Rheumatoid Arthritis

Infliximab is associated with high rates of dose escalation and a larger overall cost, compared with adalimumab and etanercept in patients with rheumatoid arthritis, without any additional gains in effectiveness, according to analysis of data from 563 patients in the Veterans Affairs Rheumatoid Arthritis registry.

Of patients on etanercept, 2% underwent dose escalation, compared with 16% of patients on adalimumab and 64% of patients on infliximab. Annual costs for the first course of TNF inhibitor therapy were $13,100 for adalimumab, $13,500 for etanercept, and $16,900 for the intravenously-administered infliximab.

©Mathier/thinkstockphotos.com

Researchers found the duration of treatment, and persistence with the first course of agent, were similar between treatment groups, and they also saw no statistically significant differences in improvements in mean DAS28 score between the three agents.

"These data and our observations suggest that dose escalation is often associated with added costs without increased benefit," wrote Dr. Grant W. Cannon of the VA Salt Lake City Health Care System and his associates in the Aug. 15 online issue of The Journal of Rheumatology [doi:10.3899/jrheum.140164].

The study was sponsored by Immunex, makers of Enbrel (etanercept); Wyeth, partner of Immunex; and the Veterans Administration Health Services. No other conflicts of interest were declared.

Infliximab is associated with high rates of dose escalation and a larger overall cost, compared with adalimumab and etanercept in patients with rheumatoid arthritis, without any additional gains in effectiveness, according to analysis of data from 563 patients in the Veterans Affairs Rheumatoid Arthritis registry.

Of patients on etanercept, 2% underwent dose escalation, compared with 16% of patients on adalimumab and 64% of patients on infliximab. Annual costs for the first course of TNF inhibitor therapy were $13,100 for adalimumab, $13,500 for etanercept, and $16,900 for the intravenously-administered infliximab.

©Mathier/thinkstockphotos.com

Researchers found the duration of treatment, and persistence with the first course of agent, were similar between treatment groups, and they also saw no statistically significant differences in improvements in mean DAS28 score between the three agents.

"These data and our observations suggest that dose escalation is often associated with added costs without increased benefit," wrote Dr. Grant W. Cannon of the VA Salt Lake City Health Care System and his associates in the Aug. 15 online issue of The Journal of Rheumatology [doi:10.3899/jrheum.140164].

The study was sponsored by Immunex, makers of Enbrel (etanercept); Wyeth, partner of Immunex; and the Veterans Administration Health Services. No other conflicts of interest were declared.

Infliximab is associated with high rates of dose escalation and a larger overall cost, compared with adalimumab and etanercept in patients with rheumatoid arthritis, without any additional gains in effectiveness, according to analysis of data from 563 patients in the Veterans Affairs Rheumatoid Arthritis registry.

Of patients on etanercept, 2% underwent dose escalation, compared with 16% of patients on adalimumab and 64% of patients on infliximab. Annual costs for the first course of TNF inhibitor therapy were $13,100 for adalimumab, $13,500 for etanercept, and $16,900 for the intravenously-administered infliximab.

©Mathier/thinkstockphotos.com

Researchers found the duration of treatment, and persistence with the first course of agent, were similar between treatment groups, and they also saw no statistically significant differences in improvements in mean DAS28 score between the three agents.

"These data and our observations suggest that dose escalation is often associated with added costs without increased benefit," wrote Dr. Grant W. Cannon of the VA Salt Lake City Health Care System and his associates in the Aug. 15 online issue of The Journal of Rheumatology [doi:10.3899/jrheum.140164].

The study was sponsored by Immunex, makers of Enbrel (etanercept); Wyeth, partner of Immunex; and the Veterans Administration Health Services. No other conflicts of interest were declared.

Comprehensive disease control in rheumatoid arthritis is associated with meaningful benefits such as short- and long-term improvements in quality of life, pain, fatigue, and work attendance, a meta-analysis has found.

Using pooled data from three randomized controlled trials of adalimumab plus methotrexate in 1,467 patients with early- or late-stage rheumatoid arthritis, researchers found mean improvements of 20 points in pain scores from baseline, 5.8 points in fatigue scores, 10.8 points in physical quality of life scores, and 3.1 points in mental quality of life scores, among patients who achieved comprehensive disease control at 26 weeks – all of which were significantly greater than those of patients who did not achieve CDC.

Compared with patients achieving Disease Activity Score remission alone, "CDC achievement was associated with statistically significant and clinically meaningful differences of 7.0 (4.0-10.0) and 6.9 (3.5-10.4) in SF-36 PCS [Short Form-36 physical component scores] at weeks 26 and 52, respectively," wrote Dr. Paul Emery and his colleagues. Dr. Emery is director of the Leeds (England) Institute of Rheumatic & Musculoskeletal Medicine, and director of the Leeds Musculoskeletal Biomedical Research Unit.

The researchers defined CDC as achievement of a 28-joint Disease Activity Score using C-reactive protein of less than 2.6, a Health Assessment Questionnaire score below 0.5, and change from baseline in modified total Sharp score of 0.5 or less, according to the paper, which was published online Aug. 19 in Annals of the Rheumatic Diseases (doi: 10.1136/annrheumdis-2014-205302).

The study was funded by AbbVie. Three authors are AbbVie employees, and the other authors reported grant support and consultancies for a range of pharmaceutical companies.

Comprehensive disease control in rheumatoid arthritis is associated with meaningful benefits such as short- and long-term improvements in quality of life, pain, fatigue, and work attendance, a meta-analysis has found.

