Rheumatoid Arthritis

NEW ORLEANS – Induction or exacerbation of psoriasis is a common and paradoxical side effect of anti–tumor necrosis factor-alpha therapy for rheumatologic and inflammatory bowel diseases.

The paradox lies in the fact that anti-TNF agents are a tremendously effective therapy for moderate to severe psoriasis.

So when a patient with Crohn's disease or rheumatoid arthritis in remission induced by anti-TNF therapy suddenly develops severe psoriasis, it creates a clinical conundrum, observed Dr. Brian F. Mandell at the meeting Dr. Mandell is a rheumatologist who is professor and chairman of the department of medicine at the Cleveland Clinic.

Dr. Alice Gottlieb noted that psoriasis induced by TNF blockers is a class effect that, although rare, can be severe and debilitating, especially in cases of palmar-plantar psoriasis.

Unfortunately, palmar-plantar psoriasis is much more common in TNF-blocker-induced/flared psoriasis than it is in the general psoriasis population, Dr. Gottlieb said in an interview.

In his report, Dr. Mandell noted that a strikingly unusual feature of this cutaneous drug reaction is how long it takes to appear. In a recent study by European gastroenterologists and dermatologists, the median interval between the start of infliximab (Remicade) for inflammatory bowel disease (IBD) and the occurrence of psoriasis was 17 months; for adalimumab (Humira), the median interval was 12 months; and with certolizumab (Cimzia), it was 4.5 months, noted Dr. Mandell.

The European study involved 85 patients being treated with anti-TNF agents for Crohn's disease or ulcerative colitis who developed severe skin lesions while their IBD remained quiescent.

Sixty-two patients developed dermatologist-diagnosed psoriasis marked by the classic histologic features, including epidermal hyperplasia, parakeratosis, agranulosis, elongated rete ridges, and dilated dermal capillaries.

Fourteen patients had a history of psoriasis prior to anti-TNF therapy, and another 8 had a family history of the skin disease.

The most frequently affected site was the scalp, in 40 patients. A total of 27 patients had involvement at the axillae, groin, and other flexural sites, which are not typical locations for psoriasis; 21 had both scalp and flexural lesions; and 22 had palmar-plantar psoriasis.

Dr. Mandell's data shed some light on treatments: All 62 patients were promptly placed on topical therapy with corticosteroids, vitamin D analogs, keratolytics, and emollients, with phototherapy being prescribed in selected cases.

Twenty-five patients showed a favorable response, while the remaining 37 had no response at all to topical therapy.

Eighteen patients discontinued anti-TNF therapy altogether, of whom 16 experienced complete regression of their psoriasis. Twenty-six patients switched to a second TNF inhibitor; only 1 showed improvement in skin lesions.

Ten of the 23 patients who developed eczematous lesions had a history of atopy. The median duration of anti-TNF therapy prior to onset of the skin lesions was 11 months for infliximab, 6 months for adalimumab, and 14 months for certolizumab.

The histology was consistent with eczema. The lesions were equally distributed on the scalp, flexural areas, trunk, face, and limbs. Sixteen of 23 patients had a favorable response to topical steroids and emollients. Five patients were switched to a second anti-TNF biologic, but only one experienced resultant skin improvement. Four patients were eventually taken off anti-TNF therapy altogether, with complete clearing of skin lesions in a median of 3 months.

Dr. Gottlieb, chair of dermatology at the Tufts Medical Center, Boston, noted that the best clinical results are obtained when the TNF blocker is discontinued. Often systemic immunosuppression/immunomodulation is required to control psoriasis induced by a TNF blocker (J. Dermatolog. Treat. 2009;20:100-8).

Altogether, recurrent severe skin lesions caused one-third of IBD patients in this study to discontinue anti-TNF therapy. Extrapolating from the broader Lille University gastroenterology experience, the French investigators estimated that patients on anti-TNF therapy have roughly a 5% risk of developing inflammatory skin lesions, and that the need to halt biologic therapy due to an inability to gain control of the skin eruption is around 1% (Clin. Gastroenterol. Hepatol. 2010;8:1048-55).

Dr. Mandell said the European report on anti-TNF-treated IBD patients accurately reflects his own experience in using the biologics for rheumatoid arthritis, although he's had more success than the gastroenterologists in switching patients to a different agent within the anti-TNF class in order to continue with treatment.

But he noted that it's necessary to discontinue anti-TNF therapy altogether in a minority of Rheumatology patients, and even then the psoriasiform reactions don't always resolve.

Dr. Mandell said he had no relevant commercial interests. Dr. Gottlieb declared financial relationships with the following makers of anti–tumor necrosis factor agents: Abbott, Amgen, Centocor, Pfizer, and UCB.

One striking feature of this anti-TNF-induced cutaneous drug reaction is how long it takes to appear.

Source DR. MANDELL

Systemic immuno-suppression may be needed to control the psoriasis in some patients.

Source DR. GOTTLIEB

NEW ORLEANS – Induction or exacerbation of psoriasis is a common and paradoxical side effect of anti–tumor necrosis factor-alpha therapy for rheumatologic and inflammatory bowel diseases.

The paradox lies in the fact that anti-TNF agents are a tremendously effective therapy for moderate to severe psoriasis.

So when a patient with Crohn's disease or rheumatoid arthritis in remission induced by anti-TNF therapy suddenly develops severe psoriasis, it creates a clinical conundrum, observed Dr. Brian F. Mandell at the meeting Dr. Mandell is a rheumatologist who is professor and chairman of the department of medicine at the Cleveland Clinic.

