or from nuts and legumes.
The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
Consumption of dietary fiber at the recommended average intake of 25 g per day was associated with lower risks of developing symptomatic knee osteoarthritis and moderate or severe knee pain over 4-8 years in two separate analyses of Osteoarthritis Initiative participants conducted by investigators at Boston University.
The studies are the first to describe an association between total dietary fiber and lower risk of symptomatic OA and pain worsening in the knee, as well as a lower risk of moderate and severe pain patterns. The lowered risks were partially mediated by body mass index (BMI) but persisted even after adjustment for the variable.
In both studies, the investigators estimated dietary fiber intake by using a validated food frequency questionnaire at baseline that summed the fibers from grains, fruits and vegetables, and nuts and legumes.
Fiber and symptomatic knee OA
At the end of 4 years of follow-up, Dr. Dai and her colleagues identified 152 knees with incident radiographic OA (defined as a knee newly developing a Kellgren and Lawrence grade of 2 or higher), 869 knees with incident symptomatic OA (defined as new onset of both radiographic OA and a painful knee on most days in past month), and 1,964 knees with pain worsening as defined by an increase of at least 14% of the baseline Western Ontario and McMaster Universities (WOMAC) Index pain subscale score at each annual exam. This analysis excluded 540 people who were lost to follow-up and 205 who had invalid caloric intake recordings, leaving 4,051 in the study. The outcomes also excluded people with prevalent radiographic or symptomatic knee OA or knee pain worsening at baseline.
There was a significant trend for lower risk of both symptomatic OA (P less than .002) and pain worsening (P = .005) across four quartiles of daily total dietary fiber intake (mean of 9.1 g, 13 g, 16 g, and 21.9 g in quartiles 1-4). Quartile 4 daily intake was associated with a statistically significant 30% reduction (95% confidence interval, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening. Both comparisons were adjusted for age, sex, race, total energy intake, education, smoking status, physical activity, intake of other dietary factors (including polyunsaturated fat and other fats, vitamin C, vitamin D, vitamin E, vitamin K, dairy products, sweets, and soda), and nonsteroidal anti-inflammatory drug use (for the pain-worsening comparison).
Even though approximately 34% of the association between total fiber intake and symptomatic OA and 22% of the association between total fiber intake and pain worsening were mediated through reduced BMI, further adjustment of the comparisons for baseline BMI yielded similarly significant results.
The investigators found no associations between total dietary fiber intake and radiographic knee OA or for other fiber intake with either symptomatic or radiographic knee OA.
“The strongest protection was suggested at the highest quartile, which is in line with the current dietary guidelines for daily fiber intake. For older people [aged 51 years and older], for women it’s 22 g per day and for men it’s 28 g per day,” Dr. Dai said at the meeting.
Fiber and knee pain trajectories
Dr. Dai and her associates identified distinct, relatively homogeneous clusters of WOMAC pain trajectories over the 8-year study course in patients with and without radiographic knee OA at baseline in the Arthritis Care & Research study, and then examined their relationship to participants’ total dietary fiber intake, divided into quartiles (Arthritis Res Care. 2016; Nov 29. doi: 10.1002/acr.23158). The investigators found four pain trajectory patterns, including no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%).
Individuals who consumed the most total fiber also had the highest representation in the no pain pattern (38.1%) and the lowest representation in the severe pain pattern (4.3%). A high total fiber intake was associated with lower risk of having a moderate or severe pain pattern when compared with those in the no pain trajectory (both P for trend less than .01). Intake of fiber in the highest quartile was associated with a 24% lower likelihood (95% CI, 7%-39%) of belonging to the moderate pain pattern and a 44% lower likelihood (95% CI, 2%-59%) of being in the severe pain pattern, compared with individuals in the lowest intake quartile.
The same four pain trajectory patterns existed in individuals with radiographic knee OA at baseline, but the proportions were shifted slightly lower for no pain (26.1%) and higher for severe pain (7.9%). There was an even greater effect magnitude for the association between dietary total fiber and moderate or severe pain pattern among individuals with radiographic knee OA at baseline. Similar results were found for participants without radiographic knee OA at baseline. The relationships between total dietary fiber intake and pain patterns were somewhat attenuated after adjustment for depression scores and BMI at baseline but still remained statistically significant.
In each of the comparisons and sensitivity analyses, the highest quartile of cereal grain fiber intake was also significant on its own in lowering risk for being in the moderate or severe pain trajectory patterns. However, no significant results were found for fiber from fruits and vegetables or from nuts and legumes.
The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
Consumption of dietary fiber at the recommended average intake of 25 g per day was associated with lower risks of developing symptomatic knee osteoarthritis and moderate or severe knee pain over 4-8 years in two separate analyses of Osteoarthritis Initiative participants conducted by investigators at Boston University.
The studies are the first to describe an association between total dietary fiber and lower risk of symptomatic OA and pain worsening in the knee, as well as a lower risk of moderate and severe pain patterns. The lowered risks were partially mediated by body mass index (BMI) but persisted even after adjustment for the variable.
In both studies, the investigators estimated dietary fiber intake by using a validated food frequency questionnaire at baseline that summed the fibers from grains, fruits and vegetables, and nuts and legumes.
Fiber and symptomatic knee OA
At the end of 4 years of follow-up, Dr. Dai and her colleagues identified 152 knees with incident radiographic OA (defined as a knee newly developing a Kellgren and Lawrence grade of 2 or higher), 869 knees with incident symptomatic OA (defined as new onset of both radiographic OA and a painful knee on most days in past month), and 1,964 knees with pain worsening as defined by an increase of at least 14% of the baseline Western Ontario and McMaster Universities (WOMAC) Index pain subscale score at each annual exam. This analysis excluded 540 people who were lost to follow-up and 205 who had invalid caloric intake recordings, leaving 4,051 in the study. The outcomes also excluded people with prevalent radiographic or symptomatic knee OA or knee pain worsening at baseline.
There was a significant trend for lower risk of both symptomatic OA (P less than .002) and pain worsening (P = .005) across four quartiles of daily total dietary fiber intake (mean of 9.1 g, 13 g, 16 g, and 21.9 g in quartiles 1-4). Quartile 4 daily intake was associated with a statistically significant 30% reduction (95% confidence interval, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening. Both comparisons were adjusted for age, sex, race, total energy intake, education, smoking status, physical activity, intake of other dietary factors (including polyunsaturated fat and other fats, vitamin C, vitamin D, vitamin E, vitamin K, dairy products, sweets, and soda), and nonsteroidal anti-inflammatory drug use (for the pain-worsening comparison).
Even though approximately 34% of the association between total fiber intake and symptomatic OA and 22% of the association between total fiber intake and pain worsening were mediated through reduced BMI, further adjustment of the comparisons for baseline BMI yielded similarly significant results.
The investigators found no associations between total dietary fiber intake and radiographic knee OA or for other fiber intake with either symptomatic or radiographic knee OA.
“The strongest protection was suggested at the highest quartile, which is in line with the current dietary guidelines for daily fiber intake. For older people [aged 51 years and older], for women it’s 22 g per day and for men it’s 28 g per day,” Dr. Dai said at the meeting.
Fiber and knee pain trajectories
Dr. Dai and her associates identified distinct, relatively homogeneous clusters of WOMAC pain trajectories over the 8-year study course in patients with and without radiographic knee OA at baseline in the Arthritis Care & Research study, and then examined their relationship to participants’ total dietary fiber intake, divided into quartiles (Arthritis Res Care. 2016; Nov 29. doi: 10.1002/acr.23158). The investigators found four pain trajectory patterns, including no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%).
Individuals who consumed the most total fiber also had the highest representation in the no pain pattern (38.1%) and the lowest representation in the severe pain pattern (4.3%). A high total fiber intake was associated with lower risk of having a moderate or severe pain pattern when compared with those in the no pain trajectory (both P for trend less than .01). Intake of fiber in the highest quartile was associated with a 24% lower likelihood (95% CI, 7%-39%) of belonging to the moderate pain pattern and a 44% lower likelihood (95% CI, 2%-59%) of being in the severe pain pattern, compared with individuals in the lowest intake quartile.
The same four pain trajectory patterns existed in individuals with radiographic knee OA at baseline, but the proportions were shifted slightly lower for no pain (26.1%) and higher for severe pain (7.9%). There was an even greater effect magnitude for the association between dietary total fiber and moderate or severe pain pattern among individuals with radiographic knee OA at baseline. Similar results were found for participants without radiographic knee OA at baseline. The relationships between total dietary fiber intake and pain patterns were somewhat attenuated after adjustment for depression scores and BMI at baseline but still remained statistically significant.
In each of the comparisons and sensitivity analyses, the highest quartile of cereal grain fiber intake was also significant on its own in lowering risk for being in the moderate or severe pain trajectory patterns. However, no significant results were found for fiber from fruits and vegetables or from nuts and legumes.
The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
FROM ARTHRITIS CARE & RESEARCH AND THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The highest quartile of daily dietary fiber intake was associated with a statistically significant 30% reduction (95% CI, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening.
Data source: Two analyses of the prospective, multicenter Osteoarthritis Initiative cohort of 4,796 men and women aged 45-79 years with or at risk for knee osteoarthritis.
Disclosures: The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
Infliximab biosimilar posts mostly reassuring data in Norway’s NOR-SWITCH study
WASHINGTON – Data from the first randomized trial of switching from an originator biologic to a biosimilar of the originator indicate that the infliximab biosimilar Remsima is no different from the infliximab originator Remicade in the rate of disease worsening over 1 year across a combination of all its approved indications.
The outcomes of the Norwegian, double-blind, noninferiority trial, called NOR-SWITCH, indicate similar rates of disease worsening across patients switched to Remsima and those who stayed on Remicade. However, exploratory group analyses conducted on the different disease subgroups in the trial (Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis) showed a potentially concerning level of disease worsening among Crohn’s disease patients on Remsima with a confidence interval that nearly fell entirely within the range favoring Remicade.
In the United States, Remsima, also known as CT-P13, is marketed by Pfizer as Inflectra.
The trial randomized 482 patients who were on stable treatment with Remicade for at least 6 months for any of the six indications for which Remicade and Remsima are approved to either stay on Remicade or switch to Remsima with the same dosing regimen for 52 weeks. Overall, patients had a mean age of about 48 years and 36%-41% were female. They had a mean disease duration of about 17 years and had been taking Remicade for a mean of nearly 7 years.
The primary endpoint was disease worsening during follow-up, according to worsening in disease-specific composite measures and/or a consensus between an investigator and a patient that led to a major change in treatment. The investigators made an assumption of 30% disease worsening across all the indications for the trial’s power calculation, based on available literature and observational data.
Disease worsening occurred in 26.2% of patients who stayed on Remicade and 29.6% of patients who switched to Remsima, based on a per-protocol analysis of 202 Remicade and 206 Remsima patients. The 95% confidence interval of the adjusted treatment difference of –4.4% was –12.7% to 3.9%, which was within the pre-specified noninferiority margin of 15%.