Using pooled data from three randomized controlled trials of adalimumab plus methotrexate in 1,467 patients with early- or late-stage rheumatoid arthritis, researchers found mean improvements of 20 points in pain scores from baseline, 5.8 points in fatigue scores, 10.8 points in physical quality of life scores, and 3.1 points in mental quality of life scores, among patients who achieved comprehensive disease control at 26 weeks – all of which were significantly greater than those of patients who did not achieve CDC.

Compared with patients achieving Disease Activity Score remission alone, "CDC achievement was associated with statistically significant and clinically meaningful differences of 7.0 (4.0-10.0) and 6.9 (3.5-10.4) in SF-36 PCS [Short Form-36 physical component scores] at weeks 26 and 52, respectively," wrote Dr. Paul Emery and his colleagues. Dr. Emery is director of the Leeds (England) Institute of Rheumatic & Musculoskeletal Medicine, and director of the Leeds Musculoskeletal Biomedical Research Unit.

The researchers defined CDC as achievement of a 28-joint Disease Activity Score using C-reactive protein of less than 2.6, a Health Assessment Questionnaire score below 0.5, and change from baseline in modified total Sharp score of 0.5 or less, according to the paper, which was published online Aug. 19 in Annals of the Rheumatic Diseases (doi: 10.1136/annrheumdis-2014-205302).

The study was funded by AbbVie. Three authors are AbbVie employees, and the other authors reported grant support and consultancies for a range of pharmaceutical companies.

Comprehensive disease control in rheumatoid arthritis is associated with meaningful benefits such as short- and long-term improvements in quality of life, pain, fatigue, and work attendance, a meta-analysis has found.

Using pooled data from three randomized controlled trials of adalimumab plus methotrexate in 1,467 patients with early- or late-stage rheumatoid arthritis, researchers found mean improvements of 20 points in pain scores from baseline, 5.8 points in fatigue scores, 10.8 points in physical quality of life scores, and 3.1 points in mental quality of life scores, among patients who achieved comprehensive disease control at 26 weeks – all of which were significantly greater than those of patients who did not achieve CDC.

Compared with patients achieving Disease Activity Score remission alone, "CDC achievement was associated with statistically significant and clinically meaningful differences of 7.0 (4.0-10.0) and 6.9 (3.5-10.4) in SF-36 PCS [Short Form-36 physical component scores] at weeks 26 and 52, respectively," wrote Dr. Paul Emery and his colleagues. Dr. Emery is director of the Leeds (England) Institute of Rheumatic & Musculoskeletal Medicine, and director of the Leeds Musculoskeletal Biomedical Research Unit.

The researchers defined CDC as achievement of a 28-joint Disease Activity Score using C-reactive protein of less than 2.6, a Health Assessment Questionnaire score below 0.5, and change from baseline in modified total Sharp score of 0.5 or less, according to the paper, which was published online Aug. 19 in Annals of the Rheumatic Diseases (doi: 10.1136/annrheumdis-2014-205302).

The study was funded by AbbVie. Three authors are AbbVie employees, and the other authors reported grant support and consultancies for a range of pharmaceutical companies.

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

jevans@frontlinemedcom.com

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

jevans@frontlinemedcom.com

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

jevans@frontlinemedcom.com

Rheumatoid arthritis increases cardiovascular risks as much as diabetes does, but guidelines and quality indicators fail to adequately address cardiovascular disease prevention for RA patients, authors of the first systematic review on the topic wrote in Arthritis Care & Research.

To date, only one guideline has focused entirely on the topic, and guidelines are too general to be used in adherence or quality improvement efforts, Dr. Claire Barber of the division of rheumatology at the University of Calgary (Alta.) and her associates reported. Furthermore, just four quality indicators have targeted CVD risk in RA patients, the investigators found (Arthritis Care Res. 2014 July 29 [doi:10.1002/acr.22419]).

The researchers searched MEDLINE, EMBASE, CINAHL, Web of Science, and other sources to find 16,064 abstracts on CVD or RA since 2008 that mentioned guidelines or quality indicators. Of these, they fully reviewed 808 manuscripts, and scored 10 guidelines with the six-domain Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument, they said.

Only two guidelines recommended using a cardiovascular risk score, and only one, from the European League Against Rheumatism, suggested adjusting that score to account for RA, the researchers said. The guidelines also lacked thresholds for treating modifiable risk factors and did not clarify whether such thresholds should be lower than for the general population, they added.

Furthermore, the recommendations did clearly guide clinicians on monitoring or treating side effects of drugs such tocilizumab – which can cause dyslipidemia – and leflunomide, which can cause hypertension, said the investigators.

Levels of supporting evidence for guidelines also varied, and many recommendations lacked high-level evidence, particularly related to diet and exercise, the researchers said.

The four quality indicators included general screening for comorbidities, formal estimation of CVD risk, exercise, and minimizing use of steroids, the investigators said. The measures "did not cover the recognized breadth of CVD preventive care in RA," they added.

Future research should focus on how best to evaluate CVD risk in RA patients and should determine thresholds for lipid-lowering medications and other treatments, the investigators said. In the meantime, they recommended developing quality indicators for preventing CVD in RA based on the guidelines reviewed and on general population recommendations.

The research was supported by grants from Alberta Innovates Health Solutions, UCB Canada, the Canadian Rheumatology Association, and the Arthritis Society. The authors did not disclose conflicts of interest.

Rheumatoid arthritis increases cardiovascular risks as much as diabetes does, but guidelines and quality indicators fail to adequately address cardiovascular disease prevention for RA patients, authors of the first systematic review on the topic wrote in Arthritis Care & Research.

