Rheumatoid Arthritis

 A newly developed evidence-based set of recommendations and an algorithm for pharmacotherapy-based pain management in inflammatory arthritis achieved a high level of agreement among a multinational panel of rheumatologists who constitute the 2010 3e Initiative, according to a report presented by Dr. Samuel Whittle at the annual European Congress of Rheumatology.

The 3e (Evidence, Expertise, Exchange) Initiative is a multinational collaboration that aims to promote evidence-based medicine in rheumatology. For recommendations that address pain management by pharmacotherapy in inflammatory arthritis (IA), 89 of 453 rheumatologists from 17 countries who were involved in the initiative developed a list of 10 top clinical questions regarding medical treatment for IA pain.

Based on a systematic literature review performed for each question – ultimately including data from 167 relevant studies – rheumatologists from each country that was represented developed a set of national recommendations, and then multinational recommendations were formulated and assessed for agreement, reported Dr. Whittle of the Queen Elizabeth Hospital near Adelaide, Australia.

The panel made 11 recommendations in total. One of the original 10 questions was addressed by two separate systematic reviews. Six of the recommendations address the role of different analgesic medications, including combination therapy; two address pain-medication safety in patients with gastrointestinal, hepatic, renal, and cardiac comorbidities; one addresses pain measurement scales; one addresses pain management during the preconception period, pregnancy, and lactation; and one addresses the safety of analgesics in combination with methotrexate.

The level of agreement on the recommendations by the panel members ranged from 8.5 to 9.3 (mean, 8.9) on a 1- to 10-point scale.

"Although this level of agreement is quite high, it is not a particularly surprising finding," said Dr. Alexandra Colebatch, one of the authors of the report. Previous recommendations from the 3e initiative have had a mean level of agreement of 8.7 (range, 7.4-9.1) (Ann. Rheum. Dis. 2011;70:15-24) and 8.7 (range, 7.8-9.4) (Ann. Rheum. Dis. 2011;70:388-9)."

As for the algorithm developed for the pharmacologic management of pain, most (75%) of the rheumatologists said it was in accordance with their current practice, whereas 20% reported that it would change their practice, according to Dr. Whittle.

In addition to the main treatments to use in this patient population, the algorithm lists several points to consider, including type of pain, residual inflammation, comorbidities, patient preference, and addictive potential, and also includes adjuvant therapeutic options (such as tricyclic antidepressants and neuromodulators) to consider in these patients.

The evidence-based nature of these recommendations and the related algorithm, as well as the level of support demonstrated by the 3e initiative panel, suggest that they will have great utility in clinical practice, he concluded.

The individual systematic reviews are due to be published later this year, and the full recommendations and algorithm paper will be published soon, Dr. Colebatch said; 3e has previously addressed the investigation and follow-up of undifferentiated peripheral IA, and the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis, she noted.

The panel’s 11 recommendations for pharmacotherapy pain management in IA are the following:

• In patients with IA, pain should be measured routinely using one of the following validated scales: visual analogue scale, numerical rating scale, or verbal rating scale. In addition, consider multidimensional measures or site-specific tools as needed.

• Paracetamol is recommended for the treatment of persistent pain in patients with IA.

• Systemic glucocorticoids are not recommended for the routine management of pain in patients with IA in the absence of signs and symptoms of inflammation.

• In the treatment of pain in IA, tricyclic antidepressants and neuromodulators may be considered for use as adjuvant treatment; muscle relaxants and benzodiazepines cannot be recommended.

• Weak opioids may be used for short-term treatment of pain in patients with IA when other therapies have failed or are contraindicated; long-term use may be considered and should be regularly reviewed. Strong opioids should be used only in exceptional cases.

• In patients with an inadequate response to paracetamol or NSAID monotherapy, the addition of a drug with a different mode of action could be considered; combination of two or more NSAIDs should not be used.

• NSAIDs should be used at the lowest effective dose, either continuously or on demand, according to clinical circumstances.

• Existing guidance regarding the safety of pain pharmacotherapies during preconception, pregnancy, and lactation should be applied.

• In the management of patients with IA, methotrexate can be used safely in combination with standard doses of paracetamol and/or NSAIDs (excluding anti-inflammatory doses of aspirin).

• In patients with gastrointestinal comorbidities, paracetamol should be considered first. NSAIDs in combination with proton pump inhibitors (PPI), or coxibs with or without PPI, may be used with caution. In the presence of liver disease, standard precautions for use of NSAIDs and other analgesics should be applied.

• In patients with IA plus preexisting hypertension or cardiovascular or renal disease, paracetamol should be used first; NSAIDs (including coxibs) should be used with caution.

The 3e initiative is supported by an unrestricted educational grant from Abbot. Neither Dr. Whittle nor any other authors on this study had additional disclosures to report.

 A newly developed evidence-based set of recommendations and an algorithm for pharmacotherapy-based pain management in inflammatory arthritis achieved a high level of agreement among a multinational panel of rheumatologists who constitute the 2010 3e Initiative, according to a report presented by Dr. Samuel Whittle at the annual European Congress of Rheumatology.

The 3e (Evidence, Expertise, Exchange) Initiative is a multinational collaboration that aims to promote evidence-based medicine in rheumatology. For recommendations that address pain management by pharmacotherapy in inflammatory arthritis (IA), 89 of 453 rheumatologists from 17 countries who were involved in the initiative developed a list of 10 top clinical questions regarding medical treatment for IA pain.

Based on a systematic literature review performed for each question – ultimately including data from 167 relevant studies – rheumatologists from each country that was represented developed a set of national recommendations, and then multinational recommendations were formulated and assessed for agreement, reported Dr. Whittle of the Queen Elizabeth Hospital near Adelaide, Australia.

The panel made 11 recommendations in total. One of the original 10 questions was addressed by two separate systematic reviews. Six of the recommendations address the role of different analgesic medications, including combination therapy; two address pain-medication safety in patients with gastrointestinal, hepatic, renal, and cardiac comorbidities; one addresses pain measurement scales; one addresses pain management during the preconception period, pregnancy, and lactation; and one addresses the safety of analgesics in combination with methotrexate.

The level of agreement on the recommendations by the panel members ranged from 8.5 to 9.3 (mean, 8.9) on a 1- to 10-point scale.

"Although this level of agreement is quite high, it is not a particularly surprising finding," said Dr. Alexandra Colebatch, one of the authors of the report. Previous recommendations from the 3e initiative have had a mean level of agreement of 8.7 (range, 7.4-9.1) (Ann. Rheum. Dis. 2011;70:15-24) and 8.7 (range, 7.8-9.4) (Ann. Rheum. Dis. 2011;70:388-9)."

As for the algorithm developed for the pharmacologic management of pain, most (75%) of the rheumatologists said it was in accordance with their current practice, whereas 20% reported that it would change their practice, according to Dr. Whittle.

In addition to the main treatments to use in this patient population, the algorithm lists several points to consider, including type of pain, residual inflammation, comorbidities, patient preference, and addictive potential, and also includes adjuvant therapeutic options (such as tricyclic antidepressants and neuromodulators) to consider in these patients.

The evidence-based nature of these recommendations and the related algorithm, as well as the level of support demonstrated by the 3e initiative panel, suggest that they will have great utility in clinical practice, he concluded.

The individual systematic reviews are due to be published later this year, and the full recommendations and algorithm paper will be published soon, Dr. Colebatch said; 3e has previously addressed the investigation and follow-up of undifferentiated peripheral IA, and the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis, she noted.

The panel’s 11 recommendations for pharmacotherapy pain management in IA are the following:

• In patients with IA, pain should be measured routinely using one of the following validated scales: visual analogue scale, numerical rating scale, or verbal rating scale. In addition, consider multidimensional measures or site-specific tools as needed.

• Paracetamol is recommended for the treatment of persistent pain in patients with IA.

• Systemic glucocorticoids are not recommended for the routine management of pain in patients with IA in the absence of signs and symptoms of inflammation.

• In the treatment of pain in IA, tricyclic antidepressants and neuromodulators may be considered for use as adjuvant treatment; muscle relaxants and benzodiazepines cannot be recommended.

• Weak opioids may be used for short-term treatment of pain in patients with IA when other therapies have failed or are contraindicated; long-term use may be considered and should be regularly reviewed. Strong opioids should be used only in exceptional cases.

• In patients with an inadequate response to paracetamol or NSAID monotherapy, the addition of a drug with a different mode of action could be considered; combination of two or more NSAIDs should not be used.

• NSAIDs should be used at the lowest effective dose, either continuously or on demand, according to clinical circumstances.

• Existing guidance regarding the safety of pain pharmacotherapies during preconception, pregnancy, and lactation should be applied.

• In the management of patients with IA, methotrexate can be used safely in combination with standard doses of paracetamol and/or NSAIDs (excluding anti-inflammatory doses of aspirin).

• In patients with gastrointestinal comorbidities, paracetamol should be considered first. NSAIDs in combination with proton pump inhibitors (PPI), or coxibs with or without PPI, may be used with caution. In the presence of liver disease, standard precautions for use of NSAIDs and other analgesics should be applied.

• In patients with IA plus preexisting hypertension or cardiovascular or renal disease, paracetamol should be used first; NSAIDs (including coxibs) should be used with caution.

The 3e initiative is supported by an unrestricted educational grant from Abbot. Neither Dr. Whittle nor any other authors on this study had additional disclosures to report.

 A newly developed evidence-based set of recommendations and an algorithm for pharmacotherapy-based pain management in inflammatory arthritis achieved a high level of agreement among a multinational panel of rheumatologists who constitute the 2010 3e Initiative, according to a report presented by Dr. Samuel Whittle at the annual European Congress of Rheumatology.

The 3e (Evidence, Expertise, Exchange) Initiative is a multinational collaboration that aims to promote evidence-based medicine in rheumatology. For recommendations that address pain management by pharmacotherapy in inflammatory arthritis (IA), 89 of 453 rheumatologists from 17 countries who were involved in the initiative developed a list of 10 top clinical questions regarding medical treatment for IA pain.