Exploratory subgroup analyses of the different disease subgroups showed no statistically significant differences between the two treatments in disease worsening. However, in Crohn’s disease patients, who formed the largest subgroup in the study at 155 patients, the adjusted treatment difference was –14.3% (21.2% with disease worsening for Remicade and 36.5% for Remsima) with a 95% CI of –29.3% to 0.7%.
It’s difficult to discern whether the 95% confidence interval seen in the Crohn’s disease subgroup is a part of the natural variation one would expect to see in a subgroup analysis of different diseases or if there might be a true signal for disease worsening in the Crohn’s disease patients who took Remsima. “The problem is that it’s in the largest subgroup that has no other data. If this had been in rheumatoid arthritis, that would be different,” coauthor Inge C. Olsen, PhD, a biostatistician at Diakonhjemmet Hospital, said in an interview. “All the registry trials were done in RA and spondyloarthritis patients. ... That’s an issue, but with regards to the [NOR-SWITCH] study, it’s very clear that you have no power to show anything in the subgroup analysis, and they are exploratory analyses and are not answering any hypothesis.” Currently, there are no plans to follow up on these results in another study, he said.
Other issues that the NOR-SWITCH study does not answer are the outcomes of switching back and forth between Remicade and Remsima, switching from one infliximab biosimilar to another infliximab biosimilar, and switching from other originator biologics to their biosimilars.
“Is that feasible? Is that safe? Will it retain efficacy? We don’t know. There’s a real need for those studies to be done,” Dr. Goll said.
In Norway, the remaining patients who had not switched yet from Remicade to Remsima are now doing so based on the trial’s results, Dr. Goll said. The cost of Remsima in Norway was about 75% less than Remicade in 2015 and about 60% less in 2016, she noted.
It’s still an open question what the results of the NOR-SWITCH trial might indicate for how clinicians in the United States will use Inflectra and other biosimilars, according to John J. Cush, MD, professor of medicine and rheumatology at Baylor University, Dallas.
“I think the real problem here is that it’s nice to know that [CT-P13] wasn’t inferior, but when you get into the weeds and you look at the details, those of us who may not have a lot of certainty about this might worry about this, especially when there are three new biosimilars approved in the United States: Amjevita, which is an adalimumab biosimilar; Erelzi, which is an etanercept biosimilar; and Inflectra’s about to be launched as an infliximab biosimilar,” Dr. Cush said during a session reviewing selected abstracts from the meeting. “When this NOR-SWITCH study was done in Norway, it’s a 70% savings over the original product. The new ones being introduced over here [in the United States] start at about 15%. I’m less motivated with that degree of savings to want to take some chances on my patients. So we need a little bit more certainty; we need to feel better about the cost savings to patients and health care overall. Confidence in biosimilars is what’s going to sell biosimilars. We’re a long way from confidence still.”
NOR-SWITCH was funded by the Norwegian government. Some of the investigators disclosed relationships with Pfizer and/or Celltrion, which separately market CT-P13 in different parts of the world.
[email protected]
WASHINGTON – Data from the first randomized trial of switching from an originator biologic to a biosimilar of the originator indicate that the infliximab biosimilar Remsima is no different from the infliximab originator Remicade in the rate of disease worsening over 1 year across a combination of all its approved indications.
The outcomes of the Norwegian, double-blind, noninferiority trial, called NOR-SWITCH, indicate similar rates of disease worsening across patients switched to Remsima and those who stayed on Remicade. However, exploratory group analyses conducted on the different disease subgroups in the trial (Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis) showed a potentially concerning level of disease worsening among Crohn’s disease patients on Remsima with a confidence interval that nearly fell entirely within the range favoring Remicade.
In the United States, Remsima, also known as CT-P13, is marketed by Pfizer as Inflectra.
The trial randomized 482 patients who were on stable treatment with Remicade for at least 6 months for any of the six indications for which Remicade and Remsima are approved to either stay on Remicade or switch to Remsima with the same dosing regimen for 52 weeks. Overall, patients had a mean age of about 48 years and 36%-41% were female. They had a mean disease duration of about 17 years and had been taking Remicade for a mean of nearly 7 years.
The primary endpoint was disease worsening during follow-up, according to worsening in disease-specific composite measures and/or a consensus between an investigator and a patient that led to a major change in treatment. The investigators made an assumption of 30% disease worsening across all the indications for the trial’s power calculation, based on available literature and observational data.
Disease worsening occurred in 26.2% of patients who stayed on Remicade and 29.6% of patients who switched to Remsima, based on a per-protocol analysis of 202 Remicade and 206 Remsima patients. The 95% confidence interval of the adjusted treatment difference of –4.4% was –12.7% to 3.9%, which was within the pre-specified noninferiority margin of 15%.
Exploratory subgroup analyses of the different disease subgroups showed no statistically significant differences between the two treatments in disease worsening. However, in Crohn’s disease patients, who formed the largest subgroup in the study at 155 patients, the adjusted treatment difference was –14.3% (21.2% with disease worsening for Remicade and 36.5% for Remsima) with a 95% CI of –29.3% to 0.7%.
It’s difficult to discern whether the 95% confidence interval seen in the Crohn’s disease subgroup is a part of the natural variation one would expect to see in a subgroup analysis of different diseases or if there might be a true signal for disease worsening in the Crohn’s disease patients who took Remsima. “The problem is that it’s in the largest subgroup that has no other data. If this had been in rheumatoid arthritis, that would be different,” coauthor Inge C. Olsen, PhD, a biostatistician at Diakonhjemmet Hospital, said in an interview. “All the registry trials were done in RA and spondyloarthritis patients. ... That’s an issue, but with regards to the [NOR-SWITCH] study, it’s very clear that you have no power to show anything in the subgroup analysis, and they are exploratory analyses and are not answering any hypothesis.” Currently, there are no plans to follow up on these results in another study, he said.
Other issues that the NOR-SWITCH study does not answer are the outcomes of switching back and forth between Remicade and Remsima, switching from one infliximab biosimilar to another infliximab biosimilar, and switching from other originator biologics to their biosimilars.
“Is that feasible? Is that safe? Will it retain efficacy? We don’t know. There’s a real need for those studies to be done,” Dr. Goll said.
In Norway, the remaining patients who had not switched yet from Remicade to Remsima are now doing so based on the trial’s results, Dr. Goll said. The cost of Remsima in Norway was about 75% less than Remicade in 2015 and about 60% less in 2016, she noted.
It’s still an open question what the results of the NOR-SWITCH trial might indicate for how clinicians in the United States will use Inflectra and other biosimilars, according to John J. Cush, MD, professor of medicine and rheumatology at Baylor University, Dallas.
“I think the real problem here is that it’s nice to know that [CT-P13] wasn’t inferior, but when you get into the weeds and you look at the details, those of us who may not have a lot of certainty about this might worry about this, especially when there are three new biosimilars approved in the United States: Amjevita, which is an adalimumab biosimilar; Erelzi, which is an etanercept biosimilar; and Inflectra’s about to be launched as an infliximab biosimilar,” Dr. Cush said during a session reviewing selected abstracts from the meeting. “When this NOR-SWITCH study was done in Norway, it’s a 70% savings over the original product. The new ones being introduced over here [in the United States] start at about 15%. I’m less motivated with that degree of savings to want to take some chances on my patients. So we need a little bit more certainty; we need to feel better about the cost savings to patients and health care overall. Confidence in biosimilars is what’s going to sell biosimilars. We’re a long way from confidence still.”
NOR-SWITCH was funded by the Norwegian government. Some of the investigators disclosed relationships with Pfizer and/or Celltrion, which separately market CT-P13 in different parts of the world.
[email protected]
WASHINGTON – Data from the first randomized trial of switching from an originator biologic to a biosimilar of the originator indicate that the infliximab biosimilar Remsima is no different from the infliximab originator Remicade in the rate of disease worsening over 1 year across a combination of all its approved indications.
The outcomes of the Norwegian, double-blind, noninferiority trial, called NOR-SWITCH, indicate similar rates of disease worsening across patients switched to Remsima and those who stayed on Remicade. However, exploratory group analyses conducted on the different disease subgroups in the trial (Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis) showed a potentially concerning level of disease worsening among Crohn’s disease patients on Remsima with a confidence interval that nearly fell entirely within the range favoring Remicade.
In the United States, Remsima, also known as CT-P13, is marketed by Pfizer as Inflectra.
The trial randomized 482 patients who were on stable treatment with Remicade for at least 6 months for any of the six indications for which Remicade and Remsima are approved to either stay on Remicade or switch to Remsima with the same dosing regimen for 52 weeks. Overall, patients had a mean age of about 48 years and 36%-41% were female. They had a mean disease duration of about 17 years and had been taking Remicade for a mean of nearly 7 years.
The primary endpoint was disease worsening during follow-up, according to worsening in disease-specific composite measures and/or a consensus between an investigator and a patient that led to a major change in treatment. The investigators made an assumption of 30% disease worsening across all the indications for the trial’s power calculation, based on available literature and observational data.
Disease worsening occurred in 26.2% of patients who stayed on Remicade and 29.6% of patients who switched to Remsima, based on a per-protocol analysis of 202 Remicade and 206 Remsima patients. The 95% confidence interval of the adjusted treatment difference of –4.4% was –12.7% to 3.9%, which was within the pre-specified noninferiority margin of 15%.
Exploratory subgroup analyses of the different disease subgroups showed no statistically significant differences between the two treatments in disease worsening. However, in Crohn’s disease patients, who formed the largest subgroup in the study at 155 patients, the adjusted treatment difference was –14.3% (21.2% with disease worsening for Remicade and 36.5% for Remsima) with a 95% CI of –29.3% to 0.7%.
It’s difficult to discern whether the 95% confidence interval seen in the Crohn’s disease subgroup is a part of the natural variation one would expect to see in a subgroup analysis of different diseases or if there might be a true signal for disease worsening in the Crohn’s disease patients who took Remsima. “The problem is that it’s in the largest subgroup that has no other data. If this had been in rheumatoid arthritis, that would be different,” coauthor Inge C. Olsen, PhD, a biostatistician at Diakonhjemmet Hospital, said in an interview. “All the registry trials were done in RA and spondyloarthritis patients. ... That’s an issue, but with regards to the [NOR-SWITCH] study, it’s very clear that you have no power to show anything in the subgroup analysis, and they are exploratory analyses and are not answering any hypothesis.” Currently, there are no plans to follow up on these results in another study, he said.
Other issues that the NOR-SWITCH study does not answer are the outcomes of switching back and forth between Remicade and Remsima, switching from one infliximab biosimilar to another infliximab biosimilar, and switching from other originator biologics to their biosimilars.
“Is that feasible? Is that safe? Will it retain efficacy? We don’t know. There’s a real need for those studies to be done,” Dr. Goll said.
