Sharon Worcester

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

“On a gluten-free diet, the child's headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues,” Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patient can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don't respond to treatment. These are the patients with whom “you just don't know what to do,” she said, adding that these are the patients who don't clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

Systemic Link Needs Further Study

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be “taken with a grain of salt,” she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252–5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren's syndrome.

A 2003 report said Sjögren's syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren's syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613–9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison's disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

“On a gluten-free diet, the child's headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues,” Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patient can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don't respond to treatment. These are the patients with whom “you just don't know what to do,” she said, adding that these are the patients who don't clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

Systemic Link Needs Further Study

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be “taken with a grain of salt,” she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252–5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren's syndrome.

A 2003 report said Sjögren's syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren's syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613–9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison's disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

“On a gluten-free diet, the child's headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues,” Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patient can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don't respond to treatment. These are the patients with whom “you just don't know what to do,” she said, adding that these are the patients who don't clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

Systemic Link Needs Further Study

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be “taken with a grain of salt,” she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252–5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren's syndrome.

A 2003 report said Sjögren's syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren's syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613–9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison's disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

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 Dr. Samuel Whittle.

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 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.

▸ 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 aren't 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 Abbott. Neither Dr. Whittle nor any co-authors on this study had additional disclosures to report.

To watch an interview with Dr. Whittlew, scan this QR code with a smartphone.

Dr. Samuel Whittle discussed the proposed 3e recommendations with senior reporter Heidi Splete.

Source Heidi Splete/Elsevier Global Medical News

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 Dr. Samuel Whittle.

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 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.

▸ 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 aren't 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 Abbott. Neither Dr. Whittle nor any co-authors on this study had additional disclosures to report.

To watch an interview with Dr. Whittlew, scan this QR code with a smartphone.

Dr. Samuel Whittle discussed the proposed 3e recommendations with senior reporter Heidi Splete.

Source Heidi Splete/Elsevier Global Medical News

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 Dr. Samuel Whittle.

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 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.

▸ 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 aren't 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 Abbott. Neither Dr. Whittle nor any co-authors on this study had additional disclosures to report.

To watch an interview with Dr. Whittlew, scan this QR code with a smartphone.

Dr. Samuel Whittle discussed the proposed 3e recommendations with senior reporter Heidi Splete.

Source Heidi Splete/Elsevier Global Medical News

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 meeting, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå University, the scheduled presenter who was unable to attend.

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 Rantapåå 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 investigators said they had no relevant financial disclosures.

Both RA patients and their relatives have higher rates of carriage of certain genetic biomarkers than do controls.

Source © Suprijono Suharjoto/Fotolia.com

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 meeting, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå University, the scheduled presenter who was unable to attend.

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 Rantapåå 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 investigators said they had no relevant financial disclosures.

Both RA patients and their relatives have higher rates of carriage of certain genetic biomarkers than do controls.

Source © Suprijono Suharjoto/Fotolia.com

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 meeting, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå University, the scheduled presenter who was unable to attend.

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 Rantapåå 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 investigators said they had no relevant financial disclosures.

Both RA patients and their relatives have higher rates of carriage of certain genetic biomarkers than do controls.

Source © Suprijono Suharjoto/Fotolia.com

It may be appropriate to forgo dual-energy x-ray absorptiometry scanning and instead use body mass index to rule out osteoporosis in some obese patients, according to the findings of a large study presented by Dr. Thomas Nelson at the annual European Congress of Rheumatology.

Patients in the study with a BMI greater than 30 kg/m², age younger than 70 years, and few clinical risk factors for osteoporosis had a low prevalence of osteoporosis, compared with the general population, said Dr. Nelson, a rheumatologist at the Royal Lancaster (England) Infirmary.

For example, after correction for risk factors including age, sex, index of deprivation, and a number of clinical risk factors (such as recurrent falls, smoking, rheumatoid arthritis, corticosteroid use, maternal hip fracture, excessive consumption of alcohol, fragility fractures, and secondary osteoporosis), a low BMI in 10,657 patients who were randomly assigned to a reference cohort was found to be an independent predictor of osteoporosis (area under the ROC curve, 0.72 for total hip osteoporosis and 0.67 for lumbar spine osteoporosis).

Use of a BMI threshold "of approximately 30 was found to give 93.6% sensitivity for hip osteoporosis and 90.8% for lumbar spine osteoporosis," Dr. Nelson said.

Thus, a hypothesis was formed that in obese patients, osteoporosis could be excluded without dual-energy x-ray absorptiometry (DXA), and only 6.4% of patients with hip osteoporosis – and 9.2% with lumbar spine osteoporosis – would be missed.

When the hypothesis was applied in a validation cohort of 5,329 patients, hip osteoporosis was seen in 2.7% of obese patients, and lumbar spine osteoporosis was observed in 7.2%, compared with 10.7% and 16.6%, respectively, in the entire cohort.

Among those younger than age 70 years, only 0.7% and 5.4% had hip and lumbar spine osteoporosis, respectively.

Patients in the study were scanned between June 2004 and August 2010. They were randomly assigned to the reference or validation cohorts. The cohorts did not differ in regard to age, sex, BMI, body fat percentage, deprivation, or number of clinical risk factors. About 23% of patients in both groups were obese.