Based on a systematic literature review performed for each question – ultimately including data from 167 relevant studies – rheumatologists from each country that was represented developed a set of national recommendations, and then multinational recommendations were formulated and assessed for agreement, reported Dr. Whittle of the Queen Elizabeth Hospital near Adelaide, Australia.

The panel made 11 recommendations in total. One of the original 10 questions was addressed by two separate systematic reviews. Six of the recommendations address the role of different analgesic medications, including combination therapy; two address pain-medication safety in patients with gastrointestinal, hepatic, renal, and cardiac comorbidities; one addresses pain measurement scales; one addresses pain management during the preconception period, pregnancy, and lactation; and one addresses the safety of analgesics in combination with methotrexate.

The level of agreement on the recommendations by the panel members ranged from 8.5 to 9.3 (mean, 8.9) on a 1- to 10-point scale.

"Although this level of agreement is quite high, it is not a particularly surprising finding," said Dr. Alexandra Colebatch, one of the authors of the report. Previous recommendations from the 3e initiative have had a mean level of agreement of 8.7 (range, 7.4-9.1) (Ann. Rheum. Dis. 2011;70:15-24) and 8.7 (range, 7.8-9.4) (Ann. Rheum. Dis. 2011;70:388-9)."

As for the algorithm developed for the pharmacologic management of pain, most (75%) of the rheumatologists said it was in accordance with their current practice, whereas 20% reported that it would change their practice, according to Dr. Whittle.

In addition to the main treatments to use in this patient population, the algorithm lists several points to consider, including type of pain, residual inflammation, comorbidities, patient preference, and addictive potential, and also includes adjuvant therapeutic options (such as tricyclic antidepressants and neuromodulators) to consider in these patients.

The evidence-based nature of these recommendations and the related algorithm, as well as the level of support demonstrated by the 3e initiative panel, suggest that they will have great utility in clinical practice, he concluded.

The individual systematic reviews are due to be published later this year, and the full recommendations and algorithm paper will be published soon, Dr. Colebatch said; 3e has previously addressed the investigation and follow-up of undifferentiated peripheral IA, and the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis, she noted.

The panel’s 11 recommendations for pharmacotherapy pain management in IA are the following:

• In patients with IA, pain should be measured routinely using one of the following validated scales: visual analogue scale, numerical rating scale, or verbal rating scale. In addition, consider multidimensional measures or site-specific tools as needed.

• Paracetamol is recommended for the treatment of persistent pain in patients with IA.

• Systemic glucocorticoids are not recommended for the routine management of pain in patients with IA in the absence of signs and symptoms of inflammation.

• In the treatment of pain in IA, tricyclic antidepressants and neuromodulators may be considered for use as adjuvant treatment; muscle relaxants and benzodiazepines cannot be recommended.

• Weak opioids may be used for short-term treatment of pain in patients with IA when other therapies have failed or are contraindicated; long-term use may be considered and should be regularly reviewed. Strong opioids should be used only in exceptional cases.

• In patients with an inadequate response to paracetamol or NSAID monotherapy, the addition of a drug with a different mode of action could be considered; combination of two or more NSAIDs should not be used.

• NSAIDs should be used at the lowest effective dose, either continuously or on demand, according to clinical circumstances.

• Existing guidance regarding the safety of pain pharmacotherapies during preconception, pregnancy, and lactation should be applied.

• In the management of patients with IA, methotrexate can be used safely in combination with standard doses of paracetamol and/or NSAIDs (excluding anti-inflammatory doses of aspirin).

• In patients with gastrointestinal comorbidities, paracetamol should be considered first. NSAIDs in combination with proton pump inhibitors (PPI), or coxibs with or without PPI, may be used with caution. In the presence of liver disease, standard precautions for use of NSAIDs and other analgesics should be applied.

• In patients with IA plus preexisting hypertension or cardiovascular or renal disease, paracetamol should be used first; NSAIDs (including coxibs) should be used with caution.

The 3e initiative is supported by an unrestricted educational grant from Abbot. Neither Dr. Whittle nor any other authors on this study had additional disclosures to report.

Magnetic resonance imaging is at least as sensitive as other modalities at predicting treatment response in patients with new onset spondyloarthritis, according to data presented on May 25 by Dr. Mikkel Østergaard at the annual European Congress of Rheumatology.

In discussing research that pointed to the usefulness of MRI in managing patients with ankylosing spondylitis (SpA), Dr. Østergaard reviewed the varied manifestations SpA can take on MRI, and how imaging can be a useful tool for predicting the formation of new bone.

“MRI has brought a major improvement in the evaluation and management of patients with spondyloarthritis,” he said. “It allows earlier detection of sacroiliitis than [does] any other modality, and has thereby enabled physicians to diagnose spondyloarthritis up to 5-10 years earlier than they could before.” He added that MRI provides physicians with an objective way to monitor disease activity in SpA.

Dr. Østergaard explained how to use MRI to identify disease in the sacroiliac joints, the spine, and the peripheral joints. “Given the major improvement in evaluation and management of spondyloarthritis patients that MRI has brought, it is very important that rheumatologists are aware of the findings that indicate actual spondyloarthritis and of the advantages of MRI so that they can order the correct examinations,” he said.

“It is important that not only rheumatologists but also radiologists are aware of the large impact of early diagnosis and treatment of patients with SpA concerning pain relief and better function,” he noted. Radiologists should prioritize to do early and adequate MRI examinations in patients with suspected spondyloarthritis. Ordering MRI “at an earlier and more appropriate phase in the patient’s disease” could help those patients get a quick diagnosis and allow early initiation of the relevant therapy, Dr. Østergaard added.

He discussed a study in which he participated that involved 50 patients with SpA who had an MRI done once at baseline and again on follow-up at an average of 19.2 months later. Patients also underwent spinal radiography at baseline and follow-up more than 2 years later. The goal of the study was to use imaging to evaluate the effectiveness of anti–tumor necrosis factor (TNF)–alpha agents for treatment of vertebral corner inflammatory lesions. The study aimed to evaluate whether MRI could be used to predict the growth of new syndesmophytes after anti-TNF-alpha therapy, said Dr. Østergaard of the department of rheumatology at the University of Copenhagen and Glostrup (Denmark) Hospital, who was a coauthor.

The study showed that in patients who receive anti-TNF-alpha therapy, new syndesmophytes developed more frequently from vertebral corners where follow-up MRI had shown a completely resolved corner inflammatory lesion, compared with vertebral corners with no inflammatory lesions (42.9 % vs. 2.4 %). For patients who received standard treatment, the study reported a similar pattern (20 % vs. 3.3 %), he added.

The study findings indicated that MRI can predict new bone formation on radiograph, and supported the theory that anti-TNF-alpha acts to inhibit new bone formation. However, because the sample size was so small, further study will be needed to validate these findings, Dr. Østergaard said.

Dr. Østergaard had no disclosures to report.

Magnetic resonance imaging is at least as sensitive as other modalities at predicting treatment response in patients with new onset spondyloarthritis, according to data presented on May 25 by Dr. Mikkel Østergaard at the annual European Congress of Rheumatology.

In discussing research that pointed to the usefulness of MRI in managing patients with ankylosing spondylitis (SpA), Dr. Østergaard reviewed the varied manifestations SpA can take on MRI, and how imaging can be a useful tool for predicting the formation of new bone.

“MRI has brought a major improvement in the evaluation and management of patients with spondyloarthritis,” he said. “It allows earlier detection of sacroiliitis than [does] any other modality, and has thereby enabled physicians to diagnose spondyloarthritis up to 5-10 years earlier than they could before.” He added that MRI provides physicians with an objective way to monitor disease activity in SpA.

Dr. Østergaard explained how to use MRI to identify disease in the sacroiliac joints, the spine, and the peripheral joints. “Given the major improvement in evaluation and management of spondyloarthritis patients that MRI has brought, it is very important that rheumatologists are aware of the findings that indicate actual spondyloarthritis and of the advantages of MRI so that they can order the correct examinations,” he said.

“It is important that not only rheumatologists but also radiologists are aware of the large impact of early diagnosis and treatment of patients with SpA concerning pain relief and better function,” he noted. Radiologists should prioritize to do early and adequate MRI examinations in patients with suspected spondyloarthritis. Ordering MRI “at an earlier and more appropriate phase in the patient’s disease” could help those patients get a quick diagnosis and allow early initiation of the relevant therapy, Dr. Østergaard added.

He discussed a study in which he participated that involved 50 patients with SpA who had an MRI done once at baseline and again on follow-up at an average of 19.2 months later. Patients also underwent spinal radiography at baseline and follow-up more than 2 years later. The goal of the study was to use imaging to evaluate the effectiveness of anti–tumor necrosis factor (TNF)–alpha agents for treatment of vertebral corner inflammatory lesions. The study aimed to evaluate whether MRI could be used to predict the growth of new syndesmophytes after anti-TNF-alpha therapy, said Dr. Østergaard of the department of rheumatology at the University of Copenhagen and Glostrup (Denmark) Hospital, who was a coauthor.

The study showed that in patients who receive anti-TNF-alpha therapy, new syndesmophytes developed more frequently from vertebral corners where follow-up MRI had shown a completely resolved corner inflammatory lesion, compared with vertebral corners with no inflammatory lesions (42.9 % vs. 2.4 %). For patients who received standard treatment, the study reported a similar pattern (20 % vs. 3.3 %), he added.

The study findings indicated that MRI can predict new bone formation on radiograph, and supported the theory that anti-TNF-alpha acts to inhibit new bone formation. However, because the sample size was so small, further study will be needed to validate these findings, Dr. Østergaard said.

Dr. Østergaard had no disclosures to report.

Magnetic resonance imaging is at least as sensitive as other modalities at predicting treatment response in patients with new onset spondyloarthritis, according to data presented on May 25 by Dr. Mikkel Østergaard at the annual European Congress of Rheumatology.

In discussing research that pointed to the usefulness of MRI in managing patients with ankylosing spondylitis (SpA), Dr. Østergaard reviewed the varied manifestations SpA can take on MRI, and how imaging can be a useful tool for predicting the formation of new bone.