In Norway, the remaining patients who had not switched yet from Remicade to Remsima are now doing so based on the trial’s results, Dr. Goll said. The cost of Remsima in Norway was about 75% less than Remicade in 2015 and about 60% less in 2016, she noted.
It’s still an open question what the results of the NOR-SWITCH trial might indicate for how clinicians in the United States will use Inflectra and other biosimilars, according to John J. Cush, MD, professor of medicine and rheumatology at Baylor University, Dallas.
“I think the real problem here is that it’s nice to know that [CT-P13] wasn’t inferior, but when you get into the weeds and you look at the details, those of us who may not have a lot of certainty about this might worry about this, especially when there are three new biosimilars approved in the United States: Amjevita, which is an adalimumab biosimilar; Erelzi, which is an etanercept biosimilar; and Inflectra’s about to be launched as an infliximab biosimilar,” Dr. Cush said during a session reviewing selected abstracts from the meeting. “When this NOR-SWITCH study was done in Norway, it’s a 70% savings over the original product. The new ones being introduced over here [in the United States] start at about 15%. I’m less motivated with that degree of savings to want to take some chances on my patients. So we need a little bit more certainty; we need to feel better about the cost savings to patients and health care overall. Confidence in biosimilars is what’s going to sell biosimilars. We’re a long way from confidence still.”
NOR-SWITCH was funded by the Norwegian government. Some of the investigators disclosed relationships with Pfizer and/or Celltrion, which separately market CT-P13 in different parts of the world.
[email protected]
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Disease worsening occurred in 26.2% of patients who stayed on Remicade and 29.6% of patients who switched to Remsima, based on a per-protocol analysis.
Data source: The multicenter, double-blind, randomized NOR-SWITCH trial of 482 patients.
Disclosures: The trial was funded by the Norwegian government. Some of the investigators disclosed relationships with Pfizer and/or Celltrion, which separately market CT-P13 in different parts of the world.
Rheumatology malpractice litigation investigated for first time
WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.
The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.
Rheumatologists accounted for one-third of all named defendants in the 20 cases, which constituted a convenience sample. They excluded 10 cases because of duplication or lack of relevance to rheumatology. They searched the online legal database WestLaw using the terms “rheumatology” and “medical malpractice” to find all state and federal jury verdicts and settlements related to rheumatology during 1985-2015. The 20 cases occurred in 10 states. The plaintiffs had a mean age of about 52 years, and 45% were female.
Plaintiffs in the medical malpractice suits won only four of the cases, but those had a mean payout of about $2.78 million, which Mr. Prabhu described as lower than what’s been reported in other specialties that he and his colleagues are investigating, such as oncology and neurosurgery. The jury found in favor of the defendant in 12 of the cases, and in 3 cases the parties reached a settlement in which most payouts were not disclosed. The verdict was undisclosed in one case.
Mr. Prabhu said that the investigators discovered an additional 34 cases in their search of the database that they plan on characterizing in another study.
The researchers reported having no relevant financial disclosures.
WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.
The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.
Rheumatologists accounted for one-third of all named defendants in the 20 cases, which constituted a convenience sample. They excluded 10 cases because of duplication or lack of relevance to rheumatology. They searched the online legal database WestLaw using the terms “rheumatology” and “medical malpractice” to find all state and federal jury verdicts and settlements related to rheumatology during 1985-2015. The 20 cases occurred in 10 states. The plaintiffs had a mean age of about 52 years, and 45% were female.
Plaintiffs in the medical malpractice suits won only four of the cases, but those had a mean payout of about $2.78 million, which Mr. Prabhu described as lower than what’s been reported in other specialties that he and his colleagues are investigating, such as oncology and neurosurgery. The jury found in favor of the defendant in 12 of the cases, and in 3 cases the parties reached a settlement in which most payouts were not disclosed. The verdict was undisclosed in one case.
Mr. Prabhu said that the investigators discovered an additional 34 cases in their search of the database that they plan on characterizing in another study.
The researchers reported having no relevant financial disclosures.
WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.
The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.
Rheumatologists accounted for one-third of all named defendants in the 20 cases, which constituted a convenience sample. They excluded 10 cases because of duplication or lack of relevance to rheumatology. They searched the online legal database WestLaw using the terms “rheumatology” and “medical malpractice” to find all state and federal jury verdicts and settlements related to rheumatology during 1985-2015. The 20 cases occurred in 10 states. The plaintiffs had a mean age of about 52 years, and 45% were female.
Plaintiffs in the medical malpractice suits won only four of the cases, but those had a mean payout of about $2.78 million, which Mr. Prabhu described as lower than what’s been reported in other specialties that he and his colleagues are investigating, such as oncology and neurosurgery. The jury found in favor of the defendant in 12 of the cases, and in 3 cases the parties reached a settlement in which most payouts were not disclosed. The verdict was undisclosed in one case.
Mr. Prabhu said that the investigators discovered an additional 34 cases in their search of the database that they plan on characterizing in another study.
The researchers reported having no relevant financial disclosures.
Key clinical point:
Major finding: Plaintiffs in the malpractice suits won only 20% of the cases, but those had a mean payout of about $2.78 million.
Data source: A retrospective study of 20 rheumatic disease malpractice cases occurring in 1985-2015.
Disclosures: The researchers reported having no relevant financial disclosures.
OA progresses equally with new focal partial- or full-thickness cartilage damage
A small, partial-thickness focal cartilage defect in the tibiofemoral joint compartment has the same impact on osteoarthritis disease progression – defined as new cartilage damage – as does a full-thickness lesion, according to an analysis of data from the Multicenter Osteoarthritis Study.
Ali Guermazi, MD, PhD, of Boston University, and his associates used MRI to show that both full- and partial-thickness small focal defects (less than 1 cm) in the tibiofemoral compartment contributed significantly to the risk of incident cartilage damage 30 months later in other tibiofemoral compartment subregions (adjusted odds ratio, 1.62; 95% confidence interval, 1.06-2.47, for partial-thickness defects and aOR, 1.92; 95% CI, 1.00-3.66, for full-thickness defects) when compared with subregions with no baseline cartilage damage, defined as a Kellgren-Lawrence grade of 0-1.
The results indicate that “partial-thickness and full-thickness defects are similarly relevant in regard to cartilage damage development in knee osteoarthritis,” the investigators wrote.
They studied 374 compartments (359 knees), of which 140 knees (39%) had radiographic osteoarthritis defined as a Kellgren-Lawrence grade of 2 or higher).
“It is potentially important to detect focal cartilage defects early as there are various options for repair of focal cartilage defects ... [and it could be possible to use MRI] to screen persons with early-stage osteoarthritis or those at high risk of osteoarthritis and initiate treatment for focal cartilage defects,” they wrote.
Read the full study in Arthritis & Rheumatology (2016 Oct 27. doi: 10.1002/art.39970).
A small, partial-thickness focal cartilage defect in the tibiofemoral joint compartment has the same impact on osteoarthritis disease progression – defined as new cartilage damage – as does a full-thickness lesion, according to an analysis of data from the Multicenter Osteoarthritis Study.
Ali Guermazi, MD, PhD, of Boston University, and his associates used MRI to show that both full- and partial-thickness small focal defects (less than 1 cm) in the tibiofemoral compartment contributed significantly to the risk of incident cartilage damage 30 months later in other tibiofemoral compartment subregions (adjusted odds ratio, 1.62; 95% confidence interval, 1.06-2.47, for partial-thickness defects and aOR, 1.92; 95% CI, 1.00-3.66, for full-thickness defects) when compared with subregions with no baseline cartilage damage, defined as a Kellgren-Lawrence grade of 0-1.
The results indicate that “partial-thickness and full-thickness defects are similarly relevant in regard to cartilage damage development in knee osteoarthritis,” the investigators wrote.
They studied 374 compartments (359 knees), of which 140 knees (39%) had radiographic osteoarthritis defined as a Kellgren-Lawrence grade of 2 or higher).
“It is potentially important to detect focal cartilage defects early as there are various options for repair of focal cartilage defects ... [and it could be possible to use MRI] to screen persons with early-stage osteoarthritis or those at high risk of osteoarthritis and initiate treatment for focal cartilage defects,” they wrote.
Read the full study in Arthritis & Rheumatology (2016 Oct 27. doi: 10.1002/art.39970).
A small, partial-thickness focal cartilage defect in the tibiofemoral joint compartment has the same impact on osteoarthritis disease progression – defined as new cartilage damage – as does a full-thickness lesion, according to an analysis of data from the Multicenter Osteoarthritis Study.
Ali Guermazi, MD, PhD, of Boston University, and his associates used MRI to show that both full- and partial-thickness small focal defects (less than 1 cm) in the tibiofemoral compartment contributed significantly to the risk of incident cartilage damage 30 months later in other tibiofemoral compartment subregions (adjusted odds ratio, 1.62; 95% confidence interval, 1.06-2.47, for partial-thickness defects and aOR, 1.92; 95% CI, 1.00-3.66, for full-thickness defects) when compared with subregions with no baseline cartilage damage, defined as a Kellgren-Lawrence grade of 0-1.
The results indicate that “partial-thickness and full-thickness defects are similarly relevant in regard to cartilage damage development in knee osteoarthritis,” the investigators wrote.
They studied 374 compartments (359 knees), of which 140 knees (39%) had radiographic osteoarthritis defined as a Kellgren-Lawrence grade of 2 or higher).
“It is potentially important to detect focal cartilage defects early as there are various options for repair of focal cartilage defects ... [and it could be possible to use MRI] to screen persons with early-stage osteoarthritis or those at high risk of osteoarthritis and initiate treatment for focal cartilage defects,” they wrote.
Read the full study in Arthritis & Rheumatology (2016 Oct 27. doi: 10.1002/art.39970).
FROM ARTHRITIS & RHEUMATOLOGY
Shared medical appointment model shows potential for fibromyalgia patients
Fibromyalgia patients who participated in shared medical appointments staffed by an interdisciplinary team at a rural academic medical center reported high satisfaction with the new care model, according to Nicole M. Orzechowski, DO, and her colleagues in the department of rheumatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H.
The study of 67 referred patients, who were evaluated during a 1-year period with the shared medical appointment (SMA) model, revealed in post-session surveys that not only did all patients agree that the care model would assist in managing their condition, but 95% also thought that the peer-to-peer interaction was “extremely helpful.”
In the study, which Dr. Orzechowski will report at the annual meeting of the American College of Rheumatology in Washington, she and her associates noted that the 2.5-hour visits conducted by a rheumatologist, two nurse practitioners, a chaplain, and a secretary led to “clinical efficiency in assessing multiple new patients in a defined period of time,” improved wait times for fibromyalgia patients from 3 months to 1 month, and also freed up new patient consultation slots for other conditions. The investigators estimated that the SMA has generated an additional 113 work relative value units since its inception.