Dr. Alice Gottlieb noted that psoriasis induced by TNF blockers is a class effect that, although rare, can be severe and debilitating, especially in cases of palmar-plantar psoriasis.

Unfortunately, palmar-plantar psoriasis is much more common in TNF-blocker-induced/flared psoriasis than it is in the general psoriasis population, Dr. Gottlieb said in an interview.

In his report, Dr. Mandell noted that a strikingly unusual feature of this cutaneous drug reaction is how long it takes to appear. In a recent study by European gastroenterologists and dermatologists, the median interval between the start of infliximab (Remicade) for inflammatory bowel disease (IBD) and the occurrence of psoriasis was 17 months; for adalimumab (Humira), the median interval was 12 months; and with certolizumab (Cimzia), it was 4.5 months, noted Dr. Mandell.

The European study involved 85 patients being treated with anti-TNF agents for Crohn's disease or ulcerative colitis who developed severe skin lesions while their IBD remained quiescent.

Sixty-two patients developed dermatologist-diagnosed psoriasis marked by the classic histologic features, including epidermal hyperplasia, parakeratosis, agranulosis, elongated rete ridges, and dilated dermal capillaries.

Fourteen patients had a history of psoriasis prior to anti-TNF therapy, and another 8 had a family history of the skin disease.

The most frequently affected site was the scalp, in 40 patients. A total of 27 patients had involvement at the axillae, groin, and other flexural sites, which are not typical locations for psoriasis; 21 had both scalp and flexural lesions; and 22 had palmar-plantar psoriasis.

Dr. Mandell's data shed some light on treatments: All 62 patients were promptly placed on topical therapy with corticosteroids, vitamin D analogs, keratolytics, and emollients, with phototherapy being prescribed in selected cases.

Twenty-five patients showed a favorable response, while the remaining 37 had no response at all to topical therapy.

Eighteen patients discontinued anti-TNF therapy altogether, of whom 16 experienced complete regression of their psoriasis. Twenty-six patients switched to a second TNF inhibitor; only 1 showed improvement in skin lesions.

Ten of the 23 patients who developed eczematous lesions had a history of atopy. The median duration of anti-TNF therapy prior to onset of the skin lesions was 11 months for infliximab, 6 months for adalimumab, and 14 months for certolizumab.

The histology was consistent with eczema. The lesions were equally distributed on the scalp, flexural areas, trunk, face, and limbs. Sixteen of 23 patients had a favorable response to topical steroids and emollients. Five patients were switched to a second anti-TNF biologic, but only one experienced resultant skin improvement. Four patients were eventually taken off anti-TNF therapy altogether, with complete clearing of skin lesions in a median of 3 months.

Dr. Gottlieb, chair of dermatology at the Tufts Medical Center, Boston, noted that the best clinical results are obtained when the TNF blocker is discontinued. Often systemic immunosuppression/immunomodulation is required to control psoriasis induced by a TNF blocker (J. Dermatolog. Treat. 2009;20:100-8).

Altogether, recurrent severe skin lesions caused one-third of IBD patients in this study to discontinue anti-TNF therapy. Extrapolating from the broader Lille University gastroenterology experience, the French investigators estimated that patients on anti-TNF therapy have roughly a 5% risk of developing inflammatory skin lesions, and that the need to halt biologic therapy due to an inability to gain control of the skin eruption is around 1% (Clin. Gastroenterol. Hepatol. 2010;8:1048-55).

Dr. Mandell said the European report on anti-TNF-treated IBD patients accurately reflects his own experience in using the biologics for rheumatoid arthritis, although he's had more success than the gastroenterologists in switching patients to a different agent within the anti-TNF class in order to continue with treatment.

But he noted that it's necessary to discontinue anti-TNF therapy altogether in a minority of Rheumatology patients, and even then the psoriasiform reactions don't always resolve.

Dr. Mandell said he had no relevant commercial interests. Dr. Gottlieb declared financial relationships with the following makers of anti–tumor necrosis factor agents: Abbott, Amgen, Centocor, Pfizer, and UCB.

One striking feature of this anti-TNF-induced cutaneous drug reaction is how long it takes to appear.

Source DR. MANDELL

Systemic immuno-suppression may be needed to control the psoriasis in some patients.

Source DR. GOTTLIEB

NEW ORLEANS – Induction or exacerbation of psoriasis is a common and paradoxical side effect of anti–tumor necrosis factor-alpha therapy for rheumatologic and inflammatory bowel diseases.

The paradox lies in the fact that anti-TNF agents are a tremendously effective therapy for moderate to severe psoriasis.

So when a patient with Crohn's disease or rheumatoid arthritis in remission induced by anti-TNF therapy suddenly develops severe psoriasis, it creates a clinical conundrum, observed Dr. Brian F. Mandell at the meeting Dr. Mandell is a rheumatologist who is professor and chairman of the department of medicine at the Cleveland Clinic.

Dr. Alice Gottlieb noted that psoriasis induced by TNF blockers is a class effect that, although rare, can be severe and debilitating, especially in cases of palmar-plantar psoriasis.

Unfortunately, palmar-plantar psoriasis is much more common in TNF-blocker-induced/flared psoriasis than it is in the general psoriasis population, Dr. Gottlieb said in an interview.

In his report, Dr. Mandell noted that a strikingly unusual feature of this cutaneous drug reaction is how long it takes to appear. In a recent study by European gastroenterologists and dermatologists, the median interval between the start of infliximab (Remicade) for inflammatory bowel disease (IBD) and the occurrence of psoriasis was 17 months; for adalimumab (Humira), the median interval was 12 months; and with certolizumab (Cimzia), it was 4.5 months, noted Dr. Mandell.