“MRI has brought a major improvement in the evaluation and management of patients with spondyloarthritis,” he said. “It allows earlier detection of sacroiliitis than [does] any other modality, and has thereby enabled physicians to diagnose spondyloarthritis up to 5-10 years earlier than they could before.” He added that MRI provides physicians with an objective way to monitor disease activity in SpA.

Dr. Østergaard explained how to use MRI to identify disease in the sacroiliac joints, the spine, and the peripheral joints. “Given the major improvement in evaluation and management of spondyloarthritis patients that MRI has brought, it is very important that rheumatologists are aware of the findings that indicate actual spondyloarthritis and of the advantages of MRI so that they can order the correct examinations,” he said.

“It is important that not only rheumatologists but also radiologists are aware of the large impact of early diagnosis and treatment of patients with SpA concerning pain relief and better function,” he noted. Radiologists should prioritize to do early and adequate MRI examinations in patients with suspected spondyloarthritis. Ordering MRI “at an earlier and more appropriate phase in the patient’s disease” could help those patients get a quick diagnosis and allow early initiation of the relevant therapy, Dr. Østergaard added.

He discussed a study in which he participated that involved 50 patients with SpA who had an MRI done once at baseline and again on follow-up at an average of 19.2 months later. Patients also underwent spinal radiography at baseline and follow-up more than 2 years later. The goal of the study was to use imaging to evaluate the effectiveness of anti–tumor necrosis factor (TNF)–alpha agents for treatment of vertebral corner inflammatory lesions. The study aimed to evaluate whether MRI could be used to predict the growth of new syndesmophytes after anti-TNF-alpha therapy, said Dr. Østergaard of the department of rheumatology at the University of Copenhagen and Glostrup (Denmark) Hospital, who was a coauthor.

The study showed that in patients who receive anti-TNF-alpha therapy, new syndesmophytes developed more frequently from vertebral corners where follow-up MRI had shown a completely resolved corner inflammatory lesion, compared with vertebral corners with no inflammatory lesions (42.9 % vs. 2.4 %). For patients who received standard treatment, the study reported a similar pattern (20 % vs. 3.3 %), he added.

The study findings indicated that MRI can predict new bone formation on radiograph, and supported the theory that anti-TNF-alpha acts to inhibit new bone formation. However, because the sample size was so small, further study will be needed to validate these findings, Dr. Østergaard said.

Dr. Østergaard had no disclosures to report.

Patients with rheumatoid arthritis who received 3 months of treatment with the investigational Janus kinase inhibitor tofacitinib had clinically significant improvements in patient-reported outcomes, compared with those who were given placebo, according to Dr. Vibeke Strand, who reported the 3-month results of a 6-month, phase III trial on May 26.

"I see this drug as being everything that a biologic is. ...There are a lot of places where biologics are not very accessible. ... The data look quite comparable to biologics," Dr. Strand said in an interview.

The study marks the first of five pivotal, phase III, randomized, placebo-controlled trials planned for tofacitinib (CP-690-550), Dr. Strand said in an interview. She described tofacitinib as "the first of several Janus kinase and Syk kinase inhibitors that are promising oral disease-modifying antirheumatic drugs with onset of effect that is rapid and magnitude of effect similar to anti–[tumor necrosis factor] therapies," said Dr. Strand of the division of immunology/rheumatology at Stanford (Calif.) University. Tofacitinib "has been studied vs. monotherapy adalimumab in phase II."

For the current 6-month trial, 610 rheumatoid arthritis (RA) patients were randomized to one of three treatments: tofacitinib 5 mg b.i.d., tofacitinib 10 mg b.i.d., or placebo, all as monotherapy. Patients on placebo were advanced to either tofacitinib 5 mg b.i.d. or tofacitinib 10 mg b.i.d. after month 3. The mean age of the patients was 51 years, and 87% were women.

In her presentation, Dr. Strand reported change-from-baseline results on several patient-reported outcomes at 3 months, including Patient Global Assessment of disease activity on a visual analog scale, pain on a visual analog scale, physical function by the HAQ-DI (Health Assessment Questionnaire–Disability Index), and health-related quality of life by the MOS SF-36 (Medical Outcomes Study 36-item Short Form Health Survey).

Improvements were reported as least square means of changes from baseline. At 3 months, treatment with tofacitinib monotherapy resulted in statistically significant and clinically meaningful improvements, compared with placebo, in all patient-reported outcomes except sleep improvement in the tofacitinib 5-mg group.

Mean Patient Global Assessment scores achieved a minimally clinically important difference (MCID) relative to baseline in 73% of the patients taking 5 mg (number needed to treat, 4), in 75% of patients taking10 mg (NNT, 3.8), and in 48% of the placebo group.

Patients’ pain scores showed an MCID relative to baseline in 70% of the patients on 5 mg (NNT, 4.6), in 77% of the patients on 10 mg (NNT, 3.5), and in 48% of the patients on placebo.

Physical function scores on the HAQ-DI showed an MCID relative to baseline in 61% of the patients on 5 mg (NNT, 5.7), in 68% in patients taking 10 mg (NNT, 4), and in 43% of those on placebo.

The physical component scores on the MOS SF-36 were 2.63, 6.97, and 8.55, respectively. Physical component scores on the MOS SF-36 showed an MCID relative to baseline in 68% of the patients on 5 mg (NNT, 4.2), in 75% of the group on 10 mg (NNT, 3.2), and in 44% of those on placebo.

"Randomized, controlled trial data don’t always reflect what we see in the clinic, but this product has a large phase II database, and these findings are consistent with those data," Dr. Strand said. "Patients clearly have derived early and clinically meaningful benefit from treatment – in pain, fatigue, physical function, and ‘multidimensional function’ [as shown] in the SF-36 – which reflects improvements in those parameters, and not just physical and emotional well-being but also in social functioning and mental health."

Dr. Strand disclosed that she is a paid consultant to Pfizer but said that she received no support for preparation of the abstract or presentation.

Patients with rheumatoid arthritis who received 3 months of treatment with the investigational Janus kinase inhibitor tofacitinib had clinically significant improvements in patient-reported outcomes, compared with those who were given placebo, according to Dr. Vibeke Strand, who reported the 3-month results of a 6-month, phase III trial on May 26.

"I see this drug as being everything that a biologic is. ...There are a lot of places where biologics are not very accessible. ... The data look quite comparable to biologics," Dr. Strand said in an interview.

The study marks the first of five pivotal, phase III, randomized, placebo-controlled trials planned for tofacitinib (CP-690-550), Dr. Strand said in an interview. She described tofacitinib as "the first of several Janus kinase and Syk kinase inhibitors that are promising oral disease-modifying antirheumatic drugs with onset of effect that is rapid and magnitude of effect similar to anti–[tumor necrosis factor] therapies," said Dr. Strand of the division of immunology/rheumatology at Stanford (Calif.) University. Tofacitinib "has been studied vs. monotherapy adalimumab in phase II."

For the current 6-month trial, 610 rheumatoid arthritis (RA) patients were randomized to one of three treatments: tofacitinib 5 mg b.i.d., tofacitinib 10 mg b.i.d., or placebo, all as monotherapy. Patients on placebo were advanced to either tofacitinib 5 mg b.i.d. or tofacitinib 10 mg b.i.d. after month 3. The mean age of the patients was 51 years, and 87% were women.

In her presentation, Dr. Strand reported change-from-baseline results on several patient-reported outcomes at 3 months, including Patient Global Assessment of disease activity on a visual analog scale, pain on a visual analog scale, physical function by the HAQ-DI (Health Assessment Questionnaire–Disability Index), and health-related quality of life by the MOS SF-36 (Medical Outcomes Study 36-item Short Form Health Survey).

Improvements were reported as least square means of changes from baseline. At 3 months, treatment with tofacitinib monotherapy resulted in statistically significant and clinically meaningful improvements, compared with placebo, in all patient-reported outcomes except sleep improvement in the tofacitinib 5-mg group.

Mean Patient Global Assessment scores achieved a minimally clinically important difference (MCID) relative to baseline in 73% of the patients taking 5 mg (number needed to treat, 4), in 75% of patients taking10 mg (NNT, 3.8), and in 48% of the placebo group.

Patients’ pain scores showed an MCID relative to baseline in 70% of the patients on 5 mg (NNT, 4.6), in 77% of the patients on 10 mg (NNT, 3.5), and in 48% of the patients on placebo.

Physical function scores on the HAQ-DI showed an MCID relative to baseline in 61% of the patients on 5 mg (NNT, 5.7), in 68% in patients taking 10 mg (NNT, 4), and in 43% of those on placebo.

The physical component scores on the MOS SF-36 were 2.63, 6.97, and 8.55, respectively. Physical component scores on the MOS SF-36 showed an MCID relative to baseline in 68% of the patients on 5 mg (NNT, 4.2), in 75% of the group on 10 mg (NNT, 3.2), and in 44% of those on placebo.

"Randomized, controlled trial data don’t always reflect what we see in the clinic, but this product has a large phase II database, and these findings are consistent with those data," Dr. Strand said. "Patients clearly have derived early and clinically meaningful benefit from treatment – in pain, fatigue, physical function, and ‘multidimensional function’ [as shown] in the SF-36 – which reflects improvements in those parameters, and not just physical and emotional well-being but also in social functioning and mental health."

Dr. Strand disclosed that she is a paid consultant to Pfizer but said that she received no support for preparation of the abstract or presentation.

Patients with rheumatoid arthritis who received 3 months of treatment with the investigational Janus kinase inhibitor tofacitinib had clinically significant improvements in patient-reported outcomes, compared with those who were given placebo, according to Dr. Vibeke Strand, who reported the 3-month results of a 6-month, phase III trial on May 26.

"I see this drug as being everything that a biologic is. ...There are a lot of places where biologics are not very accessible. ... The data look quite comparable to biologics," Dr. Strand said in an interview.

The study marks the first of five pivotal, phase III, randomized, placebo-controlled trials planned for tofacitinib (CP-690-550), Dr. Strand said in an interview. She described tofacitinib as "the first of several Janus kinase and Syk kinase inhibitors that are promising oral disease-modifying antirheumatic drugs with onset of effect that is rapid and magnitude of effect similar to anti–[tumor necrosis factor] therapies," said Dr. Strand of the division of immunology/rheumatology at Stanford (Calif.) University. Tofacitinib "has been studied vs. monotherapy adalimumab in phase II."