Prior to the SMA, each patient received a medical history questionnaire in the mail, and the investigators informed primary care physicians about the SMA and its format and asked them to perform specific labs if they had not been done already. Besides individual exams for confirming the diagnosis, measuring vital signs, and reconciling medications, the SMA consisted of a facilitated discussion by a trained chaplain, followed by a short presentation by the clinician (with time for discussion and questions), and then concluded with the chaplain’s demonstration of mindfulness techniques for managing chronic pain.
In the future, the investigators said that they hope to enhance and optimize the visit, expand its use, address referring provider satisfaction, and examine post-visit resource utilization.
None of the authors had disclosures to report.
Fibromyalgia patients who participated in shared medical appointments staffed by an interdisciplinary team at a rural academic medical center reported high satisfaction with the new care model, according to Nicole M. Orzechowski, DO, and her colleagues in the department of rheumatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H.
The study of 67 referred patients, who were evaluated during a 1-year period with the shared medical appointment (SMA) model, revealed in post-session surveys that not only did all patients agree that the care model would assist in managing their condition, but 95% also thought that the peer-to-peer interaction was “extremely helpful.”
In the study, which Dr. Orzechowski will report at the annual meeting of the American College of Rheumatology in Washington, she and her associates noted that the 2.5-hour visits conducted by a rheumatologist, two nurse practitioners, a chaplain, and a secretary led to “clinical efficiency in assessing multiple new patients in a defined period of time,” improved wait times for fibromyalgia patients from 3 months to 1 month, and also freed up new patient consultation slots for other conditions. The investigators estimated that the SMA has generated an additional 113 work relative value units since its inception.
Prior to the SMA, each patient received a medical history questionnaire in the mail, and the investigators informed primary care physicians about the SMA and its format and asked them to perform specific labs if they had not been done already. Besides individual exams for confirming the diagnosis, measuring vital signs, and reconciling medications, the SMA consisted of a facilitated discussion by a trained chaplain, followed by a short presentation by the clinician (with time for discussion and questions), and then concluded with the chaplain’s demonstration of mindfulness techniques for managing chronic pain.
In the future, the investigators said that they hope to enhance and optimize the visit, expand its use, address referring provider satisfaction, and examine post-visit resource utilization.
None of the authors had disclosures to report.
Fibromyalgia patients who participated in shared medical appointments staffed by an interdisciplinary team at a rural academic medical center reported high satisfaction with the new care model, according to Nicole M. Orzechowski, DO, and her colleagues in the department of rheumatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H.
The study of 67 referred patients, who were evaluated during a 1-year period with the shared medical appointment (SMA) model, revealed in post-session surveys that not only did all patients agree that the care model would assist in managing their condition, but 95% also thought that the peer-to-peer interaction was “extremely helpful.”
In the study, which Dr. Orzechowski will report at the annual meeting of the American College of Rheumatology in Washington, she and her associates noted that the 2.5-hour visits conducted by a rheumatologist, two nurse practitioners, a chaplain, and a secretary led to “clinical efficiency in assessing multiple new patients in a defined period of time,” improved wait times for fibromyalgia patients from 3 months to 1 month, and also freed up new patient consultation slots for other conditions. The investigators estimated that the SMA has generated an additional 113 work relative value units since its inception.
Prior to the SMA, each patient received a medical history questionnaire in the mail, and the investigators informed primary care physicians about the SMA and its format and asked them to perform specific labs if they had not been done already. Besides individual exams for confirming the diagnosis, measuring vital signs, and reconciling medications, the SMA consisted of a facilitated discussion by a trained chaplain, followed by a short presentation by the clinician (with time for discussion and questions), and then concluded with the chaplain’s demonstration of mindfulness techniques for managing chronic pain.
In the future, the investigators said that they hope to enhance and optimize the visit, expand its use, address referring provider satisfaction, and examine post-visit resource utilization.
None of the authors had disclosures to report.
FROM THE ACR ANNUAL MEETING
RA prevention trials seek to stop clinical onset of disease
Investigators across the United States and Europe hope to answer questions surrounding the feasibility of preventing rheumatoid arthritis in a series of proof-of-concept clinical trials that are enrolling patients with various risk factors for the disease. At least five trials have begun – with one already completed – to prevent RA with disease-modifying antirheumatic drugs, including a U.S. trial with hydroxychloroquine and European trials involving methotrexate, rituximab, and abatacept. Another trial with atorvastatin is also underway.
All of the trials involve participants with different risk factors for RA and may thereby provide a range of answers about where the most promising areas for disease prevention lie.
Hydroxychloroquine
Perhaps the broadest in scope of all the studies investigating the prevention of RA is the StopRA (Strategy to Prevent the Onset of Clinically Apparent Rheumatoid Arthritis) trial, which is randomizing 200 subjects with an anticyclic citrullinated peptide 3 (anti-CCP3) that’s greater than twice the normal level, with or without arthralgia, to either hydroxychloroquine (HCQ) 200-400 mg/day or placebo for 1 year, followed by 2 years of follow-up. Pilot data indicated that a level of 40 U/mL or higher of anti-CCP3, which is twice the normal level for positivity, gave a 50% chance of developing RA in the next 3 years regardless of symptoms, family history, or other factors.
The trial’s focus on people with an elevated level of anti-CCP3 limits it to just seropositive individuals, specifically those who are anti-citrullinated protein antibody (ACPA)-positive who constitute about 60%-70% of RA patients with established RA.
The investigators chose to use HCQ because it is a safe and well-tolerated medication for RA, and it may have mechanisms of action that may work particularly well in the early development of RA by blocking inflammation and epitope spreading, Dr. Deane said. “While hydroxychloroquine might not be powerful enough to stop active RA, we hypothesize that it’s just the right drug to block key processes early in its development,” Dr. Deane said in an interview, noting that HCQ is also used to block disease flares in palindromic rheumatism and diminish autoantibody responses in systemic lupus erythematosus.
The StopRA trial is being performed by the Autoimmunity Centers of Excellence, a network sponsored by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. Enrollment began at 18 U.S. sites in April 2016 with screening of first-degree relatives of patients with RA, community-based screening at health fairs, and finding CCP positive individuals without inflammatory arthritis in rheumatology clinics. The investigators estimate that they will need to screen 20,000 individuals to enroll 200 into the study. Dr. Deane said that he and his coinvestigators hope to use the variables that will arise from the diverse population to later determine subgroups who may respond best to the intervention. “We were concerned that if we made everybody too similar we wouldn’t be able to analyze whether symptoms or other factors mattered or not in who responded to the intervention. It may also allow us to catch some people at an early phase of their autoimmunity and others at a later phase and to determine for future studies when is the best time to intervene in preclinical RA with HCQ.”
It’s possible that HCQ will just delay RA rather than prevent it, Dr. Deane said, perhaps indicating that they may find that HCQ needs to be used longer. In any case, by the time the trial is completed in 2020 the investigators hope to gain rich natural history data to determine how to proceed in future trials, whether they use higher doses, longer-term dosing, or try a different target. In addition, the infrastructure of study sites established in StopRA should be incredibly valuable for future prevention studies.
“I envision a future where everybody is screened for RA risk using good blood tests and then given the opportunity for prevention,” first involving high-risk groups such as family members of people with RA, and then ultimately opening up to population-based screening because 90% of RA occurs in individuals without family history of the disease, Dr. Deane said. An analogy for this might be cardiovascular disease, he said, where we screen the cholesterol level of patients before they have had a heart attack, and if it’s above a certain threshold we prescribe a statin, healthy eating, and exercise in an attempt to prevent cardiovascular events. In the same way, it might be possible to screen people for biomarker risk factors and prescribe a drug and/or a lifestyle change to prevent RA or even prevent many of the other rheumatic diseases including lupus and Sjögren’s syndrome.
Methotrexate
The Dutch TREAT EARLIER (Treat Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid Arthritis) trial is unique among the RA prevention trials for its inclusion of patients with clinically suspect arthralgia and subclinical inflammation on MRI in the hand or foot without any requirement for seropositivity. The trial’s 200 participants are randomized to methotrexate or placebo for 1 year. All subjects receive an initial 120-mg intramuscular injection of methylprednisolone. The primary outcome measured at 2 years is the frequency of clinically detectable arthritis fulfilling the 2010 European League Against Rheumatism/American College of Rheumatology criteria for RA or of unclassified arthritis with a swollen joint count of more than two joints, both persisting for at least 4 weeks. The trial, which is investigator initiated without industry sponsorship, has been enrolling patients for about 1.5 years and will need about that much more time to complete it.
“We do this because we don’t want to confine ourselves to autoantibody-positive patients; we also want to include the autoantibody-negative patients at risk for RA. That’s relevant because in the past, autoantibody-positive patients had more severe disease and more severe joint destruction, but clinically relevant joint destruction doesn’t develop anymore [because of effective treatment], and the problem is more that RA is still a chronic disease. Both ACPA-positive and -negative RA are chronic diseases.”
All the patients included in the trial are considered to be at risk for RA by rheumatologists because of their arthralgia. Because of the clinically relevant population, the results of TREAT EARLIER might be generalized more easily to daily practice, she said in an interview.
Abatacept
The APIPPRA (Arthritis Prevention in the Preclinical Phase of Rheumatoid Arthritis with Abatacept) trial hopes to find out whether RA or clinical synovitis can be prevented with abatacept (Orencia) 125 mg weekly by comparing it against placebo over a 12-month period in 206 British and Dutch patients with arthralgia who are rheumatoid factor (RF) and ACPA-positive. Subjects who are RF negative, but who carry high levels of serum ACPA defined as three times the upper limit of normal may be included. There will be a 1-year follow-up after the intervention period to monitor patients for arthritis.
The ARIAA (Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia) trial is randomizing 98 German patients with ACPA-positive arthralgia to 6 months of abatacept 125 mg weekly for 6 months vs. placebo, followed by a 12-month follow-up period. The primary outcome of the double-blind trial is the proportion of patients with an improvement of acute inflammation characterized as improvement of synovitis or osteitis in the MRI of the dominant hand after 6 months of treatment. The proportion of patients who develop RA based on ACR/EULAR 2010 criteria at 6-month intervals is one of a multitude of secondary outcomes that will be measured. Individuals in the study must test positive for ACPA (with or without RF); have joint pain in the hand, feet, knee, shoulder, or elbow for at least 6 weeks prior to inclusion or in past history; and synovitis or osteitis present on MRI of the dominant hand at baseline.
The two abatacept trials, both of which are expected to be completed in 2018, are sponsored by abatacept’s manufacturer, Bristol-Myers Squibb.
Rituximab
Results from the randomized, placebo-controlled PRAIRI (Prevention of RA by Rituximab) trial that were reported at the annual European Congress of Rheumatology in June showed that a single, intravenous infusion of 1,000 mg of rituximab (Rituxan) given to people with arthralgia and a high risk for developing rheumatoid arthritis did not prevent RA, but the treatment did appear to delay the development of RA. During follow-up, 16 of the 40 people in the placebo group (40%) developed RA after a median of 12 months, and 14 of the 41 in the treated arm (34%) developed RA after a median of 17 months. A Kaplan-Meier survival analysis found that the development of RA in 25% of people occurred at about 12 months in the placebo arm, whereas in the intervention arm it did not occur until 24 months.