The European study involved 85 patients being treated with anti-TNF agents for Crohn's disease or ulcerative colitis who developed severe skin lesions while their IBD remained quiescent.

Sixty-two patients developed dermatologist-diagnosed psoriasis marked by the classic histologic features, including epidermal hyperplasia, parakeratosis, agranulosis, elongated rete ridges, and dilated dermal capillaries.

Fourteen patients had a history of psoriasis prior to anti-TNF therapy, and another 8 had a family history of the skin disease.

The most frequently affected site was the scalp, in 40 patients. A total of 27 patients had involvement at the axillae, groin, and other flexural sites, which are not typical locations for psoriasis; 21 had both scalp and flexural lesions; and 22 had palmar-plantar psoriasis.

Dr. Mandell's data shed some light on treatments: All 62 patients were promptly placed on topical therapy with corticosteroids, vitamin D analogs, keratolytics, and emollients, with phototherapy being prescribed in selected cases.

Twenty-five patients showed a favorable response, while the remaining 37 had no response at all to topical therapy.

Eighteen patients discontinued anti-TNF therapy altogether, of whom 16 experienced complete regression of their psoriasis. Twenty-six patients switched to a second TNF inhibitor; only 1 showed improvement in skin lesions.

Ten of the 23 patients who developed eczematous lesions had a history of atopy. The median duration of anti-TNF therapy prior to onset of the skin lesions was 11 months for infliximab, 6 months for adalimumab, and 14 months for certolizumab.

The histology was consistent with eczema. The lesions were equally distributed on the scalp, flexural areas, trunk, face, and limbs. Sixteen of 23 patients had a favorable response to topical steroids and emollients. Five patients were switched to a second anti-TNF biologic, but only one experienced resultant skin improvement. Four patients were eventually taken off anti-TNF therapy altogether, with complete clearing of skin lesions in a median of 3 months.

Dr. Gottlieb, chair of dermatology at the Tufts Medical Center, Boston, noted that the best clinical results are obtained when the TNF blocker is discontinued. Often systemic immunosuppression/immunomodulation is required to control psoriasis induced by a TNF blocker (J. Dermatolog. Treat. 2009;20:100-8).

Altogether, recurrent severe skin lesions caused one-third of IBD patients in this study to discontinue anti-TNF therapy. Extrapolating from the broader Lille University gastroenterology experience, the French investigators estimated that patients on anti-TNF therapy have roughly a 5% risk of developing inflammatory skin lesions, and that the need to halt biologic therapy due to an inability to gain control of the skin eruption is around 1% (Clin. Gastroenterol. Hepatol. 2010;8:1048-55).

Dr. Mandell said the European report on anti-TNF-treated IBD patients accurately reflects his own experience in using the biologics for rheumatoid arthritis, although he's had more success than the gastroenterologists in switching patients to a different agent within the anti-TNF class in order to continue with treatment.

But he noted that it's necessary to discontinue anti-TNF therapy altogether in a minority of Rheumatology patients, and even then the psoriasiform reactions don't always resolve.

Dr. Mandell said he had no relevant commercial interests. Dr. Gottlieb declared financial relationships with the following makers of anti–tumor necrosis factor agents: Abbott, Amgen, Centocor, Pfizer, and UCB.

One striking feature of this anti-TNF-induced cutaneous drug reaction is how long it takes to appear.

Source DR. MANDELL

Systemic immuno-suppression may be needed to control the psoriasis in some patients.

Source DR. GOTTLIEB

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

SNOWMASS, COLO. – Macrophage activation syndrome is a challenging diagnosis whose most useful clues are to be found in the laboratory report.

Suspect the life-threatening diagnosis of macrophage activation syndrome (MAS) in a patient with virtually any form of active rheumatologic disease who becomes acutely ill with a sharp drop in both erythrocyte sedimentation rate and platelet count in the presence of a persistently high C-reactive protein and escalating levels of serum D-dimers, urged Dr. Alexei A. Grom.

Another suggestive laboratory feature is marked hyperferritinemia. Patients with MAS often have a serum ferritin level in excess of 10,000 ng/mL, Dr. Grom said at a symposium sponsored by the American College of Rheumatology.

Moreover, while normally 60%-80% of serum ferritin is glycosylated, in MAS it’s typically less than 20%. This makes measurement of serum glycosylated ferritin a useful diagnostic tool, noted Dr. Grom, a pediatric rheumatologist at Cincinnati Children’s Hospital Medical Center.

Assessment of serum levels of soluble CD163 and soluble interleukin-2-receptor-alpha chains can also help pin down the diagnosis. They are strikingly elevated in MAS, and not in many other conditions. Extreme hypertriglyceridemia is another characteristic feature.

The central feature of MAS, he continued, is uncontrolled expansion of cytotoxic CD8 cells secreting cytokines that stimulate macrophages to exhibit hemophagocytic activity.

Indeed, hemophagocytic activity on the part of highly activated macrophages is the hallmark of MAS. Identification of hemophagocytic macrophages in the bone marrow confirms the diagnosis. Unfortunately, often this finding is not present early in the course of the disease.

This macrophage hemophagocytosis explains the extreme hyperferritinemia seen in MAS. Free hemoglobin is released as erythrocytes are phagocytized. This creates a need to boost ferritin production in order to sequestrate the free iron, he explained.

Three cardinal features of the massive systemic inflammatory response that defines MAS are liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulation. However, like hemophagocytic macrophages in the bone marrow, these features often are not of much help in making an early diagnosis. Overt cytopenia is seen only in the late stages of MAS.