For the current 6-month trial, 610 rheumatoid arthritis (RA) patients were randomized to one of three treatments: tofacitinib 5 mg b.i.d., tofacitinib 10 mg b.i.d., or placebo, all as monotherapy. Patients on placebo were advanced to either tofacitinib 5 mg b.i.d. or tofacitinib 10 mg b.i.d. after month 3. The mean age of the patients was 51 years, and 87% were women.

In her presentation, Dr. Strand reported change-from-baseline results on several patient-reported outcomes at 3 months, including Patient Global Assessment of disease activity on a visual analog scale, pain on a visual analog scale, physical function by the HAQ-DI (Health Assessment Questionnaire–Disability Index), and health-related quality of life by the MOS SF-36 (Medical Outcomes Study 36-item Short Form Health Survey).

Improvements were reported as least square means of changes from baseline. At 3 months, treatment with tofacitinib monotherapy resulted in statistically significant and clinically meaningful improvements, compared with placebo, in all patient-reported outcomes except sleep improvement in the tofacitinib 5-mg group.

Mean Patient Global Assessment scores achieved a minimally clinically important difference (MCID) relative to baseline in 73% of the patients taking 5 mg (number needed to treat, 4), in 75% of patients taking10 mg (NNT, 3.8), and in 48% of the placebo group.

Patients’ pain scores showed an MCID relative to baseline in 70% of the patients on 5 mg (NNT, 4.6), in 77% of the patients on 10 mg (NNT, 3.5), and in 48% of the patients on placebo.

Physical function scores on the HAQ-DI showed an MCID relative to baseline in 61% of the patients on 5 mg (NNT, 5.7), in 68% in patients taking 10 mg (NNT, 4), and in 43% of those on placebo.

The physical component scores on the MOS SF-36 were 2.63, 6.97, and 8.55, respectively. Physical component scores on the MOS SF-36 showed an MCID relative to baseline in 68% of the patients on 5 mg (NNT, 4.2), in 75% of the group on 10 mg (NNT, 3.2), and in 44% of those on placebo.

"Randomized, controlled trial data don’t always reflect what we see in the clinic, but this product has a large phase II database, and these findings are consistent with those data," Dr. Strand said. "Patients clearly have derived early and clinically meaningful benefit from treatment – in pain, fatigue, physical function, and ‘multidimensional function’ [as shown] in the SF-36 – which reflects improvements in those parameters, and not just physical and emotional well-being but also in social functioning and mental health."

Dr. Strand disclosed that she is a paid consultant to Pfizer but said that she received no support for preparation of the abstract or presentation.

The addition of low-dose prednisone to a methotrexate-based, tight-control strategy leads to better outcomes in early rheumatoid arthritis, according to results from the CAMERA-II trial reported by Marije F. Bakker, Ph.D.

Compared with patients who received methotrexate (MTX) with placebo, those receiving MTX with 10-mg/day prednisone had better control of their disease and less erosive damage to their joints, Dr. Bakker said in an interview.

"The existing strategies leave room for improvement, especially for the number of patients who reach remission," said Dr. Bakker of University Medical Center Utrecht (the Netherlands) in explaining the study’s rationale. "Besides, it is important to determine which strategy steps are useful in the tight-control treatment strategies. Also, it is important to decide at which moment early in the treatment of [rheumatoid arthritis] medication should be added to the strategy."

The CAMERA-II (Computer-Assisted Management of Early Rheumatoid Arthritis–II) trialwas designed specifically to test the hypothesis that the addition of prednisone to a tight-control strategy of early RA using disease-modifying antirheumatic drugs would result in better disease control.

In the randomized, double-blind, placebo-controlled trial, 117 patients received MTX plus prednisone and 119 received MTX with placebo. All patients had early RA, with an onset less than 1 year before enrollment. Patients were at least 18 years old and had no previous DMARD therapy.

Patients were excluded from the trial if they had major comorbidities such as malignancies or severe diabetes mellitus; abnormal liver or kidney function; leukopenia or thrombocytopenia; evidence of drug or alcohol abuse; treatment with cytotoxic or immunosuppressive drugs within 3 months of the study; or osteoporotic vertebral fractures.

Investigators tailored the MTX treatment to each patient with the goal of achieving remission. If patients did not achieve remission with the maximum tolerable oral MTX dose, investigators first switched the patient to subcutaneous MTX and then added adalimumab to the regimen.

After 2 years, patients in the MTX plus prednisone group had significantly less radiographically confirmed erosive joint damage, as measured by their Sharp/van der Heijde scores. Patients on the MTX with prednisone regimen had significantly lower scores on the DAS28 (Disease Activity Score using a 28-joint count) questionnaire, and lower disability scores on the HAQ (Health Assessment Questionnaire).

A significantly lower proportion of patients in the experimental group required biologic treatment, compared with those on placebo (14% vs. 36%). The time to sustained remission was 6 months in the experimental group and 11 months in the control group, a significant difference. In addition, patients in the experimental group appeared to be somewhat more likely to achieve sustained remission, although this result did not achieve statistical significance (72% vs. 61%; P = .09).

Rates of adverse events were similar (29% in the MTX-prednisone group and 35% in the MTX-placebo group).

The trial was supported by the University Medical Center Utrecht and by Abbott. Dr. Bakker stated that she had no relevant financial disclosures.

The addition of low-dose prednisone to a methotrexate-based, tight-control strategy leads to better outcomes in early rheumatoid arthritis, according to results from the CAMERA-II trial reported by Marije F. Bakker, Ph.D.

Compared with patients who received methotrexate (MTX) with placebo, those receiving MTX with 10-mg/day prednisone had better control of their disease and less erosive damage to their joints, Dr. Bakker said in an interview.

"The existing strategies leave room for improvement, especially for the number of patients who reach remission," said Dr. Bakker of University Medical Center Utrecht (the Netherlands) in explaining the study’s rationale. "Besides, it is important to determine which strategy steps are useful in the tight-control treatment strategies. Also, it is important to decide at which moment early in the treatment of [rheumatoid arthritis] medication should be added to the strategy."

The CAMERA-II (Computer-Assisted Management of Early Rheumatoid Arthritis–II) trialwas designed specifically to test the hypothesis that the addition of prednisone to a tight-control strategy of early RA using disease-modifying antirheumatic drugs would result in better disease control.

In the randomized, double-blind, placebo-controlled trial, 117 patients received MTX plus prednisone and 119 received MTX with placebo. All patients had early RA, with an onset less than 1 year before enrollment. Patients were at least 18 years old and had no previous DMARD therapy.

Patients were excluded from the trial if they had major comorbidities such as malignancies or severe diabetes mellitus; abnormal liver or kidney function; leukopenia or thrombocytopenia; evidence of drug or alcohol abuse; treatment with cytotoxic or immunosuppressive drugs within 3 months of the study; or osteoporotic vertebral fractures.

Investigators tailored the MTX treatment to each patient with the goal of achieving remission. If patients did not achieve remission with the maximum tolerable oral MTX dose, investigators first switched the patient to subcutaneous MTX and then added adalimumab to the regimen.

After 2 years, patients in the MTX plus prednisone group had significantly less radiographically confirmed erosive joint damage, as measured by their Sharp/van der Heijde scores. Patients on the MTX with prednisone regimen had significantly lower scores on the DAS28 (Disease Activity Score using a 28-joint count) questionnaire, and lower disability scores on the HAQ (Health Assessment Questionnaire).

A significantly lower proportion of patients in the experimental group required biologic treatment, compared with those on placebo (14% vs. 36%). The time to sustained remission was 6 months in the experimental group and 11 months in the control group, a significant difference. In addition, patients in the experimental group appeared to be somewhat more likely to achieve sustained remission, although this result did not achieve statistical significance (72% vs. 61%; P = .09).

Rates of adverse events were similar (29% in the MTX-prednisone group and 35% in the MTX-placebo group).

The trial was supported by the University Medical Center Utrecht and by Abbott. Dr. Bakker stated that she had no relevant financial disclosures.

The addition of low-dose prednisone to a methotrexate-based, tight-control strategy leads to better outcomes in early rheumatoid arthritis, according to results from the CAMERA-II trial reported by Marije F. Bakker, Ph.D.

Compared with patients who received methotrexate (MTX) with placebo, those receiving MTX with 10-mg/day prednisone had better control of their disease and less erosive damage to their joints, Dr. Bakker said in an interview.

"The existing strategies leave room for improvement, especially for the number of patients who reach remission," said Dr. Bakker of University Medical Center Utrecht (the Netherlands) in explaining the study’s rationale. "Besides, it is important to determine which strategy steps are useful in the tight-control treatment strategies. Also, it is important to decide at which moment early in the treatment of [rheumatoid arthritis] medication should be added to the strategy."

The CAMERA-II (Computer-Assisted Management of Early Rheumatoid Arthritis–II) trialwas designed specifically to test the hypothesis that the addition of prednisone to a tight-control strategy of early RA using disease-modifying antirheumatic drugs would result in better disease control.

In the randomized, double-blind, placebo-controlled trial, 117 patients received MTX plus prednisone and 119 received MTX with placebo. All patients had early RA, with an onset less than 1 year before enrollment. Patients were at least 18 years old and had no previous DMARD therapy.

Patients were excluded from the trial if they had major comorbidities such as malignancies or severe diabetes mellitus; abnormal liver or kidney function; leukopenia or thrombocytopenia; evidence of drug or alcohol abuse; treatment with cytotoxic or immunosuppressive drugs within 3 months of the study; or osteoporotic vertebral fractures.

Investigators tailored the MTX treatment to each patient with the goal of achieving remission. If patients did not achieve remission with the maximum tolerable oral MTX dose, investigators first switched the patient to subcutaneous MTX and then added adalimumab to the regimen.