At three Dutch centers, the PRAIRI trial investigators enrolled people with arthralgia who had never been diagnosed with arthritis, had never used a disease-modifying antirheumatic drug, and had at least one of these two risk factors: a serum level of IgM rheumatoid factor of more than 12.5 IU/mL and a serum level of anticitrullinated peptide antibodies of more than 25 IU/mL. Enrolled participants also needed to have at least one of the following: a serum level of C-reactive protein greater than 3 mg/L, an erythrocyte sedimentation rate of greater than 28 mm/hr, and evidence of subclinical synovitis identified by either ultrasound or MRI.
Atorvastatin
The STAPRA (Statins to Prevent Rheumatoid Arthritis) trial is randomizing 220 people to double-blind treatment with either atorvastatin 40 mg or placebo for 3 years to determine whether the combined lipid-lowering and anti-inflammatory effects of statin therapy may be able to prevent the development of clinical arthritis in people at increased risk for RA. The participants must test positive for RF and ACPA or a high ACPA titer of three times the cut-off value. Arthralgia is not required, and participants must not have current clinically apparent synovitis. The main endpoint is the development of clinical arthritis as confirmed by a rheumatologist in the study. The trial is scheduled to be completed in 2020.
Investigators across the United States and Europe hope to answer questions surrounding the feasibility of preventing rheumatoid arthritis in a series of proof-of-concept clinical trials that are enrolling patients with various risk factors for the disease. At least five trials have begun – with one already completed – to prevent RA with disease-modifying antirheumatic drugs, including a U.S. trial with hydroxychloroquine and European trials involving methotrexate, rituximab, and abatacept. Another trial with atorvastatin is also underway.
All of the trials involve participants with different risk factors for RA and may thereby provide a range of answers about where the most promising areas for disease prevention lie.
Hydroxychloroquine
Perhaps the broadest in scope of all the studies investigating the prevention of RA is the StopRA (Strategy to Prevent the Onset of Clinically Apparent Rheumatoid Arthritis) trial, which is randomizing 200 subjects with an anticyclic citrullinated peptide 3 (anti-CCP3) that’s greater than twice the normal level, with or without arthralgia, to either hydroxychloroquine (HCQ) 200-400 mg/day or placebo for 1 year, followed by 2 years of follow-up. Pilot data indicated that a level of 40 U/mL or higher of anti-CCP3, which is twice the normal level for positivity, gave a 50% chance of developing RA in the next 3 years regardless of symptoms, family history, or other factors.
The trial’s focus on people with an elevated level of anti-CCP3 limits it to just seropositive individuals, specifically those who are anti-citrullinated protein antibody (ACPA)-positive who constitute about 60%-70% of RA patients with established RA.
The investigators chose to use HCQ because it is a safe and well-tolerated medication for RA, and it may have mechanisms of action that may work particularly well in the early development of RA by blocking inflammation and epitope spreading, Dr. Deane said. “While hydroxychloroquine might not be powerful enough to stop active RA, we hypothesize that it’s just the right drug to block key processes early in its development,” Dr. Deane said in an interview, noting that HCQ is also used to block disease flares in palindromic rheumatism and diminish autoantibody responses in systemic lupus erythematosus.
The StopRA trial is being performed by the Autoimmunity Centers of Excellence, a network sponsored by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. Enrollment began at 18 U.S. sites in April 2016 with screening of first-degree relatives of patients with RA, community-based screening at health fairs, and finding CCP positive individuals without inflammatory arthritis in rheumatology clinics. The investigators estimate that they will need to screen 20,000 individuals to enroll 200 into the study. Dr. Deane said that he and his coinvestigators hope to use the variables that will arise from the diverse population to later determine subgroups who may respond best to the intervention. “We were concerned that if we made everybody too similar we wouldn’t be able to analyze whether symptoms or other factors mattered or not in who responded to the intervention. It may also allow us to catch some people at an early phase of their autoimmunity and others at a later phase and to determine for future studies when is the best time to intervene in preclinical RA with HCQ.”
It’s possible that HCQ will just delay RA rather than prevent it, Dr. Deane said, perhaps indicating that they may find that HCQ needs to be used longer. In any case, by the time the trial is completed in 2020 the investigators hope to gain rich natural history data to determine how to proceed in future trials, whether they use higher doses, longer-term dosing, or try a different target. In addition, the infrastructure of study sites established in StopRA should be incredibly valuable for future prevention studies.
“I envision a future where everybody is screened for RA risk using good blood tests and then given the opportunity for prevention,” first involving high-risk groups such as family members of people with RA, and then ultimately opening up to population-based screening because 90% of RA occurs in individuals without family history of the disease, Dr. Deane said. An analogy for this might be cardiovascular disease, he said, where we screen the cholesterol level of patients before they have had a heart attack, and if it’s above a certain threshold we prescribe a statin, healthy eating, and exercise in an attempt to prevent cardiovascular events. In the same way, it might be possible to screen people for biomarker risk factors and prescribe a drug and/or a lifestyle change to prevent RA or even prevent many of the other rheumatic diseases including lupus and Sjögren’s syndrome.
Methotrexate
The Dutch TREAT EARLIER (Treat Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid Arthritis) trial is unique among the RA prevention trials for its inclusion of patients with clinically suspect arthralgia and subclinical inflammation on MRI in the hand or foot without any requirement for seropositivity. The trial’s 200 participants are randomized to methotrexate or placebo for 1 year. All subjects receive an initial 120-mg intramuscular injection of methylprednisolone. The primary outcome measured at 2 years is the frequency of clinically detectable arthritis fulfilling the 2010 European League Against Rheumatism/American College of Rheumatology criteria for RA or of unclassified arthritis with a swollen joint count of more than two joints, both persisting for at least 4 weeks. The trial, which is investigator initiated without industry sponsorship, has been enrolling patients for about 1.5 years and will need about that much more time to complete it.
“We do this because we don’t want to confine ourselves to autoantibody-positive patients; we also want to include the autoantibody-negative patients at risk for RA. That’s relevant because in the past, autoantibody-positive patients had more severe disease and more severe joint destruction, but clinically relevant joint destruction doesn’t develop anymore [because of effective treatment], and the problem is more that RA is still a chronic disease. Both ACPA-positive and -negative RA are chronic diseases.”
All the patients included in the trial are considered to be at risk for RA by rheumatologists because of their arthralgia. Because of the clinically relevant population, the results of TREAT EARLIER might be generalized more easily to daily practice, she said in an interview.
Abatacept
The APIPPRA (Arthritis Prevention in the Preclinical Phase of Rheumatoid Arthritis with Abatacept) trial hopes to find out whether RA or clinical synovitis can be prevented with abatacept (Orencia) 125 mg weekly by comparing it against placebo over a 12-month period in 206 British and Dutch patients with arthralgia who are rheumatoid factor (RF) and ACPA-positive. Subjects who are RF negative, but who carry high levels of serum ACPA defined as three times the upper limit of normal may be included. There will be a 1-year follow-up after the intervention period to monitor patients for arthritis.
The ARIAA (Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia) trial is randomizing 98 German patients with ACPA-positive arthralgia to 6 months of abatacept 125 mg weekly for 6 months vs. placebo, followed by a 12-month follow-up period. The primary outcome of the double-blind trial is the proportion of patients with an improvement of acute inflammation characterized as improvement of synovitis or osteitis in the MRI of the dominant hand after 6 months of treatment. The proportion of patients who develop RA based on ACR/EULAR 2010 criteria at 6-month intervals is one of a multitude of secondary outcomes that will be measured. Individuals in the study must test positive for ACPA (with or without RF); have joint pain in the hand, feet, knee, shoulder, or elbow for at least 6 weeks prior to inclusion or in past history; and synovitis or osteitis present on MRI of the dominant hand at baseline.
The two abatacept trials, both of which are expected to be completed in 2018, are sponsored by abatacept’s manufacturer, Bristol-Myers Squibb.
Rituximab
Results from the randomized, placebo-controlled PRAIRI (Prevention of RA by Rituximab) trial that were reported at the annual European Congress of Rheumatology in June showed that a single, intravenous infusion of 1,000 mg of rituximab (Rituxan) given to people with arthralgia and a high risk for developing rheumatoid arthritis did not prevent RA, but the treatment did appear to delay the development of RA. During follow-up, 16 of the 40 people in the placebo group (40%) developed RA after a median of 12 months, and 14 of the 41 in the treated arm (34%) developed RA after a median of 17 months. A Kaplan-Meier survival analysis found that the development of RA in 25% of people occurred at about 12 months in the placebo arm, whereas in the intervention arm it did not occur until 24 months.
At three Dutch centers, the PRAIRI trial investigators enrolled people with arthralgia who had never been diagnosed with arthritis, had never used a disease-modifying antirheumatic drug, and had at least one of these two risk factors: a serum level of IgM rheumatoid factor of more than 12.5 IU/mL and a serum level of anticitrullinated peptide antibodies of more than 25 IU/mL. Enrolled participants also needed to have at least one of the following: a serum level of C-reactive protein greater than 3 mg/L, an erythrocyte sedimentation rate of greater than 28 mm/hr, and evidence of subclinical synovitis identified by either ultrasound or MRI.
Atorvastatin
The STAPRA (Statins to Prevent Rheumatoid Arthritis) trial is randomizing 220 people to double-blind treatment with either atorvastatin 40 mg or placebo for 3 years to determine whether the combined lipid-lowering and anti-inflammatory effects of statin therapy may be able to prevent the development of clinical arthritis in people at increased risk for RA. The participants must test positive for RF and ACPA or a high ACPA titer of three times the cut-off value. Arthralgia is not required, and participants must not have current clinically apparent synovitis. The main endpoint is the development of clinical arthritis as confirmed by a rheumatologist in the study. The trial is scheduled to be completed in 2020.
Investigators across the United States and Europe hope to answer questions surrounding the feasibility of preventing rheumatoid arthritis in a series of proof-of-concept clinical trials that are enrolling patients with various risk factors for the disease. At least five trials have begun – with one already completed – to prevent RA with disease-modifying antirheumatic drugs, including a U.S. trial with hydroxychloroquine and European trials involving methotrexate, rituximab, and abatacept. Another trial with atorvastatin is also underway.
All of the trials involve participants with different risk factors for RA and may thereby provide a range of answers about where the most promising areas for disease prevention lie.