Abnormal liver function tests and laboratory evidence of coagulopathy can also occur in a flare of systemic juvenile idiopathic arthritis – and since 80% of pediatric MAS occurs in patients with SJIA, hepatic dysfunction and coagulopathy are not useful in making the distinction.

The clinical presentation of MAS includes persistent fever, impressively enlarged lymph nodes, prominent hepatosplenomegaly, and a hemorrhagic rash featuring bruising, then purpura, followed by mucosal bleeding. Many patients also develop mental status changes and/or seizures. These clinical features can be viewed as largely a consequence of a cytokine storm involving increased interferon-gamma, granulocyte macrophage colony–stimulating factor, tumor necrosis factor-alpha, and interleukin-1, -6, and -18.

No trigger is identifiable in the majority of cases of MAS. When a trigger is found, it is most commonly an infection with Epstein-Barr virus or cytomegalovirus.

MAS has a 10%-20% mortality. The death rate is declining in pediatric patients because of increasing awareness of the syndrome and consequent earlier diagnosis and initiation of treatment.

"I think that in adult rheumatology this condition is still relatively unrecognized. My adult rheumatology colleagues in Cincinnati believe that many of these patients end up with a diagnosis of culture-negative sepsis," Dr. Grom said.

It’s crucial to understand that roughly one-third of patients with MAC will experience recurrent episodes. For this reason, Dr. Grom provides patients with a letter explaining their condition in the event they should have a recurrence while out of town, necessitating a visit to an emergency department where physicians may be MAC inexperienced.

Dr. Grom declared having no relevant financial interests.

SNOWMASS, COLO. – Macrophage activation syndrome is a challenging diagnosis whose most useful clues are to be found in the laboratory report.

Suspect the life-threatening diagnosis of macrophage activation syndrome (MAS) in a patient with virtually any form of active rheumatologic disease who becomes acutely ill with a sharp drop in both erythrocyte sedimentation rate and platelet count in the presence of a persistently high C-reactive protein and escalating levels of serum D-dimers, urged Dr. Alexei A. Grom.

Another suggestive laboratory feature is marked hyperferritinemia. Patients with MAS often have a serum ferritin level in excess of 10,000 ng/mL, Dr. Grom said at a symposium sponsored by the American College of Rheumatology.

Moreover, while normally 60%-80% of serum ferritin is glycosylated, in MAS it’s typically less than 20%. This makes measurement of serum glycosylated ferritin a useful diagnostic tool, noted Dr. Grom, a pediatric rheumatologist at Cincinnati Children’s Hospital Medical Center.

Assessment of serum levels of soluble CD163 and soluble interleukin-2-receptor-alpha chains can also help pin down the diagnosis. They are strikingly elevated in MAS, and not in many other conditions. Extreme hypertriglyceridemia is another characteristic feature.

The central feature of MAS, he continued, is uncontrolled expansion of cytotoxic CD8 cells secreting cytokines that stimulate macrophages to exhibit hemophagocytic activity.

Indeed, hemophagocytic activity on the part of highly activated macrophages is the hallmark of MAS. Identification of hemophagocytic macrophages in the bone marrow confirms the diagnosis. Unfortunately, often this finding is not present early in the course of the disease.

This macrophage hemophagocytosis explains the extreme hyperferritinemia seen in MAS. Free hemoglobin is released as erythrocytes are phagocytized. This creates a need to boost ferritin production in order to sequestrate the free iron, he explained.

Three cardinal features of the massive systemic inflammatory response that defines MAS are liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulation. However, like hemophagocytic macrophages in the bone marrow, these features often are not of much help in making an early diagnosis. Overt cytopenia is seen only in the late stages of MAS.

Abnormal liver function tests and laboratory evidence of coagulopathy can also occur in a flare of systemic juvenile idiopathic arthritis – and since 80% of pediatric MAS occurs in patients with SJIA, hepatic dysfunction and coagulopathy are not useful in making the distinction.

The clinical presentation of MAS includes persistent fever, impressively enlarged lymph nodes, prominent hepatosplenomegaly, and a hemorrhagic rash featuring bruising, then purpura, followed by mucosal bleeding. Many patients also develop mental status changes and/or seizures. These clinical features can be viewed as largely a consequence of a cytokine storm involving increased interferon-gamma, granulocyte macrophage colony–stimulating factor, tumor necrosis factor-alpha, and interleukin-1, -6, and -18.

No trigger is identifiable in the majority of cases of MAS. When a trigger is found, it is most commonly an infection with Epstein-Barr virus or cytomegalovirus.

MAS has a 10%-20% mortality. The death rate is declining in pediatric patients because of increasing awareness of the syndrome and consequent earlier diagnosis and initiation of treatment.

"I think that in adult rheumatology this condition is still relatively unrecognized. My adult rheumatology colleagues in Cincinnati believe that many of these patients end up with a diagnosis of culture-negative sepsis," Dr. Grom said.

It’s crucial to understand that roughly one-third of patients with MAC will experience recurrent episodes. For this reason, Dr. Grom provides patients with a letter explaining their condition in the event they should have a recurrence while out of town, necessitating a visit to an emergency department where physicians may be MAC inexperienced.

Dr. Grom declared having no relevant financial interests.

SNOWMASS, COLO. – Macrophage activation syndrome is a challenging diagnosis whose most useful clues are to be found in the laboratory report.

Suspect the life-threatening diagnosis of macrophage activation syndrome (MAS) in a patient with virtually any form of active rheumatologic disease who becomes acutely ill with a sharp drop in both erythrocyte sedimentation rate and platelet count in the presence of a persistently high C-reactive protein and escalating levels of serum D-dimers, urged Dr. Alexei A. Grom.