After 2 years, patients in the MTX plus prednisone group had significantly less radiographically confirmed erosive joint damage, as measured by their Sharp/van der Heijde scores. Patients on the MTX with prednisone regimen had significantly lower scores on the DAS28 (Disease Activity Score using a 28-joint count) questionnaire, and lower disability scores on the HAQ (Health Assessment Questionnaire).

A significantly lower proportion of patients in the experimental group required biologic treatment, compared with those on placebo (14% vs. 36%). The time to sustained remission was 6 months in the experimental group and 11 months in the control group, a significant difference. In addition, patients in the experimental group appeared to be somewhat more likely to achieve sustained remission, although this result did not achieve statistical significance (72% vs. 61%; P = .09).

Rates of adverse events were similar (29% in the MTX-prednisone group and 35% in the MTX-placebo group).

The trial was supported by the University Medical Center Utrecht and by Abbott. Dr. Bakker stated that she had no relevant financial disclosures.

Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.

For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the annual European Congress of Rheumatology, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå (Sweden) University, the scheduled presenter who was unable to attend.

(c) Suprijono Suharjoto/Fotolia.com

The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapää Dahlqvist, also of Umeå University.

The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.

The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.

The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%). Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.

"The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor" in univariate but not multivariate analysis, they noted.

Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.

Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001). The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.

The findings show that first-degree relatives can have detectable amounts of autoantibodies, but may lack some other risk factors (such as SE or smoking) and still remain healthy. Another possibility is that they have particular as-yet-unidentified protective factors, the investigators said, adding that a follow-up study would be useful to help determine which of the isotypes provides the most information about disease progression and would thus be most important to analyze to help identify relatives likely to be affected by RA.

The investigators said they had no relevant financial disclosures.

Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.

For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the annual European Congress of Rheumatology, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå (Sweden) University, the scheduled presenter who was unable to attend.

(c) Suprijono Suharjoto/Fotolia.com

The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapää Dahlqvist, also of Umeå University.

The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.

The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.

The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%). Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.

"The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor" in univariate but not multivariate analysis, they noted.

Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.

Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001). The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.

The findings show that first-degree relatives can have detectable amounts of autoantibodies, but may lack some other risk factors (such as SE or smoking) and still remain healthy. Another possibility is that they have particular as-yet-unidentified protective factors, the investigators said, adding that a follow-up study would be useful to help determine which of the isotypes provides the most information about disease progression and would thus be most important to analyze to help identify relatives likely to be affected by RA.

The investigators said they had no relevant financial disclosures.

Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.

For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the annual European Congress of Rheumatology, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå (Sweden) University, the scheduled presenter who was unable to attend.

(c) Suprijono Suharjoto/Fotolia.com

The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapää Dahlqvist, also of Umeå University.

The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.

The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.

The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%). Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.

"The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor" in univariate but not multivariate analysis, they noted.

Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.

Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001). The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.

The findings show that first-degree relatives can have detectable amounts of autoantibodies, but may lack some other risk factors (such as SE or smoking) and still remain healthy. Another possibility is that they have particular as-yet-unidentified protective factors, the investigators said, adding that a follow-up study would be useful to help determine which of the isotypes provides the most information about disease progression and would thus be most important to analyze to help identify relatives likely to be affected by RA.

The investigators said they had no relevant financial disclosures.

Updated World Health Organization estimates are showing a downward trend in the incidence of gout in North America among 65-year-olds, but men in that age group on the continent are far more likely to suffer from gout than are men in Africa.

That’s a sampling of the updated data on a host of musculoskeletal disorders worldwide, including rheumatoid arthritis, said Dr. Lyn March at the Annual European Congress of Rheumatology.

She presented a preliminary report from the Musculoskeletal Expert Group that’s part of the new Global Burden of Diseases, Injuries, and Risk Factors Study, which began in the spring of 2007. This is the first major effort since the original Global Burden of Disease in 1990 study to carry out a complete systematic assessment of the data on all diseases and injuries, and to produce comprehensive and comparable estimates of the burden of diseases, injuries, and risk factors for two time periods (1990 and 2005), according to the WHO. The project is due to produce final estimates in the spring, said Dr. March of the Royal North Shore Hospital in Sydney.

Dr. March said the specific aims for the Musculoskeletal Expert Group are to include more population-based self-report data; to develop health-state descriptions for different levels of severity of osteoarthritis, rheumatoid arthritis, back pain, neck pain, gout, and other musculoskeletal disorders; and to update systematic literature reviews of incidence, prevalence, and mortality risk for these conditions. The group will also evaluate bone mineral density (g/cm²) as a risk factor for disability-adjusted life-year (DALY) burden, "which will put the [degenerative] bone condition on the map for policy making," she said.

"The methodology employed in the systematic review, development of lay health state descriptions, and generation of data estimates for calculating [DALYs] will be revealed," Dr. March said.

In 2000, the beginning of what the WHO declared "the Bone and Joint Decade," results from the previous Global Burden of Disease (GBD) study reported that rheumatoid arthritis accounted for 0.3% of global DALYs (a time-based measure that combined years of life lost to premature mortality and years of life lost to time lived in health states of less-than-ideal health). "These data enable, in part, an evaluation of the impact of the Bone and Joint Decade and the setting of the research agenda for the next decade," Dr. March said.

The GBD study investigated the incidence of 109 diseases and injuries and 10 risk factors across eight World Bank regions. In 2000, the WHO reported that osteoarthritis accounted for 1.1% of global DALYs, ranking 19th among all diseases and disorders, and rheumatoid arthritis accounted for 0.3% of DALYs. All musculoskeletal disorders combined had a prevalence of 2.1% of the worldwide population and ranked 12th in DALYs among all disorders, according to Dr. March. Preliminary data from the 2005 study show trends toward increases in the prevalence of osteoarthritis of the knee and hip, rheumatoid arthritis, and other musculoskeletal disease, and slight decreases in low-back pain and gout, she said, noting that the findings will likely have policy implications.

A 2005 update reported that musculoskeletal disorders are more common in developed countries.

Dr. March had no disclosures to report. The study received funding from the Bill and Melinda Gates Foundation and the Australian Commonwealth Government’s Department of Health and Aging.

Updated World Health Organization estimates are showing a downward trend in the incidence of gout in North America among 65-year-olds, but men in that age group on the continent are far more likely to suffer from gout than are men in Africa.

That’s a sampling of the updated data on a host of musculoskeletal disorders worldwide, including rheumatoid arthritis, said Dr. Lyn March at the Annual European Congress of Rheumatology.

She presented a preliminary report from the Musculoskeletal Expert Group that’s part of the new Global Burden of Diseases, Injuries, and Risk Factors Study, which began in the spring of 2007. This is the first major effort since the original Global Burden of Disease in 1990 study to carry out a complete systematic assessment of the data on all diseases and injuries, and to produce comprehensive and comparable estimates of the burden of diseases, injuries, and risk factors for two time periods (1990 and 2005), according to the WHO. The project is due to produce final estimates in the spring, said Dr. March of the Royal North Shore Hospital in Sydney.

Dr. March said the specific aims for the Musculoskeletal Expert Group are to include more population-based self-report data; to develop health-state descriptions for different levels of severity of osteoarthritis, rheumatoid arthritis, back pain, neck pain, gout, and other musculoskeletal disorders; and to update systematic literature reviews of incidence, prevalence, and mortality risk for these conditions. The group will also evaluate bone mineral density (g/cm²) as a risk factor for disability-adjusted life-year (DALY) burden, "which will put the [degenerative] bone condition on the map for policy making," she said.

"The methodology employed in the systematic review, development of lay health state descriptions, and generation of data estimates for calculating [DALYs] will be revealed," Dr. March said.

In 2000, the beginning of what the WHO declared "the Bone and Joint Decade," results from the previous Global Burden of Disease (GBD) study reported that rheumatoid arthritis accounted for 0.3% of global DALYs (a time-based measure that combined years of life lost to premature mortality and years of life lost to time lived in health states of less-than-ideal health). "These data enable, in part, an evaluation of the impact of the Bone and Joint Decade and the setting of the research agenda for the next decade," Dr. March said.

The GBD study investigated the incidence of 109 diseases and injuries and 10 risk factors across eight World Bank regions. In 2000, the WHO reported that osteoarthritis accounted for 1.1% of global DALYs, ranking 19th among all diseases and disorders, and rheumatoid arthritis accounted for 0.3% of DALYs. All musculoskeletal disorders combined had a prevalence of 2.1% of the worldwide population and ranked 12th in DALYs among all disorders, according to Dr. March. Preliminary data from the 2005 study show trends toward increases in the prevalence of osteoarthritis of the knee and hip, rheumatoid arthritis, and other musculoskeletal disease, and slight decreases in low-back pain and gout, she said, noting that the findings will likely have policy implications.

A 2005 update reported that musculoskeletal disorders are more common in developed countries.

Dr. March had no disclosures to report. The study received funding from the Bill and Melinda Gates Foundation and the Australian Commonwealth Government’s Department of Health and Aging.

Updated World Health Organization estimates are showing a downward trend in the incidence of gout in North America among 65-year-olds, but men in that age group on the continent are far more likely to suffer from gout than are men in Africa.

That’s a sampling of the updated data on a host of musculoskeletal disorders worldwide, including rheumatoid arthritis, said Dr. Lyn March at the Annual European Congress of Rheumatology.

She presented a preliminary report from the Musculoskeletal Expert Group that’s part of the new Global Burden of Diseases, Injuries, and Risk Factors Study, which began in the spring of 2007. This is the first major effort since the original Global Burden of Disease in 1990 study to carry out a complete systematic assessment of the data on all diseases and injuries, and to produce comprehensive and comparable estimates of the burden of diseases, injuries, and risk factors for two time periods (1990 and 2005), according to the WHO. The project is due to produce final estimates in the spring, said Dr. March of the Royal North Shore Hospital in Sydney.

Dr. March said the specific aims for the Musculoskeletal Expert Group are to include more population-based self-report data; to develop health-state descriptions for different levels of severity of osteoarthritis, rheumatoid arthritis, back pain, neck pain, gout, and other musculoskeletal disorders; and to update systematic literature reviews of incidence, prevalence, and mortality risk for these conditions. The group will also evaluate bone mineral density (g/cm²) as a risk factor for disability-adjusted life-year (DALY) burden, "which will put the [degenerative] bone condition on the map for policy making," she said.