Hydroxychloroquine
Perhaps the broadest in scope of all the studies investigating the prevention of RA is the StopRA (Strategy to Prevent the Onset of Clinically Apparent Rheumatoid Arthritis) trial, which is randomizing 200 subjects with an anticyclic citrullinated peptide 3 (anti-CCP3) that’s greater than twice the normal level, with or without arthralgia, to either hydroxychloroquine (HCQ) 200-400 mg/day or placebo for 1 year, followed by 2 years of follow-up. Pilot data indicated that a level of 40 U/mL or higher of anti-CCP3, which is twice the normal level for positivity, gave a 50% chance of developing RA in the next 3 years regardless of symptoms, family history, or other factors.
The trial’s focus on people with an elevated level of anti-CCP3 limits it to just seropositive individuals, specifically those who are anti-citrullinated protein antibody (ACPA)-positive who constitute about 60%-70% of RA patients with established RA.
The investigators chose to use HCQ because it is a safe and well-tolerated medication for RA, and it may have mechanisms of action that may work particularly well in the early development of RA by blocking inflammation and epitope spreading, Dr. Deane said. “While hydroxychloroquine might not be powerful enough to stop active RA, we hypothesize that it’s just the right drug to block key processes early in its development,” Dr. Deane said in an interview, noting that HCQ is also used to block disease flares in palindromic rheumatism and diminish autoantibody responses in systemic lupus erythematosus.
The StopRA trial is being performed by the Autoimmunity Centers of Excellence, a network sponsored by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. Enrollment began at 18 U.S. sites in April 2016 with screening of first-degree relatives of patients with RA, community-based screening at health fairs, and finding CCP positive individuals without inflammatory arthritis in rheumatology clinics. The investigators estimate that they will need to screen 20,000 individuals to enroll 200 into the study. Dr. Deane said that he and his coinvestigators hope to use the variables that will arise from the diverse population to later determine subgroups who may respond best to the intervention. “We were concerned that if we made everybody too similar we wouldn’t be able to analyze whether symptoms or other factors mattered or not in who responded to the intervention. It may also allow us to catch some people at an early phase of their autoimmunity and others at a later phase and to determine for future studies when is the best time to intervene in preclinical RA with HCQ.”
It’s possible that HCQ will just delay RA rather than prevent it, Dr. Deane said, perhaps indicating that they may find that HCQ needs to be used longer. In any case, by the time the trial is completed in 2020 the investigators hope to gain rich natural history data to determine how to proceed in future trials, whether they use higher doses, longer-term dosing, or try a different target. In addition, the infrastructure of study sites established in StopRA should be incredibly valuable for future prevention studies.
“I envision a future where everybody is screened for RA risk using good blood tests and then given the opportunity for prevention,” first involving high-risk groups such as family members of people with RA, and then ultimately opening up to population-based screening because 90% of RA occurs in individuals without family history of the disease, Dr. Deane said. An analogy for this might be cardiovascular disease, he said, where we screen the cholesterol level of patients before they have had a heart attack, and if it’s above a certain threshold we prescribe a statin, healthy eating, and exercise in an attempt to prevent cardiovascular events. In the same way, it might be possible to screen people for biomarker risk factors and prescribe a drug and/or a lifestyle change to prevent RA or even prevent many of the other rheumatic diseases including lupus and Sjögren’s syndrome.
Methotrexate
The Dutch TREAT EARLIER (Treat Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid Arthritis) trial is unique among the RA prevention trials for its inclusion of patients with clinically suspect arthralgia and subclinical inflammation on MRI in the hand or foot without any requirement for seropositivity. The trial’s 200 participants are randomized to methotrexate or placebo for 1 year. All subjects receive an initial 120-mg intramuscular injection of methylprednisolone. The primary outcome measured at 2 years is the frequency of clinically detectable arthritis fulfilling the 2010 European League Against Rheumatism/American College of Rheumatology criteria for RA or of unclassified arthritis with a swollen joint count of more than two joints, both persisting for at least 4 weeks. The trial, which is investigator initiated without industry sponsorship, has been enrolling patients for about 1.5 years and will need about that much more time to complete it.
“We do this because we don’t want to confine ourselves to autoantibody-positive patients; we also want to include the autoantibody-negative patients at risk for RA. That’s relevant because in the past, autoantibody-positive patients had more severe disease and more severe joint destruction, but clinically relevant joint destruction doesn’t develop anymore [because of effective treatment], and the problem is more that RA is still a chronic disease. Both ACPA-positive and -negative RA are chronic diseases.”
All the patients included in the trial are considered to be at risk for RA by rheumatologists because of their arthralgia. Because of the clinically relevant population, the results of TREAT EARLIER might be generalized more easily to daily practice, she said in an interview.
Abatacept
The APIPPRA (Arthritis Prevention in the Preclinical Phase of Rheumatoid Arthritis with Abatacept) trial hopes to find out whether RA or clinical synovitis can be prevented with abatacept (Orencia) 125 mg weekly by comparing it against placebo over a 12-month period in 206 British and Dutch patients with arthralgia who are rheumatoid factor (RF) and ACPA-positive. Subjects who are RF negative, but who carry high levels of serum ACPA defined as three times the upper limit of normal may be included. There will be a 1-year follow-up after the intervention period to monitor patients for arthritis.
The ARIAA (Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia) trial is randomizing 98 German patients with ACPA-positive arthralgia to 6 months of abatacept 125 mg weekly for 6 months vs. placebo, followed by a 12-month follow-up period. The primary outcome of the double-blind trial is the proportion of patients with an improvement of acute inflammation characterized as improvement of synovitis or osteitis in the MRI of the dominant hand after 6 months of treatment. The proportion of patients who develop RA based on ACR/EULAR 2010 criteria at 6-month intervals is one of a multitude of secondary outcomes that will be measured. Individuals in the study must test positive for ACPA (with or without RF); have joint pain in the hand, feet, knee, shoulder, or elbow for at least 6 weeks prior to inclusion or in past history; and synovitis or osteitis present on MRI of the dominant hand at baseline.
The two abatacept trials, both of which are expected to be completed in 2018, are sponsored by abatacept’s manufacturer, Bristol-Myers Squibb.
Rituximab
Results from the randomized, placebo-controlled PRAIRI (Prevention of RA by Rituximab) trial that were reported at the annual European Congress of Rheumatology in June showed that a single, intravenous infusion of 1,000 mg of rituximab (Rituxan) given to people with arthralgia and a high risk for developing rheumatoid arthritis did not prevent RA, but the treatment did appear to delay the development of RA. During follow-up, 16 of the 40 people in the placebo group (40%) developed RA after a median of 12 months, and 14 of the 41 in the treated arm (34%) developed RA after a median of 17 months. A Kaplan-Meier survival analysis found that the development of RA in 25% of people occurred at about 12 months in the placebo arm, whereas in the intervention arm it did not occur until 24 months.
At three Dutch centers, the PRAIRI trial investigators enrolled people with arthralgia who had never been diagnosed with arthritis, had never used a disease-modifying antirheumatic drug, and had at least one of these two risk factors: a serum level of IgM rheumatoid factor of more than 12.5 IU/mL and a serum level of anticitrullinated peptide antibodies of more than 25 IU/mL. Enrolled participants also needed to have at least one of the following: a serum level of C-reactive protein greater than 3 mg/L, an erythrocyte sedimentation rate of greater than 28 mm/hr, and evidence of subclinical synovitis identified by either ultrasound or MRI.
Atorvastatin
The STAPRA (Statins to Prevent Rheumatoid Arthritis) trial is randomizing 220 people to double-blind treatment with either atorvastatin 40 mg or placebo for 3 years to determine whether the combined lipid-lowering and anti-inflammatory effects of statin therapy may be able to prevent the development of clinical arthritis in people at increased risk for RA. The participants must test positive for RF and ACPA or a high ACPA titer of three times the cut-off value. Arthralgia is not required, and participants must not have current clinically apparent synovitis. The main endpoint is the development of clinical arthritis as confirmed by a rheumatologist in the study. The trial is scheduled to be completed in 2020.
Pain starting in knee later arises in other joints
People who develop knee pain associated with osteoarthritis often subsequently develop pain in other joints, according to a study of two observational, community-based cohorts that could not discern any pattern of new pain sites.
In the “first investigation of the association of knee pain with pain in multiple other sites,” David T. Felson, MD, of Boston University and his colleagues reported that the regions where pain developed after first appearing in the knee varied from person to person and occurred in both upper and lower extremities, which goes against the hypothesis that adjacent joints are most often affected by knee pain.
The study involved patients from the MOST (Multicenter Osteoarthritis Study) trial, including 281 with knee pain at the index visit (168 unilaterally) and 852 without, as well as patients from OAI (the Osteoarthritis Initiative), including 412 with knee pain at the index visit (241 unilaterally), and 1,941 without. The investigators assessed the patients’ data for 14 total joints outside of the knees: 2 each of feet, ankles, hips, hands, wrists, elbows, and shoulders (Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39848).
Patients with new-onset knee pain at the index visit reported a mean of 2.3 painful joints outside the knee, compared with a significantly lower number of 1.3 reported by those without knee pain. The mean number of nonknee joints with pain was higher among patients with bilateral knee pain, compared with unilateral knee pain. The percentage of patients who reported pain outside the knee rose with the number of painful knees: 80% for two, 64% for one, and 50% for none.
The patients who developed new unilateral knee pain at the index visit also experienced an increase in prevalent joint pain in multiple joints in upper- and lower-extremity sites. In particular, the investigators noted that ipsilateral prevalent hip joint pain, which they characterized as pain in the groin or front of the thigh, was more than twice as likely to occur among those with new unilateral knee pain at the index visit, but the odds for contralateral hip joint pain did not reach statistical significance. The comparisons were adjusted for age, sex, body mass index, depression at the index visit, study (MOST or OAI), and count of painful upper and lower limb joints at the index visit (excluding knees).
When examining only patients with new-onset joint pain outside of the knee, the odds of patients with new knee pain to later develop new-onset joint pain outside the knee were 30% higher than for those without knee pain. Patients with new knee pain had a mean 2.6 new painful joints out of 12.1 eligible joints, compared with 2.0 new painful joints in those without knee pain out of 12.7 eligible joints. (Joint regions with prevalent symptoms at the index visit were excluded as incident painful sites.) Patients with knee pain also had a consistently higher rate of new-onset pain in nonknee joints when compared with patients without knee pain in at least half of the follow-up visits over the course of the MOST and OAI studies. Sensitivity analyses indicated that the association between knee pain and subsequent pain in other joints was not driven by the inclusion of patients with widespread pain.
“There was no clear-cut predilection for pain in any specific lower-extremity joint region,” the investigators wrote.
The investigators noted that other researchers have suggested that patients with knee pain may be at higher risk for lower-extremity joint pain because of changes to their gait that gradually cause damage to other joints, but evidence in this study doesn’t “necessarily support the argument that in persons with knee pain, aberrant loading by altered movement patterns induces pain in only nearby joints. Our findings suggest that the sites affected are more than just hip and ankle and that there is no special predilection for pain in these locations.”