To date, only one guideline has focused entirely on the topic, and guidelines are too general to be used in adherence or quality improvement efforts, Dr. Claire Barber of the division of rheumatology at the University of Calgary (Alta.) and her associates reported. Furthermore, just four quality indicators have targeted CVD risk in RA patients, the investigators found (Arthritis Care Res. 2014 July 29 [doi:10.1002/acr.22419]).

The researchers searched MEDLINE, EMBASE, CINAHL, Web of Science, and other sources to find 16,064 abstracts on CVD or RA since 2008 that mentioned guidelines or quality indicators. Of these, they fully reviewed 808 manuscripts, and scored 10 guidelines with the six-domain Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument, they said.

Only two guidelines recommended using a cardiovascular risk score, and only one, from the European League Against Rheumatism, suggested adjusting that score to account for RA, the researchers said. The guidelines also lacked thresholds for treating modifiable risk factors and did not clarify whether such thresholds should be lower than for the general population, they added.

Furthermore, the recommendations did clearly guide clinicians on monitoring or treating side effects of drugs such tocilizumab – which can cause dyslipidemia – and leflunomide, which can cause hypertension, said the investigators.

Levels of supporting evidence for guidelines also varied, and many recommendations lacked high-level evidence, particularly related to diet and exercise, the researchers said.

The four quality indicators included general screening for comorbidities, formal estimation of CVD risk, exercise, and minimizing use of steroids, the investigators said. The measures "did not cover the recognized breadth of CVD preventive care in RA," they added.

Future research should focus on how best to evaluate CVD risk in RA patients and should determine thresholds for lipid-lowering medications and other treatments, the investigators said. In the meantime, they recommended developing quality indicators for preventing CVD in RA based on the guidelines reviewed and on general population recommendations.

The research was supported by grants from Alberta Innovates Health Solutions, UCB Canada, the Canadian Rheumatology Association, and the Arthritis Society. The authors did not disclose conflicts of interest.

Rheumatoid arthritis increases cardiovascular risks as much as diabetes does, but guidelines and quality indicators fail to adequately address cardiovascular disease prevention for RA patients, authors of the first systematic review on the topic wrote in Arthritis Care & Research.

To date, only one guideline has focused entirely on the topic, and guidelines are too general to be used in adherence or quality improvement efforts, Dr. Claire Barber of the division of rheumatology at the University of Calgary (Alta.) and her associates reported. Furthermore, just four quality indicators have targeted CVD risk in RA patients, the investigators found (Arthritis Care Res. 2014 July 29 [doi:10.1002/acr.22419]).

The researchers searched MEDLINE, EMBASE, CINAHL, Web of Science, and other sources to find 16,064 abstracts on CVD or RA since 2008 that mentioned guidelines or quality indicators. Of these, they fully reviewed 808 manuscripts, and scored 10 guidelines with the six-domain Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument, they said.

Only two guidelines recommended using a cardiovascular risk score, and only one, from the European League Against Rheumatism, suggested adjusting that score to account for RA, the researchers said. The guidelines also lacked thresholds for treating modifiable risk factors and did not clarify whether such thresholds should be lower than for the general population, they added.

Furthermore, the recommendations did clearly guide clinicians on monitoring or treating side effects of drugs such tocilizumab – which can cause dyslipidemia – and leflunomide, which can cause hypertension, said the investigators.

Levels of supporting evidence for guidelines also varied, and many recommendations lacked high-level evidence, particularly related to diet and exercise, the researchers said.

The four quality indicators included general screening for comorbidities, formal estimation of CVD risk, exercise, and minimizing use of steroids, the investigators said. The measures "did not cover the recognized breadth of CVD preventive care in RA," they added.

Future research should focus on how best to evaluate CVD risk in RA patients and should determine thresholds for lipid-lowering medications and other treatments, the investigators said. In the meantime, they recommended developing quality indicators for preventing CVD in RA based on the guidelines reviewed and on general population recommendations.

The research was supported by grants from Alberta Innovates Health Solutions, UCB Canada, the Canadian Rheumatology Association, and the Arthritis Society. The authors did not disclose conflicts of interest.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

Some of the same factors that predict patients’ discontinuation of disease-modifying antirheumatic drugs for rheumatoid arthritis also appear to predict their initiation, such as use of oral glucocorticoids and Hispanic ethnicity, according to findings from a longitudinal cohort study.

It was "surprising" to lead investigator Dr. Daniel H. Solomon of Brigham and Women’s Hospital, Boston, and his associates that some of the same variables predicted both starting and stopping RA medication. "These factors may correlate with frequent treatment switches," they wrote. The fact that Hispanics were significantly more likely to start and to stop medication than non-Hispanics might reflect disparities in insurance coverage, differences in the availability of new treatments, or impaired communication about side effects because of language barriers, they added in their report published in Arthritis Care and Research.

Dr. Solomon and his colleagues based their analysis on data from the University of California, San Francisco, RA Panel study, a longitudinal cohort of 1,507 persons with rheumatoid arthritis (RA) who were randomly sampled from rheumatology practices in Northern California (Arthritis Care Res. 2014;66:1152-8). The study used a paired-years analysis to calculate percentages of patients who were on or off RA medications for a year and then either stopped or started medication the next year, the investigators said.

Of 1,974 pairs of years in which people were not on RA medication in year 1, they started medication the next year in 313 (15.9%) of the pairs. And of 7,595 pairs of years in which patients were taking medication in year 1, patients stopped all RA medications the next year in 423 (5.6%) of the pairs, the researchers reported.