"The methodology employed in the systematic review, development of lay health state descriptions, and generation of data estimates for calculating [DALYs] will be revealed," Dr. March said.

In 2000, the beginning of what the WHO declared "the Bone and Joint Decade," results from the previous Global Burden of Disease (GBD) study reported that rheumatoid arthritis accounted for 0.3% of global DALYs (a time-based measure that combined years of life lost to premature mortality and years of life lost to time lived in health states of less-than-ideal health). "These data enable, in part, an evaluation of the impact of the Bone and Joint Decade and the setting of the research agenda for the next decade," Dr. March said.

The GBD study investigated the incidence of 109 diseases and injuries and 10 risk factors across eight World Bank regions. In 2000, the WHO reported that osteoarthritis accounted for 1.1% of global DALYs, ranking 19th among all diseases and disorders, and rheumatoid arthritis accounted for 0.3% of DALYs. All musculoskeletal disorders combined had a prevalence of 2.1% of the worldwide population and ranked 12th in DALYs among all disorders, according to Dr. March. Preliminary data from the 2005 study show trends toward increases in the prevalence of osteoarthritis of the knee and hip, rheumatoid arthritis, and other musculoskeletal disease, and slight decreases in low-back pain and gout, she said, noting that the findings will likely have policy implications.

A 2005 update reported that musculoskeletal disorders are more common in developed countries.

Dr. March had no disclosures to report. The study received funding from the Bill and Melinda Gates Foundation and the Australian Commonwealth Government’s Department of Health and Aging.

Recent laboratory findings from Australia have shown a strong correlation between gum disease and worsening signs and symptoms of rheumatoid arthritis, one of the lead investigators reported May 25.

During his presentation at the annual European Congress of Rheumatology, Mark Bartold, Ph.D., who is a periodontist and the director of the Colgate Dental Research Centre at the University of Adelaide (South Australia), discussed his group’s recently published study of laboratory mice with preexisting periodontitis and worsening RA. "Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and rheumatoid arthritis," Dr. Bartold said in an interview.

The experiments showed that mice with coexisting periodontitis and RA exhibited more severe joint inflammation than did the mice with just RA, he said. Also, mice with both periodontitis and RA were more likely to demonstrate signs of arthritis in their rear paws, compared with mice with arthritis only. The progress of RA in mice with both conditions followed a more rapid course than it did in mice with just RA or just periodontitis, he reported.

Gum disease and RA could be related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of the dysfunction remains unknown, but recent scientific studies have suggested a link between the two, he said.

Although this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to have significant periodontal problems, compared with their nonrheumatoid counterparts. Likewise, people with severe gingivitis are more likely to have severe RA. Data from earlier studies have shown that individuals with RA had a 3.6-fold greater risk of moderate to severe periodontitis, and those with gum disease had a 2.2-fold greater risk of RA than did the general population.

Other studies have demonstrated that OPG (osteoprotegerin) and RANKL (receptor-activated nuclear factor–kappaB ligand) are highly expressed in both RA synovium and periodontitis lesions. Dr. Bartold noted pilot studies that have confirmed the potential to identify periodontal pathogen DNA in synovial tissues and inflamed human periodontal tissues. "It remains to be established whether treatment of periodontal disease and reduction of periodontal inflammation in patients with chronic rheumatoid arthritis will reduce the disease activity of rheumatoid arthritis," Dr. Bartold said.

Dr. Bartold’s research suggests that periodontitis and rheumatoid arthritis share a common development pathway within the RANK/RANKL/OPG axis, where a drop in OPG leads to reduced vascular protection. "Increases in RANKL levels within inflamed tissues may result in not only the development of vascular damage, but also activation of osteoclasts and subsequent bone resorption," he said.

The role of bacteria in arthritis has also garnered considerable attention, noted Dr. Bartold. Animal studies have demonstrated that arthritis can develop in response to different stimuli and through different effector pathways, including exogenous infections or microbial antigens. "If these observations are also applicable to human rheumatoid arthritis, we might expect that different types of infections – as well as other environmental exposures with the capacity to induce excessive proinflammatory cytokines in genetically susceptible individuals – may contribute to disease," he said.

Among the pathogens that have been implicated in rheumatoid arthritis patients are periodontopathic bacteria including Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, Bacteroides forsythus, and Aggregatibacter actinomycetemcomitans. Elevated antibodies to B. forsythus and P. intermedia have also been found in synovial fluid, he added.

The ultimate goal of emerging research is to determine whether the reduction of periodontal inflammation improves the disease activity of RA, he said. The clinical implications of these findings are that early intervention strategies to aid in the overall management of rheumatoid arthritis could include a periodontal assessment.

Dr. Bartold disclosed that he receives research support from the National Health and Medical Research Council of Australia, and acts as a consultant for Colgate and Nobel Biocare.

Recent laboratory findings from Australia have shown a strong correlation between gum disease and worsening signs and symptoms of rheumatoid arthritis, one of the lead investigators reported May 25.

During his presentation at the annual European Congress of Rheumatology, Mark Bartold, Ph.D., who is a periodontist and the director of the Colgate Dental Research Centre at the University of Adelaide (South Australia), discussed his group’s recently published study of laboratory mice with preexisting periodontitis and worsening RA. "Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and rheumatoid arthritis," Dr. Bartold said in an interview.

The experiments showed that mice with coexisting periodontitis and RA exhibited more severe joint inflammation than did the mice with just RA, he said. Also, mice with both periodontitis and RA were more likely to demonstrate signs of arthritis in their rear paws, compared with mice with arthritis only. The progress of RA in mice with both conditions followed a more rapid course than it did in mice with just RA or just periodontitis, he reported.

Gum disease and RA could be related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of the dysfunction remains unknown, but recent scientific studies have suggested a link between the two, he said.

Although this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to have significant periodontal problems, compared with their nonrheumatoid counterparts. Likewise, people with severe gingivitis are more likely to have severe RA. Data from earlier studies have shown that individuals with RA had a 3.6-fold greater risk of moderate to severe periodontitis, and those with gum disease had a 2.2-fold greater risk of RA than did the general population.

Other studies have demonstrated that OPG (osteoprotegerin) and RANKL (receptor-activated nuclear factor–kappaB ligand) are highly expressed in both RA synovium and periodontitis lesions. Dr. Bartold noted pilot studies that have confirmed the potential to identify periodontal pathogen DNA in synovial tissues and inflamed human periodontal tissues. "It remains to be established whether treatment of periodontal disease and reduction of periodontal inflammation in patients with chronic rheumatoid arthritis will reduce the disease activity of rheumatoid arthritis," Dr. Bartold said.

Dr. Bartold’s research suggests that periodontitis and rheumatoid arthritis share a common development pathway within the RANK/RANKL/OPG axis, where a drop in OPG leads to reduced vascular protection. "Increases in RANKL levels within inflamed tissues may result in not only the development of vascular damage, but also activation of osteoclasts and subsequent bone resorption," he said.

The role of bacteria in arthritis has also garnered considerable attention, noted Dr. Bartold. Animal studies have demonstrated that arthritis can develop in response to different stimuli and through different effector pathways, including exogenous infections or microbial antigens. "If these observations are also applicable to human rheumatoid arthritis, we might expect that different types of infections – as well as other environmental exposures with the capacity to induce excessive proinflammatory cytokines in genetically susceptible individuals – may contribute to disease," he said.

Among the pathogens that have been implicated in rheumatoid arthritis patients are periodontopathic bacteria including Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, Bacteroides forsythus, and Aggregatibacter actinomycetemcomitans. Elevated antibodies to B. forsythus and P. intermedia have also been found in synovial fluid, he added.

The ultimate goal of emerging research is to determine whether the reduction of periodontal inflammation improves the disease activity of RA, he said. The clinical implications of these findings are that early intervention strategies to aid in the overall management of rheumatoid arthritis could include a periodontal assessment.

Dr. Bartold disclosed that he receives research support from the National Health and Medical Research Council of Australia, and acts as a consultant for Colgate and Nobel Biocare.

Recent laboratory findings from Australia have shown a strong correlation between gum disease and worsening signs and symptoms of rheumatoid arthritis, one of the lead investigators reported May 25.

During his presentation at the annual European Congress of Rheumatology, Mark Bartold, Ph.D., who is a periodontist and the director of the Colgate Dental Research Centre at the University of Adelaide (South Australia), discussed his group’s recently published study of laboratory mice with preexisting periodontitis and worsening RA. "Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and rheumatoid arthritis," Dr. Bartold said in an interview.

The experiments showed that mice with coexisting periodontitis and RA exhibited more severe joint inflammation than did the mice with just RA, he said. Also, mice with both periodontitis and RA were more likely to demonstrate signs of arthritis in their rear paws, compared with mice with arthritis only. The progress of RA in mice with both conditions followed a more rapid course than it did in mice with just RA or just periodontitis, he reported.

Gum disease and RA could be related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of the dysfunction remains unknown, but recent scientific studies have suggested a link between the two, he said.

Although this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to have significant periodontal problems, compared with their nonrheumatoid counterparts. Likewise, people with severe gingivitis are more likely to have severe RA. Data from earlier studies have shown that individuals with RA had a 3.6-fold greater risk of moderate to severe periodontitis, and those with gum disease had a 2.2-fold greater risk of RA than did the general population.

Other studies have demonstrated that OPG (osteoprotegerin) and RANKL (receptor-activated nuclear factor–kappaB ligand) are highly expressed in both RA synovium and periodontitis lesions. Dr. Bartold noted pilot studies that have confirmed the potential to identify periodontal pathogen DNA in synovial tissues and inflamed human periodontal tissues. "It remains to be established whether treatment of periodontal disease and reduction of periodontal inflammation in patients with chronic rheumatoid arthritis will reduce the disease activity of rheumatoid arthritis," Dr. Bartold said.

Dr. Bartold’s research suggests that periodontitis and rheumatoid arthritis share a common development pathway within the RANK/RANKL/OPG axis, where a drop in OPG leads to reduced vascular protection. "Increases in RANKL levels within inflamed tissues may result in not only the development of vascular damage, but also activation of osteoclasts and subsequent bone resorption," he said.