While the investigators cannot differentiate underlying mechanisms for their study’s finding of multiple co-occurring sites of joint pain in people with new-onset knee pain, they suggested that it “supports either a predilection for osteoarthritic changes at multiple joint sites and/or raises the possibility that nervous system–driven pain sensitization increases the risk not only of widespread pain but even of regional pain. Since symptomatic OA is unusual in some of these painful sites (e.g., elbow, shoulder, ankle), pain sensitization would seem a more likely explanation.”
Some of the study’s limitations described by the investigators included the uncertainty surrounding whether new-onset knee pain was truly new onset or whether it was a reoccurrence, and also the fact that most of the people in the two cohorts had multiple sites of joint pain at both the baseline and the index visit and there were too few people with no sites of pain outside the knee to carry out subanalyses in that group, which “speaks to the high prevalence of multiple joint pains in older adult cohorts.”
The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.
People who develop knee pain associated with osteoarthritis often subsequently develop pain in other joints, according to a study of two observational, community-based cohorts that could not discern any pattern of new pain sites.
In the “first investigation of the association of knee pain with pain in multiple other sites,” David T. Felson, MD, of Boston University and his colleagues reported that the regions where pain developed after first appearing in the knee varied from person to person and occurred in both upper and lower extremities, which goes against the hypothesis that adjacent joints are most often affected by knee pain.
The study involved patients from the MOST (Multicenter Osteoarthritis Study) trial, including 281 with knee pain at the index visit (168 unilaterally) and 852 without, as well as patients from OAI (the Osteoarthritis Initiative), including 412 with knee pain at the index visit (241 unilaterally), and 1,941 without. The investigators assessed the patients’ data for 14 total joints outside of the knees: 2 each of feet, ankles, hips, hands, wrists, elbows, and shoulders (Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39848).
Patients with new-onset knee pain at the index visit reported a mean of 2.3 painful joints outside the knee, compared with a significantly lower number of 1.3 reported by those without knee pain. The mean number of nonknee joints with pain was higher among patients with bilateral knee pain, compared with unilateral knee pain. The percentage of patients who reported pain outside the knee rose with the number of painful knees: 80% for two, 64% for one, and 50% for none.
The patients who developed new unilateral knee pain at the index visit also experienced an increase in prevalent joint pain in multiple joints in upper- and lower-extremity sites. In particular, the investigators noted that ipsilateral prevalent hip joint pain, which they characterized as pain in the groin or front of the thigh, was more than twice as likely to occur among those with new unilateral knee pain at the index visit, but the odds for contralateral hip joint pain did not reach statistical significance. The comparisons were adjusted for age, sex, body mass index, depression at the index visit, study (MOST or OAI), and count of painful upper and lower limb joints at the index visit (excluding knees).
When examining only patients with new-onset joint pain outside of the knee, the odds of patients with new knee pain to later develop new-onset joint pain outside the knee were 30% higher than for those without knee pain. Patients with new knee pain had a mean 2.6 new painful joints out of 12.1 eligible joints, compared with 2.0 new painful joints in those without knee pain out of 12.7 eligible joints. (Joint regions with prevalent symptoms at the index visit were excluded as incident painful sites.) Patients with knee pain also had a consistently higher rate of new-onset pain in nonknee joints when compared with patients without knee pain in at least half of the follow-up visits over the course of the MOST and OAI studies. Sensitivity analyses indicated that the association between knee pain and subsequent pain in other joints was not driven by the inclusion of patients with widespread pain.
“There was no clear-cut predilection for pain in any specific lower-extremity joint region,” the investigators wrote.
The investigators noted that other researchers have suggested that patients with knee pain may be at higher risk for lower-extremity joint pain because of changes to their gait that gradually cause damage to other joints, but evidence in this study doesn’t “necessarily support the argument that in persons with knee pain, aberrant loading by altered movement patterns induces pain in only nearby joints. Our findings suggest that the sites affected are more than just hip and ankle and that there is no special predilection for pain in these locations.”
While the investigators cannot differentiate underlying mechanisms for their study’s finding of multiple co-occurring sites of joint pain in people with new-onset knee pain, they suggested that it “supports either a predilection for osteoarthritic changes at multiple joint sites and/or raises the possibility that nervous system–driven pain sensitization increases the risk not only of widespread pain but even of regional pain. Since symptomatic OA is unusual in some of these painful sites (e.g., elbow, shoulder, ankle), pain sensitization would seem a more likely explanation.”
Some of the study’s limitations described by the investigators included the uncertainty surrounding whether new-onset knee pain was truly new onset or whether it was a reoccurrence, and also the fact that most of the people in the two cohorts had multiple sites of joint pain at both the baseline and the index visit and there were too few people with no sites of pain outside the knee to carry out subanalyses in that group, which “speaks to the high prevalence of multiple joint pains in older adult cohorts.”
The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.
People who develop knee pain associated with osteoarthritis often subsequently develop pain in other joints, according to a study of two observational, community-based cohorts that could not discern any pattern of new pain sites.
In the “first investigation of the association of knee pain with pain in multiple other sites,” David T. Felson, MD, of Boston University and his colleagues reported that the regions where pain developed after first appearing in the knee varied from person to person and occurred in both upper and lower extremities, which goes against the hypothesis that adjacent joints are most often affected by knee pain.
The study involved patients from the MOST (Multicenter Osteoarthritis Study) trial, including 281 with knee pain at the index visit (168 unilaterally) and 852 without, as well as patients from OAI (the Osteoarthritis Initiative), including 412 with knee pain at the index visit (241 unilaterally), and 1,941 without. The investigators assessed the patients’ data for 14 total joints outside of the knees: 2 each of feet, ankles, hips, hands, wrists, elbows, and shoulders (Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39848).
Patients with new-onset knee pain at the index visit reported a mean of 2.3 painful joints outside the knee, compared with a significantly lower number of 1.3 reported by those without knee pain. The mean number of nonknee joints with pain was higher among patients with bilateral knee pain, compared with unilateral knee pain. The percentage of patients who reported pain outside the knee rose with the number of painful knees: 80% for two, 64% for one, and 50% for none.
The patients who developed new unilateral knee pain at the index visit also experienced an increase in prevalent joint pain in multiple joints in upper- and lower-extremity sites. In particular, the investigators noted that ipsilateral prevalent hip joint pain, which they characterized as pain in the groin or front of the thigh, was more than twice as likely to occur among those with new unilateral knee pain at the index visit, but the odds for contralateral hip joint pain did not reach statistical significance. The comparisons were adjusted for age, sex, body mass index, depression at the index visit, study (MOST or OAI), and count of painful upper and lower limb joints at the index visit (excluding knees).
When examining only patients with new-onset joint pain outside of the knee, the odds of patients with new knee pain to later develop new-onset joint pain outside the knee were 30% higher than for those without knee pain. Patients with new knee pain had a mean 2.6 new painful joints out of 12.1 eligible joints, compared with 2.0 new painful joints in those without knee pain out of 12.7 eligible joints. (Joint regions with prevalent symptoms at the index visit were excluded as incident painful sites.) Patients with knee pain also had a consistently higher rate of new-onset pain in nonknee joints when compared with patients without knee pain in at least half of the follow-up visits over the course of the MOST and OAI studies. Sensitivity analyses indicated that the association between knee pain and subsequent pain in other joints was not driven by the inclusion of patients with widespread pain.
“There was no clear-cut predilection for pain in any specific lower-extremity joint region,” the investigators wrote.
The investigators noted that other researchers have suggested that patients with knee pain may be at higher risk for lower-extremity joint pain because of changes to their gait that gradually cause damage to other joints, but evidence in this study doesn’t “necessarily support the argument that in persons with knee pain, aberrant loading by altered movement patterns induces pain in only nearby joints. Our findings suggest that the sites affected are more than just hip and ankle and that there is no special predilection for pain in these locations.”
While the investigators cannot differentiate underlying mechanisms for their study’s finding of multiple co-occurring sites of joint pain in people with new-onset knee pain, they suggested that it “supports either a predilection for osteoarthritic changes at multiple joint sites and/or raises the possibility that nervous system–driven pain sensitization increases the risk not only of widespread pain but even of regional pain. Since symptomatic OA is unusual in some of these painful sites (e.g., elbow, shoulder, ankle), pain sensitization would seem a more likely explanation.”
Some of the study’s limitations described by the investigators included the uncertainty surrounding whether new-onset knee pain was truly new onset or whether it was a reoccurrence, and also the fact that most of the people in the two cohorts had multiple sites of joint pain at both the baseline and the index visit and there were too few people with no sites of pain outside the knee to carry out subanalyses in that group, which “speaks to the high prevalence of multiple joint pains in older adult cohorts.”
The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:People with frequently painful knees often develop pain in joints outside the knee, and the sites vary from person to person.
Major finding: The odds of patients with new knee pain to later develop joint pain outside the knee were 30% higher than for those without knee pain.
Data source: A study of 693 persons with index visit knee pain and 2,793 without it from two community-based cohorts.
Disclosures: The research was supported by grants from the National Institutes of Health. The authors had no disclosures to report.
Biosimilar version of etanercept gains FDA approval
A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.
Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.
The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.
“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.
Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.
A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.
Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.
The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.
“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.
Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.
A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.
Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.
The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.
“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.
Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.
Calcineurin inhibitor proves effective against lupus nephritis
Patients with highly active lupus nephritis who took the investigational oral calcineurin inhibitor voclosporin plus mycophenolate mofetil and tapered corticosteroids were twice as likely to achieve complete remission by 24 weeks, compared against placebo-treated patients who also received standard of care treatment in a phase IIb study trial reported by Aurinia Pharmaceuticals.
The 24-week complete remission primary endpoint of the AURA-LV(Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study – defined as a urine protein/creatinine ratio of 0.5 mg/mg or less as well as normal stable renal function (estimated glomerular filtration rate of 60 mL/min per 1.73 m2 or greater or no confirmed decrease from baseline in eGFR of 20% or greater) – occurred in 32.6% of patients who were randomized to take 23.7 mg of voclosporin twice daily, which was significantly higher than the 19.3% rate observed in the placebo-treated group. The rate was 27.3% in a higher-dose group that received 39.5 mg of voclosporin twice daily.
Serious adverse events occurred at higher rates in both voclosporin arms of the trial than in the placebo arm, but Aurinia said in its statement announcing the results that the nature of the events was consistent with highly active lupus nephritis. A total of 13 deaths occurred, including 2 in the high-dose arm, 10 in the low-dose arm, and 1 in the placebo arm, but the company said that the investigator deemed the deaths as unrelated to voclosporin. Eleven of the deaths occurred in Asia.
Both low- and high-dose voclosporin arms attained a partial response by 24 weeks (50% drop in urine protein per creatinine ratio) in a significantly higher percentage of patients than did the placebo arm (69.7% and 65.9%, respectively, vs. 49.4%).