In regression analyses, subjects were more likely to start medication when they were younger (odds ratio, 1.30; 95% confidence interval, 1.13-1.50/10-year decrease), Hispanic (OR, 1.88; 95% CI, 1.06-3.33), had RA for a shorter time (OR, 1.11; 95% CI, 1.01-1.22/5-year decrease), or were taking oral glucocorticoids (OR, 1.91; 95% CI, 1.36-2.67), the researchers said. Predictors of stopping RA drugs also included being younger (OR, 0.88; 95% CI, 0.80-0.98/decade decrease) or Hispanic (OR, 1.52; 95% CI, 1.02-2.30) and having the lowest annual income, compared with the highest income (OR, 1.83; 95% CI, 1.13-2.96), according to Dr. Solomon and his associates.

The "noteworthy" drop in RA drug discontinuation during the 23-year course of the study from 9% in 1986 to 3% in 2008 "may correlate with the increasing range of treatment options since the latter half of the 1990s. It may also be that rheumatologists have become less concerned about slightly abnormal laboratory results that occur occasionally by chance, for example, liver function tests among methotrexate users," the investigators suggested.

In contrast, no strong trends could be found for starting disease-modifying antirheumatic drugs during the study period.

"As health systems currently evolve with Medicaid expansions and a greater emphasis on primary care, reducing these barriers to appropriate care for patients with rheumatic disease will be an important goal," they concluded.

The study was funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some of the investigators reported receiving financial support from Amgen, the Consortium of Rheumatology Researchers of North America, Eli Lilly, and Pfizer.

Some of the same factors that predict patients’ discontinuation of disease-modifying antirheumatic drugs for rheumatoid arthritis also appear to predict their initiation, such as use of oral glucocorticoids and Hispanic ethnicity, according to findings from a longitudinal cohort study.

It was "surprising" to lead investigator Dr. Daniel H. Solomon of Brigham and Women’s Hospital, Boston, and his associates that some of the same variables predicted both starting and stopping RA medication. "These factors may correlate with frequent treatment switches," they wrote. The fact that Hispanics were significantly more likely to start and to stop medication than non-Hispanics might reflect disparities in insurance coverage, differences in the availability of new treatments, or impaired communication about side effects because of language barriers, they added in their report published in Arthritis Care and Research.

Dr. Solomon and his colleagues based their analysis on data from the University of California, San Francisco, RA Panel study, a longitudinal cohort of 1,507 persons with rheumatoid arthritis (RA) who were randomly sampled from rheumatology practices in Northern California (Arthritis Care Res. 2014;66:1152-8). The study used a paired-years analysis to calculate percentages of patients who were on or off RA medications for a year and then either stopped or started medication the next year, the investigators said.

Of 1,974 pairs of years in which people were not on RA medication in year 1, they started medication the next year in 313 (15.9%) of the pairs. And of 7,595 pairs of years in which patients were taking medication in year 1, patients stopped all RA medications the next year in 423 (5.6%) of the pairs, the researchers reported.

In regression analyses, subjects were more likely to start medication when they were younger (odds ratio, 1.30; 95% confidence interval, 1.13-1.50/10-year decrease), Hispanic (OR, 1.88; 95% CI, 1.06-3.33), had RA for a shorter time (OR, 1.11; 95% CI, 1.01-1.22/5-year decrease), or were taking oral glucocorticoids (OR, 1.91; 95% CI, 1.36-2.67), the researchers said. Predictors of stopping RA drugs also included being younger (OR, 0.88; 95% CI, 0.80-0.98/decade decrease) or Hispanic (OR, 1.52; 95% CI, 1.02-2.30) and having the lowest annual income, compared with the highest income (OR, 1.83; 95% CI, 1.13-2.96), according to Dr. Solomon and his associates.

The "noteworthy" drop in RA drug discontinuation during the 23-year course of the study from 9% in 1986 to 3% in 2008 "may correlate with the increasing range of treatment options since the latter half of the 1990s. It may also be that rheumatologists have become less concerned about slightly abnormal laboratory results that occur occasionally by chance, for example, liver function tests among methotrexate users," the investigators suggested.

In contrast, no strong trends could be found for starting disease-modifying antirheumatic drugs during the study period.

"As health systems currently evolve with Medicaid expansions and a greater emphasis on primary care, reducing these barriers to appropriate care for patients with rheumatic disease will be an important goal," they concluded.

The study was funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some of the investigators reported receiving financial support from Amgen, the Consortium of Rheumatology Researchers of North America, Eli Lilly, and Pfizer.

Some of the same factors that predict patients’ discontinuation of disease-modifying antirheumatic drugs for rheumatoid arthritis also appear to predict their initiation, such as use of oral glucocorticoids and Hispanic ethnicity, according to findings from a longitudinal cohort study.

It was "surprising" to lead investigator Dr. Daniel H. Solomon of Brigham and Women’s Hospital, Boston, and his associates that some of the same variables predicted both starting and stopping RA medication. "These factors may correlate with frequent treatment switches," they wrote. The fact that Hispanics were significantly more likely to start and to stop medication than non-Hispanics might reflect disparities in insurance coverage, differences in the availability of new treatments, or impaired communication about side effects because of language barriers, they added in their report published in Arthritis Care and Research.

Dr. Solomon and his colleagues based their analysis on data from the University of California, San Francisco, RA Panel study, a longitudinal cohort of 1,507 persons with rheumatoid arthritis (RA) who were randomly sampled from rheumatology practices in Northern California (Arthritis Care Res. 2014;66:1152-8). The study used a paired-years analysis to calculate percentages of patients who were on or off RA medications for a year and then either stopped or started medication the next year, the investigators said.

Of 1,974 pairs of years in which people were not on RA medication in year 1, they started medication the next year in 313 (15.9%) of the pairs. And of 7,595 pairs of years in which patients were taking medication in year 1, patients stopped all RA medications the next year in 423 (5.6%) of the pairs, the researchers reported.