The role of bacteria in arthritis has also garnered considerable attention, noted Dr. Bartold. Animal studies have demonstrated that arthritis can develop in response to different stimuli and through different effector pathways, including exogenous infections or microbial antigens. "If these observations are also applicable to human rheumatoid arthritis, we might expect that different types of infections – as well as other environmental exposures with the capacity to induce excessive proinflammatory cytokines in genetically susceptible individuals – may contribute to disease," he said.

Among the pathogens that have been implicated in rheumatoid arthritis patients are periodontopathic bacteria including Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, Bacteroides forsythus, and Aggregatibacter actinomycetemcomitans. Elevated antibodies to B. forsythus and P. intermedia have also been found in synovial fluid, he added.

The ultimate goal of emerging research is to determine whether the reduction of periodontal inflammation improves the disease activity of RA, he said. The clinical implications of these findings are that early intervention strategies to aid in the overall management of rheumatoid arthritis could include a periodontal assessment.

Dr. Bartold disclosed that he receives research support from the National Health and Medical Research Council of Australia, and acts as a consultant for Colgate and Nobel Biocare.

The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

The use of tofacitinib in combination with conventional background disease-modifying antirheumatic drugs is associated with rapid, significant, and clinically meaningful reductions in signs and symptoms of rheumatoid arthritis, as well as with improvement in physical function, according to findings from a phase III study.

The data were presented by Dr. Joel M. Kremer at a press briefing during the annual meeting of the European Congress of Rheumatology.

"The very rapid responses were sustained beyond 6 months to 12 months," Dr. Kremer noted.

The findings from the 12-month, placebo-controlled study are consistent with those from phase II studies and a phase III monotherapy study of the novel oral JAK inhibitor, and no new safety signals were detected, said Dr. Kremer, a rheumatologist and the Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.

In 792 patients with inadequate response to nonbiologic background DMARDs – most often methotrexate – who were randomized to receive either 5 mg or 10 mg of tofacitinib or placebo twice daily, tofacitinib was statistically superior to placebo for all primary efficacy end points, including an ACR 20 response (that is, an American College of Rheumatology score based on a 20% improvement in specified parameters), a DAS28-4(ESR) response (that is, a disease activity score based on a 28-joint count and the erythrocyte sedimentation rate) of less than 2.6 at month 6, and a change in HAQ-DI (Health and Quality of Life–Disability Index) at month 3.

In the 5-mg, 10-mg, and placebo groups, respectively, ACR 20 responses at 6 months were 52.7%, 58.3%, and 31.2%; DAS28-4(ESR) responses of less than 2.6 at 6 months were 11.0%, 14.8% and 2.7%; and changes in HAQ-DI at 3 months were –0.46, –0.56, and –0.21.

Significant differences between the treatment and placebo groups were seen by week 2, Dr. Kremer noted.

The most common adverse events included infections and infestations, which were generally mild. However, four deaths and four opportunistic infections occurred. Deaths included one from acute heart failure and one from respiratory failure in the 10-mg treatment group, and one from traumatic brain injury and one from RA in the 5-mg treatment group, both following discontinuation of treatment (at 22 and 42 days, respectively). Serious infectious events (including opportunistic infections, such as TB, Cryptococcus, and herpes zoster) occurred in two patients in the 5-mg group and in four patients in the 10-mg group during months 0-4, and in one patient in each group during months 3-6. Other adverse events included decreases in neutrophils, increases in LDL and HDL cholesterol levels, small increases in serum creatinine, and anemia.

Patients in the study were mostly women (81.4%) with a mean age in the treatment and placebo groups, respectively, of 50.8 and 53.3 years at baseline, and a mean disease duration of 8.1 and 10.2 years. Nonresponders in the placebo group at month 3 were advanced to tofacitinib, and all remaining patients in the placebo group were advanced at 6 months.

"This large, phase III trial adds to the body of evidence on the efficacy of tofacitinib," Dr. Kremer concluded.

There were four deaths but only one was thought to be treatment related, Dr. Kremer noted. The patient’s spouse refused to grant permission for an autopsy, he added.

Dr. Kremer reported receiving grant and/or research support from Pfizer Inc. and serving as a consultant for Pfizer. Other study authors disclosed having similar relationships with Pfizer, as well as serving on the speakers bureau and/or being a shareholder or employee of Pfizer.

The use of tofacitinib in combination with conventional background disease-modifying antirheumatic drugs is associated with rapid, significant, and clinically meaningful reductions in signs and symptoms of rheumatoid arthritis, as well as with improvement in physical function, according to findings from a phase III study.

The data were presented by Dr. Joel M. Kremer at a press briefing during the annual meeting of the European Congress of Rheumatology.

"The very rapid responses were sustained beyond 6 months to 12 months," Dr. Kremer noted.

The findings from the 12-month, placebo-controlled study are consistent with those from phase II studies and a phase III monotherapy study of the novel oral JAK inhibitor, and no new safety signals were detected, said Dr. Kremer, a rheumatologist and the Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.

In 792 patients with inadequate response to nonbiologic background DMARDs – most often methotrexate – who were randomized to receive either 5 mg or 10 mg of tofacitinib or placebo twice daily, tofacitinib was statistically superior to placebo for all primary efficacy end points, including an ACR 20 response (that is, an American College of Rheumatology score based on a 20% improvement in specified parameters), a DAS28-4(ESR) response (that is, a disease activity score based on a 28-joint count and the erythrocyte sedimentation rate) of less than 2.6 at month 6, and a change in HAQ-DI (Health and Quality of Life–Disability Index) at month 3.

In the 5-mg, 10-mg, and placebo groups, respectively, ACR 20 responses at 6 months were 52.7%, 58.3%, and 31.2%; DAS28-4(ESR) responses of less than 2.6 at 6 months were 11.0%, 14.8% and 2.7%; and changes in HAQ-DI at 3 months were –0.46, –0.56, and –0.21.

Significant differences between the treatment and placebo groups were seen by week 2, Dr. Kremer noted.

The most common adverse events included infections and infestations, which were generally mild. However, four deaths and four opportunistic infections occurred. Deaths included one from acute heart failure and one from respiratory failure in the 10-mg treatment group, and one from traumatic brain injury and one from RA in the 5-mg treatment group, both following discontinuation of treatment (at 22 and 42 days, respectively). Serious infectious events (including opportunistic infections, such as TB, Cryptococcus, and herpes zoster) occurred in two patients in the 5-mg group and in four patients in the 10-mg group during months 0-4, and in one patient in each group during months 3-6. Other adverse events included decreases in neutrophils, increases in LDL and HDL cholesterol levels, small increases in serum creatinine, and anemia.

Patients in the study were mostly women (81.4%) with a mean age in the treatment and placebo groups, respectively, of 50.8 and 53.3 years at baseline, and a mean disease duration of 8.1 and 10.2 years. Nonresponders in the placebo group at month 3 were advanced to tofacitinib, and all remaining patients in the placebo group were advanced at 6 months.

"This large, phase III trial adds to the body of evidence on the efficacy of tofacitinib," Dr. Kremer concluded.

There were four deaths but only one was thought to be treatment related, Dr. Kremer noted. The patient’s spouse refused to grant permission for an autopsy, he added.

Dr. Kremer reported receiving grant and/or research support from Pfizer Inc. and serving as a consultant for Pfizer. Other study authors disclosed having similar relationships with Pfizer, as well as serving on the speakers bureau and/or being a shareholder or employee of Pfizer.

The use of tofacitinib in combination with conventional background disease-modifying antirheumatic drugs is associated with rapid, significant, and clinically meaningful reductions in signs and symptoms of rheumatoid arthritis, as well as with improvement in physical function, according to findings from a phase III study.

The data were presented by Dr. Joel M. Kremer at a press briefing during the annual meeting of the European Congress of Rheumatology.

"The very rapid responses were sustained beyond 6 months to 12 months," Dr. Kremer noted.

The findings from the 12-month, placebo-controlled study are consistent with those from phase II studies and a phase III monotherapy study of the novel oral JAK inhibitor, and no new safety signals were detected, said Dr. Kremer, a rheumatologist and the Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.

In 792 patients with inadequate response to nonbiologic background DMARDs – most often methotrexate – who were randomized to receive either 5 mg or 10 mg of tofacitinib or placebo twice daily, tofacitinib was statistically superior to placebo for all primary efficacy end points, including an ACR 20 response (that is, an American College of Rheumatology score based on a 20% improvement in specified parameters), a DAS28-4(ESR) response (that is, a disease activity score based on a 28-joint count and the erythrocyte sedimentation rate) of less than 2.6 at month 6, and a change in HAQ-DI (Health and Quality of Life–Disability Index) at month 3.

In the 5-mg, 10-mg, and placebo groups, respectively, ACR 20 responses at 6 months were 52.7%, 58.3%, and 31.2%; DAS28-4(ESR) responses of less than 2.6 at 6 months were 11.0%, 14.8% and 2.7%; and changes in HAQ-DI at 3 months were –0.46, –0.56, and –0.21.

Significant differences between the treatment and placebo groups were seen by week 2, Dr. Kremer noted.

The most common adverse events included infections and infestations, which were generally mild. However, four deaths and four opportunistic infections occurred. Deaths included one from acute heart failure and one from respiratory failure in the 10-mg treatment group, and one from traumatic brain injury and one from RA in the 5-mg treatment group, both following discontinuation of treatment (at 22 and 42 days, respectively). Serious infectious events (including opportunistic infections, such as TB, Cryptococcus, and herpes zoster) occurred in two patients in the 5-mg group and in four patients in the 10-mg group during months 0-4, and in one patient in each group during months 3-6. Other adverse events included decreases in neutrophils, increases in LDL and HDL cholesterol levels, small increases in serum creatinine, and anemia.

Patients in the study were mostly women (81.4%) with a mean age in the treatment and placebo groups, respectively, of 50.8 and 53.3 years at baseline, and a mean disease duration of 8.1 and 10.2 years. Nonresponders in the placebo group at month 3 were advanced to tofacitinib, and all remaining patients in the placebo group were advanced at 6 months.