Another suggestive laboratory feature is marked hyperferritinemia. Patients with MAS often have a serum ferritin level in excess of 10,000 ng/mL, Dr. Grom said at a symposium sponsored by the American College of Rheumatology.

Moreover, while normally 60%-80% of serum ferritin is glycosylated, in MAS it’s typically less than 20%. This makes measurement of serum glycosylated ferritin a useful diagnostic tool, noted Dr. Grom, a pediatric rheumatologist at Cincinnati Children’s Hospital Medical Center.

Assessment of serum levels of soluble CD163 and soluble interleukin-2-receptor-alpha chains can also help pin down the diagnosis. They are strikingly elevated in MAS, and not in many other conditions. Extreme hypertriglyceridemia is another characteristic feature.

The central feature of MAS, he continued, is uncontrolled expansion of cytotoxic CD8 cells secreting cytokines that stimulate macrophages to exhibit hemophagocytic activity.

Indeed, hemophagocytic activity on the part of highly activated macrophages is the hallmark of MAS. Identification of hemophagocytic macrophages in the bone marrow confirms the diagnosis. Unfortunately, often this finding is not present early in the course of the disease.

This macrophage hemophagocytosis explains the extreme hyperferritinemia seen in MAS. Free hemoglobin is released as erythrocytes are phagocytized. This creates a need to boost ferritin production in order to sequestrate the free iron, he explained.

Three cardinal features of the massive systemic inflammatory response that defines MAS are liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulation. However, like hemophagocytic macrophages in the bone marrow, these features often are not of much help in making an early diagnosis. Overt cytopenia is seen only in the late stages of MAS.

Abnormal liver function tests and laboratory evidence of coagulopathy can also occur in a flare of systemic juvenile idiopathic arthritis – and since 80% of pediatric MAS occurs in patients with SJIA, hepatic dysfunction and coagulopathy are not useful in making the distinction.

The clinical presentation of MAS includes persistent fever, impressively enlarged lymph nodes, prominent hepatosplenomegaly, and a hemorrhagic rash featuring bruising, then purpura, followed by mucosal bleeding. Many patients also develop mental status changes and/or seizures. These clinical features can be viewed as largely a consequence of a cytokine storm involving increased interferon-gamma, granulocyte macrophage colony–stimulating factor, tumor necrosis factor-alpha, and interleukin-1, -6, and -18.

No trigger is identifiable in the majority of cases of MAS. When a trigger is found, it is most commonly an infection with Epstein-Barr virus or cytomegalovirus.

MAS has a 10%-20% mortality. The death rate is declining in pediatric patients because of increasing awareness of the syndrome and consequent earlier diagnosis and initiation of treatment.

"I think that in adult rheumatology this condition is still relatively unrecognized. My adult rheumatology colleagues in Cincinnati believe that many of these patients end up with a diagnosis of culture-negative sepsis," Dr. Grom said.

It’s crucial to understand that roughly one-third of patients with MAC will experience recurrent episodes. For this reason, Dr. Grom provides patients with a letter explaining their condition in the event they should have a recurrence while out of town, necessitating a visit to an emergency department where physicians may be MAC inexperienced.

Dr. Grom declared having no relevant financial interests.

Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.

Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.

In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).

During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.

Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.

When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.

The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.

Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.

In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.

The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).

"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).

Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.

Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.

Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.

In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).

During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.

Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.

When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.

The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.

Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.

In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.

The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).

"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).

Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.

Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.

Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.

In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).

During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.

Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.

When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.

The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.

Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.

In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.

The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).

"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).

Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Erosive progression is arrested in rheumatoid arthritis patients who are treated with adalimumab and methotrexate combination therapy, judging from results of a novel longitudinal study comparing MRI, ultrasonography, CT, and radiography.

However, only MRI was sensitive enough to document repair of individual erosions. Both MRI and ultrasound could detect changes in bone edema, which "was predictive of subsequent erosive progression on CT, both at the individual bone/joint level and also for MRI bone edema at the patient level," reported lead author Dr. Uffe Møller Døhn of the department of rheumatology at the University of Copenhagen in the February 2011 edition of the Annals of the Rheumatic Diseases. "These data emphasize the predictive value of modern imaging, and especially highlight the importance of MRI bone edema for predicting erosive progression."

The findings also offer a different way of thinking about RA’s pathology. In an accompanying editorial, Dr. Fiona McQueen and Dr. Esperanza Naredo said that the study’s findings add to existing evidence suggesting that osteitis is more strongly predictive of bone erosion than is synovitis, which supports "the notion that there is a more direct connection between bone inflammation and bone damage than between synovial inflammation and bone damage" (Ann. Rheum. Dis. 2011;70:241-4). They described synovitis and osteitis as "cousins with a common ancestor, the process that ultimately drives both remaining obscure but possibly sited in the bone marrow."

Dr. Døhn and his associates used MRI, ultrasound, standard radiography, and high-resolution CT images of the wrist and metacarpophalangeal joints 2-5 to study response to adalimumab/methotrexate therapy in 52 RA patients naive to biological agents. All images were obtained before the first dose of adalimumab injection and were repeated after 6 and 12 months of treatment (Ann. Rheum. Dis. 2011;70:252-8).

The median age of patients was 61 years, and 67% were women. From baseline, the researchers did not observe any statistically significant changes in overall bone destruction or repair at 6 or 12 months, but differences were seen when researchers used the smallest-detectable-change cutoff. For example, after 6 and 12 months, the scores of MRI synovitis, grey-scale synovitis, and power Doppler ultrasonography decreased. So did scores as assessed by DAS28 (disease activity score in 28 joints), a health assessment questionnaire, and tender and swollen joint counts.