Should the suggestion that DXA scanning is unnecessary for ruling out osteoporosis in obese patients be validated in other populations, the finding could help to minimize radiation exposure, improve convenience, and lower costs for many patients. However, it is plausible that a greater bone mineral density is required by obese patients, compared with nonobese patients, to avoid symptoms and fracture risk associated with osteoporosis, and further research is required in this area, he concluded.

Dr. Nelson had no disclosures to report.

It may be appropriate to forgo dual-energy x-ray absorptiometry scanning and instead use body mass index to rule out osteoporosis in some obese patients, according to the findings of a large study presented by Dr. Thomas Nelson at the annual European Congress of Rheumatology.

Patients in the study with a BMI greater than 30 kg/m², age younger than 70 years, and few clinical risk factors for osteoporosis had a low prevalence of osteoporosis, compared with the general population, said Dr. Nelson, a rheumatologist at the Royal Lancaster (England) Infirmary.

For example, after correction for risk factors including age, sex, index of deprivation, and a number of clinical risk factors (such as recurrent falls, smoking, rheumatoid arthritis, corticosteroid use, maternal hip fracture, excessive consumption of alcohol, fragility fractures, and secondary osteoporosis), a low BMI in 10,657 patients who were randomly assigned to a reference cohort was found to be an independent predictor of osteoporosis (area under the ROC curve, 0.72 for total hip osteoporosis and 0.67 for lumbar spine osteoporosis).

Use of a BMI threshold "of approximately 30 was found to give 93.6% sensitivity for hip osteoporosis and 90.8% for lumbar spine osteoporosis," Dr. Nelson said.

Thus, a hypothesis was formed that in obese patients, osteoporosis could be excluded without dual-energy x-ray absorptiometry (DXA), and only 6.4% of patients with hip osteoporosis – and 9.2% with lumbar spine osteoporosis – would be missed.

When the hypothesis was applied in a validation cohort of 5,329 patients, hip osteoporosis was seen in 2.7% of obese patients, and lumbar spine osteoporosis was observed in 7.2%, compared with 10.7% and 16.6%, respectively, in the entire cohort.

Among those younger than age 70 years, only 0.7% and 5.4% had hip and lumbar spine osteoporosis, respectively.

Patients in the study were scanned between June 2004 and August 2010. They were randomly assigned to the reference or validation cohorts. The cohorts did not differ in regard to age, sex, BMI, body fat percentage, deprivation, or number of clinical risk factors. About 23% of patients in both groups were obese.

Should the suggestion that DXA scanning is unnecessary for ruling out osteoporosis in obese patients be validated in other populations, the finding could help to minimize radiation exposure, improve convenience, and lower costs for many patients. However, it is plausible that a greater bone mineral density is required by obese patients, compared with nonobese patients, to avoid symptoms and fracture risk associated with osteoporosis, and further research is required in this area, he concluded.

Dr. Nelson had no disclosures to report.

It may be appropriate to forgo dual-energy x-ray absorptiometry scanning and instead use body mass index to rule out osteoporosis in some obese patients, according to the findings of a large study presented by Dr. Thomas Nelson at the annual European Congress of Rheumatology.

Patients in the study with a BMI greater than 30 kg/m², age younger than 70 years, and few clinical risk factors for osteoporosis had a low prevalence of osteoporosis, compared with the general population, said Dr. Nelson, a rheumatologist at the Royal Lancaster (England) Infirmary.

For example, after correction for risk factors including age, sex, index of deprivation, and a number of clinical risk factors (such as recurrent falls, smoking, rheumatoid arthritis, corticosteroid use, maternal hip fracture, excessive consumption of alcohol, fragility fractures, and secondary osteoporosis), a low BMI in 10,657 patients who were randomly assigned to a reference cohort was found to be an independent predictor of osteoporosis (area under the ROC curve, 0.72 for total hip osteoporosis and 0.67 for lumbar spine osteoporosis).

Use of a BMI threshold "of approximately 30 was found to give 93.6% sensitivity for hip osteoporosis and 90.8% for lumbar spine osteoporosis," Dr. Nelson said.

Thus, a hypothesis was formed that in obese patients, osteoporosis could be excluded without dual-energy x-ray absorptiometry (DXA), and only 6.4% of patients with hip osteoporosis – and 9.2% with lumbar spine osteoporosis – would be missed.

When the hypothesis was applied in a validation cohort of 5,329 patients, hip osteoporosis was seen in 2.7% of obese patients, and lumbar spine osteoporosis was observed in 7.2%, compared with 10.7% and 16.6%, respectively, in the entire cohort.

Among those younger than age 70 years, only 0.7% and 5.4% had hip and lumbar spine osteoporosis, respectively.

Patients in the study were scanned between June 2004 and August 2010. They were randomly assigned to the reference or validation cohorts. The cohorts did not differ in regard to age, sex, BMI, body fat percentage, deprivation, or number of clinical risk factors. About 23% of patients in both groups were obese.

Should the suggestion that DXA scanning is unnecessary for ruling out osteoporosis in obese patients be validated in other populations, the finding could help to minimize radiation exposure, improve convenience, and lower costs for many patients. However, it is plausible that a greater bone mineral density is required by obese patients, compared with nonobese patients, to avoid symptoms and fracture risk associated with osteoporosis, and further research is required in this area, he concluded.

Dr. Nelson had no 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.

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.

 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.

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.

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.

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.