"This large, phase III trial adds to the body of evidence on the efficacy of tofacitinib," Dr. Kremer concluded.

There were four deaths but only one was thought to be treatment related, Dr. Kremer noted. The patient’s spouse refused to grant permission for an autopsy, he added.

Dr. Kremer reported receiving grant and/or research support from Pfizer Inc. and serving as a consultant for Pfizer. Other study authors disclosed having similar relationships with Pfizer, as well as serving on the speakers bureau and/or being a shareholder or employee of Pfizer.

SAN FRANCISCO – What do individuals with rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease have in common?

They all have debilitating chronic diseases that throw off high levels of systemic inflammation. And what’s more, they share a newly recognized predisposition to atrial fibrillation compared with the general population, according to two studies presented at the annual meeting of the Heart Rhythm Society.

Dr. Prabhat Hebbar and his coworkers used the Nationwide Inpatient Sample database for 2008, which contains discharge diagnoses for roughly 1,000 U.S. hospitals in 40 states, to identify 86,497 patients with the diagnosis of atrial fibrillation (AF) and 100,000 randomly selected controls from the rest of the database.

The frequency of rheumatoid arthritis among patients with AF was 0.28%, compared with 0.13% in controls not having AF. The frequency of SLE in the AF population was 0.05%, compared with 0.12% in controls.

However, after adjusting for demographic factors – for example, patients with SLE were skewed considerably younger than were those with AF, and the AF group had significantly higher rates of comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease – the adjusted odds ratio for rheumatoid arthritis in patients with AF was 1.65. An identical odds ratio of 1.65 was found for SLE in AF patients, according to Dr. Hebbar of the University of Arkansas for Health Sciences, Little Rock.

The explanation for this association lies in the likely pathogenic role inflammation plays in AF. This inflammation can result from the physical handling of the heart during cardiac surgery, with the consequence of postoperative new-onset AF. Or the trigger can be the systemic inflammation that’s a key part of a chronic rheumatologic or gut disease.

This point was underscored by Dr. Deepak J. Pattanshetty in a separate retrospective cohort study. He and his coworkers reviewed the records of 142 patients with inflammatory bowel disease (IBD) at Metro Health Medical Center in Cleveland, and compared them with a large general population described in the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study of 1.89 million enrollees in Kaiser Permanente Northern California (JAMA 2001;285:2370-5).

The prevalence of AF in the IBD patients was 11%, compared with 0.95% in the Kaiser Permanente controls without IBD. This disparity is all the more striking given that the IBD patients were significantly younger, with a mean age of 57 years, compared with 71 years for controls.

Atrial fibrillation is the most common sustained arrhythmia. Its prevalence in the general population is strongly age-dependent, with a rate of less than 1.7% in individuals under age 65, rising to 4%-9% in 65- to 80-year-olds, and to 10% or more after age 80, noted Dr. Pattanshetty.

There were no significant differences between the IBD cohort and the controls in terms of hypertension, diabetes, and other conventional risk factors for AF. The explanation for the 11-fold increased prevalence of AF seen in patients with IBD probably is that recurrent flares of the gut disease are known to lead to increased systemic levels of C-reactive protein and inflammatory cytokines including interleukin-6. These could predispose to the atrial arrhythmia, said Dr. Pattanshetty.

The associations between AF and rheumatologic and gastrointestinal diseases not only provide insight into the pathogenesis of the arrhythmia, but also have a practical implication for patient care. Patients with these systemic diseases need to understand that they are at elevated risk for the arrhythmia, and that if they feel symptoms such as a rapid or irregular heart beat they should seek medical attention so that if they do have AF their stroke risk can be managed appropriately.

Dr. Hebbar and Dr. Pattanshetty declared having no financial conflicts of interest.

SAN FRANCISCO – What do individuals with rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease have in common?

They all have debilitating chronic diseases that throw off high levels of systemic inflammation. And what’s more, they share a newly recognized predisposition to atrial fibrillation compared with the general population, according to two studies presented at the annual meeting of the Heart Rhythm Society.

Dr. Prabhat Hebbar and his coworkers used the Nationwide Inpatient Sample database for 2008, which contains discharge diagnoses for roughly 1,000 U.S. hospitals in 40 states, to identify 86,497 patients with the diagnosis of atrial fibrillation (AF) and 100,000 randomly selected controls from the rest of the database.

The frequency of rheumatoid arthritis among patients with AF was 0.28%, compared with 0.13% in controls not having AF. The frequency of SLE in the AF population was 0.05%, compared with 0.12% in controls.

However, after adjusting for demographic factors – for example, patients with SLE were skewed considerably younger than were those with AF, and the AF group had significantly higher rates of comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease – the adjusted odds ratio for rheumatoid arthritis in patients with AF was 1.65. An identical odds ratio of 1.65 was found for SLE in AF patients, according to Dr. Hebbar of the University of Arkansas for Health Sciences, Little Rock.

The explanation for this association lies in the likely pathogenic role inflammation plays in AF. This inflammation can result from the physical handling of the heart during cardiac surgery, with the consequence of postoperative new-onset AF. Or the trigger can be the systemic inflammation that’s a key part of a chronic rheumatologic or gut disease.

This point was underscored by Dr. Deepak J. Pattanshetty in a separate retrospective cohort study. He and his coworkers reviewed the records of 142 patients with inflammatory bowel disease (IBD) at Metro Health Medical Center in Cleveland, and compared them with a large general population described in the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study of 1.89 million enrollees in Kaiser Permanente Northern California (JAMA 2001;285:2370-5).

The prevalence of AF in the IBD patients was 11%, compared with 0.95% in the Kaiser Permanente controls without IBD. This disparity is all the more striking given that the IBD patients were significantly younger, with a mean age of 57 years, compared with 71 years for controls.

Atrial fibrillation is the most common sustained arrhythmia. Its prevalence in the general population is strongly age-dependent, with a rate of less than 1.7% in individuals under age 65, rising to 4%-9% in 65- to 80-year-olds, and to 10% or more after age 80, noted Dr. Pattanshetty.

There were no significant differences between the IBD cohort and the controls in terms of hypertension, diabetes, and other conventional risk factors for AF. The explanation for the 11-fold increased prevalence of AF seen in patients with IBD probably is that recurrent flares of the gut disease are known to lead to increased systemic levels of C-reactive protein and inflammatory cytokines including interleukin-6. These could predispose to the atrial arrhythmia, said Dr. Pattanshetty.

The associations between AF and rheumatologic and gastrointestinal diseases not only provide insight into the pathogenesis of the arrhythmia, but also have a practical implication for patient care. Patients with these systemic diseases need to understand that they are at elevated risk for the arrhythmia, and that if they feel symptoms such as a rapid or irregular heart beat they should seek medical attention so that if they do have AF their stroke risk can be managed appropriately.

Dr. Hebbar and Dr. Pattanshetty declared having no financial conflicts of interest.

SAN FRANCISCO – What do individuals with rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease have in common?

They all have debilitating chronic diseases that throw off high levels of systemic inflammation. And what’s more, they share a newly recognized predisposition to atrial fibrillation compared with the general population, according to two studies presented at the annual meeting of the Heart Rhythm Society.

Dr. Prabhat Hebbar and his coworkers used the Nationwide Inpatient Sample database for 2008, which contains discharge diagnoses for roughly 1,000 U.S. hospitals in 40 states, to identify 86,497 patients with the diagnosis of atrial fibrillation (AF) and 100,000 randomly selected controls from the rest of the database.

The frequency of rheumatoid arthritis among patients with AF was 0.28%, compared with 0.13% in controls not having AF. The frequency of SLE in the AF population was 0.05%, compared with 0.12% in controls.

However, after adjusting for demographic factors – for example, patients with SLE were skewed considerably younger than were those with AF, and the AF group had significantly higher rates of comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease – the adjusted odds ratio for rheumatoid arthritis in patients with AF was 1.65. An identical odds ratio of 1.65 was found for SLE in AF patients, according to Dr. Hebbar of the University of Arkansas for Health Sciences, Little Rock.

The explanation for this association lies in the likely pathogenic role inflammation plays in AF. This inflammation can result from the physical handling of the heart during cardiac surgery, with the consequence of postoperative new-onset AF. Or the trigger can be the systemic inflammation that’s a key part of a chronic rheumatologic or gut disease.

This point was underscored by Dr. Deepak J. Pattanshetty in a separate retrospective cohort study. He and his coworkers reviewed the records of 142 patients with inflammatory bowel disease (IBD) at Metro Health Medical Center in Cleveland, and compared them with a large general population described in the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study of 1.89 million enrollees in Kaiser Permanente Northern California (JAMA 2001;285:2370-5).

The prevalence of AF in the IBD patients was 11%, compared with 0.95% in the Kaiser Permanente controls without IBD. This disparity is all the more striking given that the IBD patients were significantly younger, with a mean age of 57 years, compared with 71 years for controls.

Atrial fibrillation is the most common sustained arrhythmia. Its prevalence in the general population is strongly age-dependent, with a rate of less than 1.7% in individuals under age 65, rising to 4%-9% in 65- to 80-year-olds, and to 10% or more after age 80, noted Dr. Pattanshetty.

There were no significant differences between the IBD cohort and the controls in terms of hypertension, diabetes, and other conventional risk factors for AF. The explanation for the 11-fold increased prevalence of AF seen in patients with IBD probably is that recurrent flares of the gut disease are known to lead to increased systemic levels of C-reactive protein and inflammatory cytokines including interleukin-6. These could predispose to the atrial arrhythmia, said Dr. Pattanshetty.

The associations between AF and rheumatologic and gastrointestinal diseases not only provide insight into the pathogenesis of the arrhythmia, but also have a practical implication for patient care. Patients with these systemic diseases need to understand that they are at elevated risk for the arrhythmia, and that if they feel symptoms such as a rapid or irregular heart beat they should seek medical attention so that if they do have AF their stroke risk can be managed appropriately.

Dr. Hebbar and Dr. Pattanshetty declared having no financial conflicts of interest.