Study participants with disease progression on CT had higher baseline MRI bone edema scores. In fact, when baseline MRI bone edema was present, the risk ratio for erosive progression in the same bone on CT at 12 months was 3.8. In addition, time-integrated MRI bone edema, power Doppler, and grey-scale synovitis scores were higher in bones and joints with CT progression.

With CT as the reference method, the researchers determined that the sensitivity and specificity for the other imaging modalities were 68% and 92%, respectively, on MRI; 44% and 95% on ultrasonography; and 26% and 98% on radiography.

In their concluding remarks in the editorial, Dr. McQueen and Dr. Naredo emphasized that the reduction of both synovitis and osteitis "is clearly an important therapeutic goal" in treating RA. "The detection and monitoring of synovitis is often more feasible in clinical practice using [ultrasound] than MRI scanning, but the latter does afford the opportunity to detect and monitor bone edema at the same time."

Dr. McQueen is with the department of molecular medicine and pathology at the University of Auckland (New Zealand). Dr. Naredo is with the department of rheumatology at the Hospital Universitario Severo Ochoa in Madrid.

Funding for the study was provided by Abbott Denmark, the Danish Rheumatism Association, and the Aase and Ejner Danielsen Foundation. Dr. Døhn reported no relevant financial conflicts, but many of the study’s coauthors disclosed that they have received consulting fees, speaking fees, or research grants from Abbott, Centocor, Roche, Schering-Plough, UCB-Nordic, and Wyeth. Dr. McQueen and Dr. Naredo stated that they have no conflicts of interest.

Erosive progression is arrested in rheumatoid arthritis patients who are treated with adalimumab and methotrexate combination therapy, judging from results of a novel longitudinal study comparing MRI, ultrasonography, CT, and radiography.

However, only MRI was sensitive enough to document repair of individual erosions. Both MRI and ultrasound could detect changes in bone edema, which "was predictive of subsequent erosive progression on CT, both at the individual bone/joint level and also for MRI bone edema at the patient level," reported lead author Dr. Uffe Møller Døhn of the department of rheumatology at the University of Copenhagen in the February 2011 edition of the Annals of the Rheumatic Diseases. "These data emphasize the predictive value of modern imaging, and especially highlight the importance of MRI bone edema for predicting erosive progression."

The findings also offer a different way of thinking about RA’s pathology. In an accompanying editorial, Dr. Fiona McQueen and Dr. Esperanza Naredo said that the study’s findings add to existing evidence suggesting that osteitis is more strongly predictive of bone erosion than is synovitis, which supports "the notion that there is a more direct connection between bone inflammation and bone damage than between synovial inflammation and bone damage" (Ann. Rheum. Dis. 2011;70:241-4). They described synovitis and osteitis as "cousins with a common ancestor, the process that ultimately drives both remaining obscure but possibly sited in the bone marrow."

Dr. Døhn and his associates used MRI, ultrasound, standard radiography, and high-resolution CT images of the wrist and metacarpophalangeal joints 2-5 to study response to adalimumab/methotrexate therapy in 52 RA patients naive to biological agents. All images were obtained before the first dose of adalimumab injection and were repeated after 6 and 12 months of treatment (Ann. Rheum. Dis. 2011;70:252-8).

The median age of patients was 61 years, and 67% were women. From baseline, the researchers did not observe any statistically significant changes in overall bone destruction or repair at 6 or 12 months, but differences were seen when researchers used the smallest-detectable-change cutoff. For example, after 6 and 12 months, the scores of MRI synovitis, grey-scale synovitis, and power Doppler ultrasonography decreased. So did scores as assessed by DAS28 (disease activity score in 28 joints), a health assessment questionnaire, and tender and swollen joint counts.

Study participants with disease progression on CT had higher baseline MRI bone edema scores. In fact, when baseline MRI bone edema was present, the risk ratio for erosive progression in the same bone on CT at 12 months was 3.8. In addition, time-integrated MRI bone edema, power Doppler, and grey-scale synovitis scores were higher in bones and joints with CT progression.

With CT as the reference method, the researchers determined that the sensitivity and specificity for the other imaging modalities were 68% and 92%, respectively, on MRI; 44% and 95% on ultrasonography; and 26% and 98% on radiography.

In their concluding remarks in the editorial, Dr. McQueen and Dr. Naredo emphasized that the reduction of both synovitis and osteitis "is clearly an important therapeutic goal" in treating RA. "The detection and monitoring of synovitis is often more feasible in clinical practice using [ultrasound] than MRI scanning, but the latter does afford the opportunity to detect and monitor bone edema at the same time."

Dr. McQueen is with the department of molecular medicine and pathology at the University of Auckland (New Zealand). Dr. Naredo is with the department of rheumatology at the Hospital Universitario Severo Ochoa in Madrid.

Funding for the study was provided by Abbott Denmark, the Danish Rheumatism Association, and the Aase and Ejner Danielsen Foundation. Dr. Døhn reported no relevant financial conflicts, but many of the study’s coauthors disclosed that they have received consulting fees, speaking fees, or research grants from Abbott, Centocor, Roche, Schering-Plough, UCB-Nordic, and Wyeth. Dr. McQueen and Dr. Naredo stated that they have no conflicts of interest.

Erosive progression is arrested in rheumatoid arthritis patients who are treated with adalimumab and methotrexate combination therapy, judging from results of a novel longitudinal study comparing MRI, ultrasonography, CT, and radiography.