In regression analyses, subjects were more likely to start medication when they were younger (odds ratio, 1.30; 95% confidence interval, 1.13-1.50/10-year decrease), Hispanic (OR, 1.88; 95% CI, 1.06-3.33), had RA for a shorter time (OR, 1.11; 95% CI, 1.01-1.22/5-year decrease), or were taking oral glucocorticoids (OR, 1.91; 95% CI, 1.36-2.67), the researchers said. Predictors of stopping RA drugs also included being younger (OR, 0.88; 95% CI, 0.80-0.98/decade decrease) or Hispanic (OR, 1.52; 95% CI, 1.02-2.30) and having the lowest annual income, compared with the highest income (OR, 1.83; 95% CI, 1.13-2.96), according to Dr. Solomon and his associates.

The "noteworthy" drop in RA drug discontinuation during the 23-year course of the study from 9% in 1986 to 3% in 2008 "may correlate with the increasing range of treatment options since the latter half of the 1990s. It may also be that rheumatologists have become less concerned about slightly abnormal laboratory results that occur occasionally by chance, for example, liver function tests among methotrexate users," the investigators suggested.

In contrast, no strong trends could be found for starting disease-modifying antirheumatic drugs during the study period.

"As health systems currently evolve with Medicaid expansions and a greater emphasis on primary care, reducing these barriers to appropriate care for patients with rheumatic disease will be an important goal," they concluded.

The study was funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some of the investigators reported receiving financial support from Amgen, the Consortium of Rheumatology Researchers of North America, Eli Lilly, and Pfizer.

The joints of patients with early arthritis that showed subclinical inflammation on MRI had an increased risk of radiographic progression in the first year after disease presentation, particularly those with bone marrow edema, according to findings from the first study to look at the radiographic outcome of such joints.

A total of 179 patients at the Leiden Early Arthritis Clinic, a population-based inception cohort including patients with confirmed clinical arthritis and symptoms for less than 2 years, underwent 1.5T extremity MRI at baseline of the metacarpophalangeal 2-5, wrist, and metatarsophalangeal 1-5 joints on the side with the most severe symptoms or the dominant side in cases in which both sides were equally affected. At 1-year follow-up, 113 had radiographs taken. Close to half of these patients (46.9%) fulfilled the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) at baseline, and those who did not have follow-up at 1 year were diagnosed with RA less often. Other patients had unclassified arthritis (32.7%), psoriatic arthritis (9.7%), inflammatory osteoarthritis (3.5%), spondylarthritis (2.7%), or other diagnoses (4.4%). Within the first year, 77% of all patients received treatment with a disease-modifying antirheumatic drug, including 93% of all patients with RA, said Dr. Annemarie Krabben and her colleagues at Leiden University Medical Center, the Netherlands (Ann. Rheum. Dis. 2014 July 29 [doi:10.1136/annrheumdis-2014-205208]).

Of the 1,130 joints studied, 932 were clinically free of swelling at baseline, and, of these, 232 (26%) had subclinical inflammation on MRI, including 17% with bone marrow edema, 16% with synovitis, and 21% with tenosynovitis. Overall, only 2% of the unswollen joints had radiographic progression at 1 year, compared with 8% of clinically swollen joints. The relative risk for radiographic progression in unswollen joints with subclinical inflammation on MRI was 3.5 (95% confidence interval, 1.3-9.6) based on radiographic progression in 4% of those with subclinical inflammation and 1% of those without it. The relative risk was highest for nonswollen joints with bone marrow edema (RR, 5.3; 95% CI, 2.0-14.0) and also significant for those with synovitis (RR, 3.4; 95% CI, 1.2-9.3), but not for those with tenosynovitis (RR, 3.0; 95% CI, 0.7-12.7). The relative risk was comparable for joints that were both nonswollen and nontender, although the 95% CI was broader.

"Our observation that the total level of MRI inflammation [in both swollen and unswollen joints] was an independent predictor for radiographic progression fits with previous findings," the investigators wrote. "Furthermore, our finding that subclinical inflammation at disease onset is associated with radiographic progression is in line with previous findings on subclinical inflammation in patients with RA in clinical remission."

The authors noted that their "study mainly increases the comprehension of the connection between inflammation and structural damage early in the disease. Whether subclinical MRI inflammation is relevant to clinical practice remains a question, as rheumatologists treat patients and not joints. Information on subclinical inflamed joints would affect treatment decisions most when patients have few clinically swollen joints."

The size of the study’s patient sample limits the applicability of the findings, particularly in regard to the moderate number of patients with RA, who had broad 95% CI estimates for the risk of radiographic progression. Other limits to the study included the relative infrequency of radiographic progression at 3% of all joints (4% of joints in patients with RA) and the relatively small increase of 1 or greater on the Sharp-van der Heijde score that was used to define radiographic progression.

The study was supported by the Dutch Arthritis Foundation, the Dutch Organization of Health Research and Development, the Center for Translational Molecular Medicine, and by a grant within the European Community Seventh Framework Programme FP7 (Masterswitch). The authors had no competing interests to declare.

jevans@frontlinemedcom.com

The joints of patients with early arthritis that showed subclinical inflammation on MRI had an increased risk of radiographic progression in the first year after disease presentation, particularly those with bone marrow edema, according to findings from the first study to look at the radiographic outcome of such joints.