The Lupus Research Alliance welcomed the results of the study but noted that more needs to be known about the risk-benefit profile of the drug, specifically in reference to the 12 deaths reported in those who took voclosporin. “The magnitude of benefit is quite striking and unprecedented in lupus nephritis, but the number of deaths is a concern that must be taken seriously. We are very hopeful that further analysis of the safety data will confirm that voclosporin can provide a safe and effective treatment,” Margaret G. Dowd, co–chief executive officer of the Lupus Research Alliance, said in a statement.
The trial enrolled and randomized 265 patients diagnosed with highly active lupus nephritis (according to clinical signs and renal biopsy features) across centers in more than 20 countries. Besides being randomized to either active treatment arm or placebo, all patients received mycophenolate mofetil (CellCept) and oral corticosteroids that started at 20-25 mg/daily and then tapered down to 5 mg daily by week 8 and 2.5 mg daily by week 16. All patients also had an initial 500-1,000 mg intravenous dose of steroids.
Aurinia said that the study will continue to 48 weeks, and these data will be available in early 2017.
Patients with highly active lupus nephritis who took the investigational oral calcineurin inhibitor voclosporin plus mycophenolate mofetil and tapered corticosteroids were twice as likely to achieve complete remission by 24 weeks, compared against placebo-treated patients who also received standard of care treatment in a phase IIb study trial reported by Aurinia Pharmaceuticals.
The 24-week complete remission primary endpoint of the AURA-LV(Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study – defined as a urine protein/creatinine ratio of 0.5 mg/mg or less as well as normal stable renal function (estimated glomerular filtration rate of 60 mL/min per 1.73 m2 or greater or no confirmed decrease from baseline in eGFR of 20% or greater) – occurred in 32.6% of patients who were randomized to take 23.7 mg of voclosporin twice daily, which was significantly higher than the 19.3% rate observed in the placebo-treated group. The rate was 27.3% in a higher-dose group that received 39.5 mg of voclosporin twice daily.
Serious adverse events occurred at higher rates in both voclosporin arms of the trial than in the placebo arm, but Aurinia said in its statement announcing the results that the nature of the events was consistent with highly active lupus nephritis. A total of 13 deaths occurred, including 2 in the high-dose arm, 10 in the low-dose arm, and 1 in the placebo arm, but the company said that the investigator deemed the deaths as unrelated to voclosporin. Eleven of the deaths occurred in Asia.
Both low- and high-dose voclosporin arms attained a partial response by 24 weeks (50% drop in urine protein per creatinine ratio) in a significantly higher percentage of patients than did the placebo arm (69.7% and 65.9%, respectively, vs. 49.4%).
The Lupus Research Alliance welcomed the results of the study but noted that more needs to be known about the risk-benefit profile of the drug, specifically in reference to the 12 deaths reported in those who took voclosporin. “The magnitude of benefit is quite striking and unprecedented in lupus nephritis, but the number of deaths is a concern that must be taken seriously. We are very hopeful that further analysis of the safety data will confirm that voclosporin can provide a safe and effective treatment,” Margaret G. Dowd, co–chief executive officer of the Lupus Research Alliance, said in a statement.
The trial enrolled and randomized 265 patients diagnosed with highly active lupus nephritis (according to clinical signs and renal biopsy features) across centers in more than 20 countries. Besides being randomized to either active treatment arm or placebo, all patients received mycophenolate mofetil (CellCept) and oral corticosteroids that started at 20-25 mg/daily and then tapered down to 5 mg daily by week 8 and 2.5 mg daily by week 16. All patients also had an initial 500-1,000 mg intravenous dose of steroids.
Aurinia said that the study will continue to 48 weeks, and these data will be available in early 2017.
Patients with highly active lupus nephritis who took the investigational oral calcineurin inhibitor voclosporin plus mycophenolate mofetil and tapered corticosteroids were twice as likely to achieve complete remission by 24 weeks, compared against placebo-treated patients who also received standard of care treatment in a phase IIb study trial reported by Aurinia Pharmaceuticals.
The 24-week complete remission primary endpoint of the AURA-LV(Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study – defined as a urine protein/creatinine ratio of 0.5 mg/mg or less as well as normal stable renal function (estimated glomerular filtration rate of 60 mL/min per 1.73 m2 or greater or no confirmed decrease from baseline in eGFR of 20% or greater) – occurred in 32.6% of patients who were randomized to take 23.7 mg of voclosporin twice daily, which was significantly higher than the 19.3% rate observed in the placebo-treated group. The rate was 27.3% in a higher-dose group that received 39.5 mg of voclosporin twice daily.
Serious adverse events occurred at higher rates in both voclosporin arms of the trial than in the placebo arm, but Aurinia said in its statement announcing the results that the nature of the events was consistent with highly active lupus nephritis. A total of 13 deaths occurred, including 2 in the high-dose arm, 10 in the low-dose arm, and 1 in the placebo arm, but the company said that the investigator deemed the deaths as unrelated to voclosporin. Eleven of the deaths occurred in Asia.
Both low- and high-dose voclosporin arms attained a partial response by 24 weeks (50% drop in urine protein per creatinine ratio) in a significantly higher percentage of patients than did the placebo arm (69.7% and 65.9%, respectively, vs. 49.4%).
The Lupus Research Alliance welcomed the results of the study but noted that more needs to be known about the risk-benefit profile of the drug, specifically in reference to the 12 deaths reported in those who took voclosporin. “The magnitude of benefit is quite striking and unprecedented in lupus nephritis, but the number of deaths is a concern that must be taken seriously. We are very hopeful that further analysis of the safety data will confirm that voclosporin can provide a safe and effective treatment,” Margaret G. Dowd, co–chief executive officer of the Lupus Research Alliance, said in a statement.
The trial enrolled and randomized 265 patients diagnosed with highly active lupus nephritis (according to clinical signs and renal biopsy features) across centers in more than 20 countries. Besides being randomized to either active treatment arm or placebo, all patients received mycophenolate mofetil (CellCept) and oral corticosteroids that started at 20-25 mg/daily and then tapered down to 5 mg daily by week 8 and 2.5 mg daily by week 16. All patients also had an initial 500-1,000 mg intravenous dose of steroids.
Aurinia said that the study will continue to 48 weeks, and these data will be available in early 2017.
RA patients report worse symptoms at diagnosis, despite earlier presentation
Patients with rheumatoid arthritis have steadily made their initial clinical presentation with shorter and shorter symptom durations and less severe inflammation from the early 1990s into the 2010s, but this paradoxically has coincided with gradual increases in the severity of patient-reported outcome measures, according to findings from the Leiden Early Arthritis Cohort.
For 1,406 patients who met 2010 European League Against Rheumatism/American College of Rheumatology rheumatoid arthritis (RA) criteria during 1993-2015, investigators led by Wouter P. Nieuwenhuis, MD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center found that the symptom duration at initial presentation declined significantly from a median 138 days during 1993-1996 to 97 days during 2011-2015. Although the frequency of autoantibodies at presentation did not change significantly, the median number of swollen joints decreased from 12 to 6, median tender joints declined from 21 to 10, and median C-reactive protein levels dropped from 24 mg/L to 10 mg/L (all P values less than .001). All these measures declined steadily during the five time periods analyzed (1993-1996, 1997-2000, 2001-2005, 2006-2010, 2011-2015). Median scores on the Health Assessment Questionnaire, which measures functional disability, stayed the same in all five time periods.
In contrast, patient-reported outcomes measures (PROMs) on visual analog scales for pain, fatigue, and disease activity all rose significantly from 1993-1996 to 2011-2015.
“Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (i.e., society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling. In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes,” the researchers wrote.
They added that the current findings, in light of previous studies that found that PROMs are not responsive to changes in the severity of inflammation, “raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (e.g., Disease Activity Score or Simple Disease Activity Index) for defining remission.”
Read the full study in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209949).
Patients with rheumatoid arthritis have steadily made their initial clinical presentation with shorter and shorter symptom durations and less severe inflammation from the early 1990s into the 2010s, but this paradoxically has coincided with gradual increases in the severity of patient-reported outcome measures, according to findings from the Leiden Early Arthritis Cohort.
For 1,406 patients who met 2010 European League Against Rheumatism/American College of Rheumatology rheumatoid arthritis (RA) criteria during 1993-2015, investigators led by Wouter P. Nieuwenhuis, MD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center found that the symptom duration at initial presentation declined significantly from a median 138 days during 1993-1996 to 97 days during 2011-2015. Although the frequency of autoantibodies at presentation did not change significantly, the median number of swollen joints decreased from 12 to 6, median tender joints declined from 21 to 10, and median C-reactive protein levels dropped from 24 mg/L to 10 mg/L (all P values less than .001). All these measures declined steadily during the five time periods analyzed (1993-1996, 1997-2000, 2001-2005, 2006-2010, 2011-2015). Median scores on the Health Assessment Questionnaire, which measures functional disability, stayed the same in all five time periods.
In contrast, patient-reported outcomes measures (PROMs) on visual analog scales for pain, fatigue, and disease activity all rose significantly from 1993-1996 to 2011-2015.
“Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (i.e., society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling. In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes,” the researchers wrote.
They added that the current findings, in light of previous studies that found that PROMs are not responsive to changes in the severity of inflammation, “raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (e.g., Disease Activity Score or Simple Disease Activity Index) for defining remission.”
Read the full study in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209949).
Patients with rheumatoid arthritis have steadily made their initial clinical presentation with shorter and shorter symptom durations and less severe inflammation from the early 1990s into the 2010s, but this paradoxically has coincided with gradual increases in the severity of patient-reported outcome measures, according to findings from the Leiden Early Arthritis Cohort.
For 1,406 patients who met 2010 European League Against Rheumatism/American College of Rheumatology rheumatoid arthritis (RA) criteria during 1993-2015, investigators led by Wouter P. Nieuwenhuis, MD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center found that the symptom duration at initial presentation declined significantly from a median 138 days during 1993-1996 to 97 days during 2011-2015. Although the frequency of autoantibodies at presentation did not change significantly, the median number of swollen joints decreased from 12 to 6, median tender joints declined from 21 to 10, and median C-reactive protein levels dropped from 24 mg/L to 10 mg/L (all P values less than .001). All these measures declined steadily during the five time periods analyzed (1993-1996, 1997-2000, 2001-2005, 2006-2010, 2011-2015). Median scores on the Health Assessment Questionnaire, which measures functional disability, stayed the same in all five time periods.
In contrast, patient-reported outcomes measures (PROMs) on visual analog scales for pain, fatigue, and disease activity all rose significantly from 1993-1996 to 2011-2015.
“Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (i.e., society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling. In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes,” the researchers wrote.
They added that the current findings, in light of previous studies that found that PROMs are not responsive to changes in the severity of inflammation, “raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (e.g., Disease Activity Score or Simple Disease Activity Index) for defining remission.”
Read the full study in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209949).
FROM ANNALS OF THE RHEUMATIC DISEASES