However, only MRI was sensitive enough to document repair of individual erosions. Both MRI and ultrasound could detect changes in bone edema, which "was predictive of subsequent erosive progression on CT, both at the individual bone/joint level and also for MRI bone edema at the patient level," reported lead author Dr. Uffe Møller Døhn of the department of rheumatology at the University of Copenhagen in the February 2011 edition of the Annals of the Rheumatic Diseases. "These data emphasize the predictive value of modern imaging, and especially highlight the importance of MRI bone edema for predicting erosive progression."

The findings also offer a different way of thinking about RA’s pathology. In an accompanying editorial, Dr. Fiona McQueen and Dr. Esperanza Naredo said that the study’s findings add to existing evidence suggesting that osteitis is more strongly predictive of bone erosion than is synovitis, which supports "the notion that there is a more direct connection between bone inflammation and bone damage than between synovial inflammation and bone damage" (Ann. Rheum. Dis. 2011;70:241-4). They described synovitis and osteitis as "cousins with a common ancestor, the process that ultimately drives both remaining obscure but possibly sited in the bone marrow."

Dr. Døhn and his associates used MRI, ultrasound, standard radiography, and high-resolution CT images of the wrist and metacarpophalangeal joints 2-5 to study response to adalimumab/methotrexate therapy in 52 RA patients naive to biological agents. All images were obtained before the first dose of adalimumab injection and were repeated after 6 and 12 months of treatment (Ann. Rheum. Dis. 2011;70:252-8).

The median age of patients was 61 years, and 67% were women. From baseline, the researchers did not observe any statistically significant changes in overall bone destruction or repair at 6 or 12 months, but differences were seen when researchers used the smallest-detectable-change cutoff. For example, after 6 and 12 months, the scores of MRI synovitis, grey-scale synovitis, and power Doppler ultrasonography decreased. So did scores as assessed by DAS28 (disease activity score in 28 joints), a health assessment questionnaire, and tender and swollen joint counts.

Study participants with disease progression on CT had higher baseline MRI bone edema scores. In fact, when baseline MRI bone edema was present, the risk ratio for erosive progression in the same bone on CT at 12 months was 3.8. In addition, time-integrated MRI bone edema, power Doppler, and grey-scale synovitis scores were higher in bones and joints with CT progression.

With CT as the reference method, the researchers determined that the sensitivity and specificity for the other imaging modalities were 68% and 92%, respectively, on MRI; 44% and 95% on ultrasonography; and 26% and 98% on radiography.

In their concluding remarks in the editorial, Dr. McQueen and Dr. Naredo emphasized that the reduction of both synovitis and osteitis "is clearly an important therapeutic goal" in treating RA. "The detection and monitoring of synovitis is often more feasible in clinical practice using [ultrasound] than MRI scanning, but the latter does afford the opportunity to detect and monitor bone edema at the same time."

Dr. McQueen is with the department of molecular medicine and pathology at the University of Auckland (New Zealand). Dr. Naredo is with the department of rheumatology at the Hospital Universitario Severo Ochoa in Madrid.

Funding for the study was provided by Abbott Denmark, the Danish Rheumatism Association, and the Aase and Ejner Danielsen Foundation. Dr. Døhn reported no relevant financial conflicts, but many of the study’s coauthors disclosed that they have received consulting fees, speaking fees, or research grants from Abbott, Centocor, Roche, Schering-Plough, UCB-Nordic, and Wyeth. Dr. McQueen and Dr. Naredo stated that they have no conflicts of interest.

The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.

The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University and his coauthors wrote in the March issue of Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011;70:404-13).

One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.

The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale) and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.

The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.

The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.

The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.

In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3). "The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician’s (swollen and tender joint counts) and patient’s (global health score) judgments together with laboratory data (CRP)."

The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that’s the next step – their uses in clinical practice settings are limited. The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings. "Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting." Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.

However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients. Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biologics therapy has been represented in one or more treatment arms.

The new definitions also "represent another successful ACR-EULAR collaboration," said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark. And, they added, "With ‘treat to target’ as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission."

They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice. "The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time."

The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.

The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.

The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University and his coauthors wrote in the March issue of Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011;70:404-13).

One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.

The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale) and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.

The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.

The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.

The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.

In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3). "The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician’s (swollen and tender joint counts) and patient’s (global health score) judgments together with laboratory data (CRP)."

The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that’s the next step – their uses in clinical practice settings are limited. The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings. "Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting." Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.

However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients. Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biologics therapy has been represented in one or more treatment arms.

The new definitions also "represent another successful ACR-EULAR collaboration," said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark. And, they added, "With ‘treat to target’ as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission."

They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice. "The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time."

The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.

The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.

The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University and his coauthors wrote in the March issue of Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011;70:404-13).

One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.

The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale) and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.

The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.

The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.

The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.

In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3). "The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician’s (swollen and tender joint counts) and patient’s (global health score) judgments together with laboratory data (CRP)."

The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that’s the next step – their uses in clinical practice settings are limited. The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings. "Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting." Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.

However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients. Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biologics therapy has been represented in one or more treatment arms.

The new definitions also "represent another successful ACR-EULAR collaboration," said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark. And, they added, "With ‘treat to target’ as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission."

They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice. "The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time."

The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.

ATLANTA – Nonbiologic disease-modifying anti-rheumatic drugs – particularly methotrexate – and treat-to-target strategies are at least as responsible as are biologic agents for improvements in the control of rheumatoid arthritis over the last 2 decades.

Data from 1989 to 2008 for 992 patients from the Nijmegen Inception Cohort of patients with newly diagnosed RA showed that the use of biologics increased from 0% around 2000 to 22%, Dr. Wietske Kievit reported at the annual meeting of the American College of Rheumatology.