A total of 179 patients at the Leiden Early Arthritis Clinic, a population-based inception cohort including patients with confirmed clinical arthritis and symptoms for less than 2 years, underwent 1.5T extremity MRI at baseline of the metacarpophalangeal 2-5, wrist, and metatarsophalangeal 1-5 joints on the side with the most severe symptoms or the dominant side in cases in which both sides were equally affected. At 1-year follow-up, 113 had radiographs taken. Close to half of these patients (46.9%) fulfilled the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) at baseline, and those who did not have follow-up at 1 year were diagnosed with RA less often. Other patients had unclassified arthritis (32.7%), psoriatic arthritis (9.7%), inflammatory osteoarthritis (3.5%), spondylarthritis (2.7%), or other diagnoses (4.4%). Within the first year, 77% of all patients received treatment with a disease-modifying antirheumatic drug, including 93% of all patients with RA, said Dr. Annemarie Krabben and her colleagues at Leiden University Medical Center, the Netherlands (Ann. Rheum. Dis. 2014 July 29 [doi:10.1136/annrheumdis-2014-205208]).

Of the 1,130 joints studied, 932 were clinically free of swelling at baseline, and, of these, 232 (26%) had subclinical inflammation on MRI, including 17% with bone marrow edema, 16% with synovitis, and 21% with tenosynovitis. Overall, only 2% of the unswollen joints had radiographic progression at 1 year, compared with 8% of clinically swollen joints. The relative risk for radiographic progression in unswollen joints with subclinical inflammation on MRI was 3.5 (95% confidence interval, 1.3-9.6) based on radiographic progression in 4% of those with subclinical inflammation and 1% of those without it. The relative risk was highest for nonswollen joints with bone marrow edema (RR, 5.3; 95% CI, 2.0-14.0) and also significant for those with synovitis (RR, 3.4; 95% CI, 1.2-9.3), but not for those with tenosynovitis (RR, 3.0; 95% CI, 0.7-12.7). The relative risk was comparable for joints that were both nonswollen and nontender, although the 95% CI was broader.

"Our observation that the total level of MRI inflammation [in both swollen and unswollen joints] was an independent predictor for radiographic progression fits with previous findings," the investigators wrote. "Furthermore, our finding that subclinical inflammation at disease onset is associated with radiographic progression is in line with previous findings on subclinical inflammation in patients with RA in clinical remission."

The authors noted that their "study mainly increases the comprehension of the connection between inflammation and structural damage early in the disease. Whether subclinical MRI inflammation is relevant to clinical practice remains a question, as rheumatologists treat patients and not joints. Information on subclinical inflamed joints would affect treatment decisions most when patients have few clinically swollen joints."

The size of the study’s patient sample limits the applicability of the findings, particularly in regard to the moderate number of patients with RA, who had broad 95% CI estimates for the risk of radiographic progression. Other limits to the study included the relative infrequency of radiographic progression at 3% of all joints (4% of joints in patients with RA) and the relatively small increase of 1 or greater on the Sharp-van der Heijde score that was used to define radiographic progression.

The study was supported by the Dutch Arthritis Foundation, the Dutch Organization of Health Research and Development, the Center for Translational Molecular Medicine, and by a grant within the European Community Seventh Framework Programme FP7 (Masterswitch). The authors had no competing interests to declare.

jevans@frontlinemedcom.com

The joints of patients with early arthritis that showed subclinical inflammation on MRI had an increased risk of radiographic progression in the first year after disease presentation, particularly those with bone marrow edema, according to findings from the first study to look at the radiographic outcome of such joints.

A total of 179 patients at the Leiden Early Arthritis Clinic, a population-based inception cohort including patients with confirmed clinical arthritis and symptoms for less than 2 years, underwent 1.5T extremity MRI at baseline of the metacarpophalangeal 2-5, wrist, and metatarsophalangeal 1-5 joints on the side with the most severe symptoms or the dominant side in cases in which both sides were equally affected. At 1-year follow-up, 113 had radiographs taken. Close to half of these patients (46.9%) fulfilled the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) at baseline, and those who did not have follow-up at 1 year were diagnosed with RA less often. Other patients had unclassified arthritis (32.7%), psoriatic arthritis (9.7%), inflammatory osteoarthritis (3.5%), spondylarthritis (2.7%), or other diagnoses (4.4%). Within the first year, 77% of all patients received treatment with a disease-modifying antirheumatic drug, including 93% of all patients with RA, said Dr. Annemarie Krabben and her colleagues at Leiden University Medical Center, the Netherlands (Ann. Rheum. Dis. 2014 July 29 [doi:10.1136/annrheumdis-2014-205208]).

Of the 1,130 joints studied, 932 were clinically free of swelling at baseline, and, of these, 232 (26%) had subclinical inflammation on MRI, including 17% with bone marrow edema, 16% with synovitis, and 21% with tenosynovitis. Overall, only 2% of the unswollen joints had radiographic progression at 1 year, compared with 8% of clinically swollen joints. The relative risk for radiographic progression in unswollen joints with subclinical inflammation on MRI was 3.5 (95% confidence interval, 1.3-9.6) based on radiographic progression in 4% of those with subclinical inflammation and 1% of those without it. The relative risk was highest for nonswollen joints with bone marrow edema (RR, 5.3; 95% CI, 2.0-14.0) and also significant for those with synovitis (RR, 3.4; 95% CI, 1.2-9.3), but not for those with tenosynovitis (RR, 3.0; 95% CI, 0.7-12.7). The relative risk was comparable for joints that were both nonswollen and nontender, although the 95% CI was broader.

"Our observation that the total level of MRI inflammation [in both swollen and unswollen joints] was an independent predictor for radiographic progression fits with previous findings," the investigators wrote. "Furthermore, our finding that subclinical inflammation at disease onset is associated with radiographic progression is in line with previous findings on subclinical inflammation in patients with RA in clinical remission."

The authors noted that their "study mainly increases the comprehension of the connection between inflammation and structural damage early in the disease. Whether subclinical MRI inflammation is relevant to clinical practice remains a question, as rheumatologists treat patients and not joints. Information on subclinical inflamed joints would affect treatment decisions most when patients have few clinically swollen joints."

The size of the study’s patient sample limits the applicability of the findings, particularly in regard to the moderate number of patients with RA, who had broad 95% CI estimates for the risk of radiographic progression. Other limits to the study included the relative infrequency of radiographic progression at 3% of all joints (4% of joints in patients with RA) and the relatively small increase of 1 or greater on the Sharp-van der Heijde score that was used to define radiographic progression.

The study was supported by the Dutch Arthritis Foundation, the Dutch Organization of Health Research and Development, the Center for Translational Molecular Medicine, and by a grant within the European Community Seventh Framework Programme FP7 (Masterswitch). The authors had no competing interests to declare.

jevans@frontlinemedcom.com

BELLEVUE, WASH. – The severity of rheumatoid arthritis early in pregnancy is an independent risk factor for preterm delivery, according to data from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project.

The prospective cohort study of 447 pregnant women with rheumatoid arthritis who had a live-born infant from 2005-2013 found that the greater disease severity before 20 weeks of gestation, assessed by a variety of measures, the higher the adjusted risk of delivering preterm. But there was no significant impact on the adjusted risk of having an infant small for gestational age or a cesarean section.

"Disease severity in women with rheumatoid arthritis, measured early in pregnancy, is predictive of preterm delivery," noted Dr. Balambal Bharti, a researcher at the bioscience center, University of California, San Diego, in presenting the findings at the annual meeting of the Teratology Society.

The investigators are performing additional analyses to determine whether disease severity at different times – early versus late pregnancy – has a similar or differing impact, and to assess any effect of a change in severity during pregnancy.

"For future research, we’d like to investigate if better disease management early in pregnancy improves pregnancy outcome," she said.

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University asked, "Did you know if there were differences in disease severity or treatment based on whether women had planned their pregnancies, and whether that could have affected your results? I’m just wondering if there are certain women who had planned their pregnancy and had changed their treatment regimen in anticipation of that."

"We didn’t know whether women had planned their pregnancies," Dr. Bharti replied, although some data suggest that about half of pregnancies in the Organization of Teratology Information Specialists cohort are unplanned. The investigators also did not look at whether women changed their treatment before conceiving, she said.

Session attendee Dr. Jan M. Freidman of the University of British Columbia in Vancouver noted, "Two of the three outcome variables you looked at are actually continuous variables: birth weight (or birth weight for gestational age) and week of gestation at which you deliver. As a clinician, it would be useful to know what the size of the effect was in terms of those continuous variables: How much did [disease severity] reduce birth weight? How much was the reduction, or was there a reduction, in gestational age? Did you look at the analysis in that way, or just in the discrete way you presented here?"

"All of our outcomes were dichotomized," Dr. Bharti replied.

"There is more information there that you might want to look at," Dr. Friedman recommended.

The women studied were administered the 4-point Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, before 20 weeks of gestation. They also rated their pain and global health in the past week on 100-point scales.

Overall, 15% of the women had a preterm delivery (one occurring before 37 weeks of gestation), 9% gave birth to an infant who was small for gestational age, and 42% had a cesarean section.

In multivariate adjusted analyses, women’s risk of preterm birth rose with each 1% increase (worsening) in HAQ-DI score (relative risk, 1.55) and with each 20-point increase (worsening) in pain score (RR, 1.17) and score on the global scale of overall health (RR,1.22).

In contrast, none of the three measures of disease severity independently predicted small for gestational age or cesarean delivery.

Dr. Bharti said that, to the authors’ knowledge, only one other prospective study has looked at the impact of rheumatoid arthritis disease severity on pregnancy outcomes (Arthritis Rheum. 2009;60:3196-206). That study followed white Dutch-speaking women in a first pregnancy who were taking prednisone, sulfasalazine, or hydroxychloroquine.

"Our study adds to [that study] by having women of diverse ethnic background who were in a first or subsequent pregnancy, and they were either on no treatment for rheumatoid arthritis or on any kind of treatment," she commented.

The new findings are generally similar to those of that previous study but differ in that they show a positive association between disease severity and preterm delivery, according to Dr. Bharti.

She disclosed no conflicts of interest related to the research.

BELLEVUE, WASH. – The severity of rheumatoid arthritis early in pregnancy is an independent risk factor for preterm delivery, according to data from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project.

The prospective cohort study of 447 pregnant women with rheumatoid arthritis who had a live-born infant from 2005-2013 found that the greater disease severity before 20 weeks of gestation, assessed by a variety of measures, the higher the adjusted risk of delivering preterm. But there was no significant impact on the adjusted risk of having an infant small for gestational age or a cesarean section.

"Disease severity in women with rheumatoid arthritis, measured early in pregnancy, is predictive of preterm delivery," noted Dr. Balambal Bharti, a researcher at the bioscience center, University of California, San Diego, in presenting the findings at the annual meeting of the Teratology Society.

The investigators are performing additional analyses to determine whether disease severity at different times – early versus late pregnancy – has a similar or differing impact, and to assess any effect of a change in severity during pregnancy.

"For future research, we’d like to investigate if better disease management early in pregnancy improves pregnancy outcome," she said.

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University asked, "Did you know if there were differences in disease severity or treatment based on whether women had planned their pregnancies, and whether that could have affected your results? I’m just wondering if there are certain women who had planned their pregnancy and had changed their treatment regimen in anticipation of that."

"We didn’t know whether women had planned their pregnancies," Dr. Bharti replied, although some data suggest that about half of pregnancies in the Organization of Teratology Information Specialists cohort are unplanned. The investigators also did not look at whether women changed their treatment before conceiving, she said.

Session attendee Dr. Jan M. Freidman of the University of British Columbia in Vancouver noted, "Two of the three outcome variables you looked at are actually continuous variables: birth weight (or birth weight for gestational age) and week of gestation at which you deliver. As a clinician, it would be useful to know what the size of the effect was in terms of those continuous variables: How much did [disease severity] reduce birth weight? How much was the reduction, or was there a reduction, in gestational age? Did you look at the analysis in that way, or just in the discrete way you presented here?"

"All of our outcomes were dichotomized," Dr. Bharti replied.

"There is more information there that you might want to look at," Dr. Friedman recommended.

The women studied were administered the 4-point Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, before 20 weeks of gestation. They also rated their pain and global health in the past week on 100-point scales.

Overall, 15% of the women had a preterm delivery (one occurring before 37 weeks of gestation), 9% gave birth to an infant who was small for gestational age, and 42% had a cesarean section.

In multivariate adjusted analyses, women’s risk of preterm birth rose with each 1% increase (worsening) in HAQ-DI score (relative risk, 1.55) and with each 20-point increase (worsening) in pain score (RR, 1.17) and score on the global scale of overall health (RR,1.22).

In contrast, none of the three measures of disease severity independently predicted small for gestational age or cesarean delivery.

Dr. Bharti said that, to the authors’ knowledge, only one other prospective study has looked at the impact of rheumatoid arthritis disease severity on pregnancy outcomes (Arthritis Rheum. 2009;60:3196-206). That study followed white Dutch-speaking women in a first pregnancy who were taking prednisone, sulfasalazine, or hydroxychloroquine.

"Our study adds to [that study] by having women of diverse ethnic background who were in a first or subsequent pregnancy, and they were either on no treatment for rheumatoid arthritis or on any kind of treatment," she commented.

The new findings are generally similar to those of that previous study but differ in that they show a positive association between disease severity and preterm delivery, according to Dr. Bharti.

She disclosed no conflicts of interest related to the research.

BELLEVUE, WASH. – The severity of rheumatoid arthritis early in pregnancy is an independent risk factor for preterm delivery, according to data from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project.

The prospective cohort study of 447 pregnant women with rheumatoid arthritis who had a live-born infant from 2005-2013 found that the greater disease severity before 20 weeks of gestation, assessed by a variety of measures, the higher the adjusted risk of delivering preterm. But there was no significant impact on the adjusted risk of having an infant small for gestational age or a cesarean section.

"Disease severity in women with rheumatoid arthritis, measured early in pregnancy, is predictive of preterm delivery," noted Dr. Balambal Bharti, a researcher at the bioscience center, University of California, San Diego, in presenting the findings at the annual meeting of the Teratology Society.

The investigators are performing additional analyses to determine whether disease severity at different times – early versus late pregnancy – has a similar or differing impact, and to assess any effect of a change in severity during pregnancy.

"For future research, we’d like to investigate if better disease management early in pregnancy improves pregnancy outcome," she said.

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University asked, "Did you know if there were differences in disease severity or treatment based on whether women had planned their pregnancies, and whether that could have affected your results? I’m just wondering if there are certain women who had planned their pregnancy and had changed their treatment regimen in anticipation of that."

"We didn’t know whether women had planned their pregnancies," Dr. Bharti replied, although some data suggest that about half of pregnancies in the Organization of Teratology Information Specialists cohort are unplanned. The investigators also did not look at whether women changed their treatment before conceiving, she said.

Session attendee Dr. Jan M. Freidman of the University of British Columbia in Vancouver noted, "Two of the three outcome variables you looked at are actually continuous variables: birth weight (or birth weight for gestational age) and week of gestation at which you deliver. As a clinician, it would be useful to know what the size of the effect was in terms of those continuous variables: How much did [disease severity] reduce birth weight? How much was the reduction, or was there a reduction, in gestational age? Did you look at the analysis in that way, or just in the discrete way you presented here?"

"All of our outcomes were dichotomized," Dr. Bharti replied.

"There is more information there that you might want to look at," Dr. Friedman recommended.

The women studied were administered the 4-point Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, before 20 weeks of gestation. They also rated their pain and global health in the past week on 100-point scales.

Overall, 15% of the women had a preterm delivery (one occurring before 37 weeks of gestation), 9% gave birth to an infant who was small for gestational age, and 42% had a cesarean section.

In multivariate adjusted analyses, women’s risk of preterm birth rose with each 1% increase (worsening) in HAQ-DI score (relative risk, 1.55) and with each 20-point increase (worsening) in pain score (RR, 1.17) and score on the global scale of overall health (RR,1.22).

In contrast, none of the three measures of disease severity independently predicted small for gestational age or cesarean delivery.

Dr. Bharti said that, to the authors’ knowledge, only one other prospective study has looked at the impact of rheumatoid arthritis disease severity on pregnancy outcomes (Arthritis Rheum. 2009;60:3196-206). That study followed white Dutch-speaking women in a first pregnancy who were taking prednisone, sulfasalazine, or hydroxychloroquine.

"Our study adds to [that study] by having women of diverse ethnic background who were in a first or subsequent pregnancy, and they were either on no treatment for rheumatoid arthritis or on any kind of treatment," she commented.

The new findings are generally similar to those of that previous study but differ in that they show a positive association between disease severity and preterm delivery, according to Dr. Bharti.

She disclosed no conflicts of interest related to the research.