During the same time period, the use of sulfasalazine decreased from 60% to 16%, with the greatest decline beginning around 2000. Also, the use of methotrexate increased from about 5% to 62%, with the sharpest increases occurring before the biologic era.

"We also saw an increase in the mean dose of methotrexate in the population; in 1989, the mean dose was almost 7 [mg/week] with a maximum of 7.5, and in 2008, the mean dose was 16 with a maximum dose of 30," said Dr. Kievit of Radboud University Nijmegen Medical Centre, the Netherlands.

Estimated mean Disease Activity Scores in 28 joints (DAS28) decreased from 4.3 to 3.2 from 1989 to 2008. The decline in estimated scores was fairly steady over time, and began before the start of the biologic era. A similar trend was seen with functional disability scores, which started at 0.65, and ended at 0.5, with the decreases beginning before the start of the biologic era.

Mean joint damage (Ratingen) scores decreased from 90% in 1989 to 50% in 2005, the last year that data were available for this measure, Dr. Kievit noted. Mean joint damage scores were much lower in the more recent years of follow-up.

She and her colleagues also looked at the number of orthopedic surgeries in the cohort over time. There were 13 surgeries in 197 patients in 1991 (incidence rate 0.07) and 14 in 728 patients in 2008 (incidence rate 0.02).

Patients in the cohort were from two centers in the Netherlands. Patients with newly diagnosed RA were entered into the cohort each year, for a total of 992 patients representing 8419 patient years of follow-up.

Rheumatoid factor and gender did not differ by year, and mean age increased from 56 years in 1989 to 61 years in 2008. Mean disease duration increased from 1.9 to 8.1 years across the study period.

Outcomes were compared by cohort year, and data were adjusted for differences in patient characteristics.

While secular trends, improvements in lifestyle (such as quitting tobacco use), or earlier referrals for specialty care later in the study period could provide an explanation for the improvements in RA control over time, the "most straightforward explanation is the introduction of biologics and tight control strategies, but also enhanced use of methotrexate and other DMARDs already available since the 1980s," Dr. Kievit said.

Neither Dr. Kievit nor any of her coauthors had any financial disclosures related to the presentation of these findings.

ATLANTA – Nonbiologic disease-modifying anti-rheumatic drugs – particularly methotrexate – and treat-to-target strategies are at least as responsible as are biologic agents for improvements in the control of rheumatoid arthritis over the last 2 decades.

Data from 1989 to 2008 for 992 patients from the Nijmegen Inception Cohort of patients with newly diagnosed RA showed that the use of biologics increased from 0% around 2000 to 22%, Dr. Wietske Kievit reported at the annual meeting of the American College of Rheumatology.

During the same time period, the use of sulfasalazine decreased from 60% to 16%, with the greatest decline beginning around 2000. Also, the use of methotrexate increased from about 5% to 62%, with the sharpest increases occurring before the biologic era.

"We also saw an increase in the mean dose of methotrexate in the population; in 1989, the mean dose was almost 7 [mg/week] with a maximum of 7.5, and in 2008, the mean dose was 16 with a maximum dose of 30," said Dr. Kievit of Radboud University Nijmegen Medical Centre, the Netherlands.

Estimated mean Disease Activity Scores in 28 joints (DAS28) decreased from 4.3 to 3.2 from 1989 to 2008. The decline in estimated scores was fairly steady over time, and began before the start of the biologic era. A similar trend was seen with functional disability scores, which started at 0.65, and ended at 0.5, with the decreases beginning before the start of the biologic era.

Mean joint damage (Ratingen) scores decreased from 90% in 1989 to 50% in 2005, the last year that data were available for this measure, Dr. Kievit noted. Mean joint damage scores were much lower in the more recent years of follow-up.

She and her colleagues also looked at the number of orthopedic surgeries in the cohort over time. There were 13 surgeries in 197 patients in 1991 (incidence rate 0.07) and 14 in 728 patients in 2008 (incidence rate 0.02).

Patients in the cohort were from two centers in the Netherlands. Patients with newly diagnosed RA were entered into the cohort each year, for a total of 992 patients representing 8419 patient years of follow-up.

Rheumatoid factor and gender did not differ by year, and mean age increased from 56 years in 1989 to 61 years in 2008. Mean disease duration increased from 1.9 to 8.1 years across the study period.

Outcomes were compared by cohort year, and data were adjusted for differences in patient characteristics.

While secular trends, improvements in lifestyle (such as quitting tobacco use), or earlier referrals for specialty care later in the study period could provide an explanation for the improvements in RA control over time, the "most straightforward explanation is the introduction of biologics and tight control strategies, but also enhanced use of methotrexate and other DMARDs already available since the 1980s," Dr. Kievit said.

Neither Dr. Kievit nor any of her coauthors had any financial disclosures related to the presentation of these findings.

ATLANTA – Nonbiologic disease-modifying anti-rheumatic drugs – particularly methotrexate – and treat-to-target strategies are at least as responsible as are biologic agents for improvements in the control of rheumatoid arthritis over the last 2 decades.

Data from 1989 to 2008 for 992 patients from the Nijmegen Inception Cohort of patients with newly diagnosed RA showed that the use of biologics increased from 0% around 2000 to 22%, Dr. Wietske Kievit reported at the annual meeting of the American College of Rheumatology.

During the same time period, the use of sulfasalazine decreased from 60% to 16%, with the greatest decline beginning around 2000. Also, the use of methotrexate increased from about 5% to 62%, with the sharpest increases occurring before the biologic era.

"We also saw an increase in the mean dose of methotrexate in the population; in 1989, the mean dose was almost 7 [mg/week] with a maximum of 7.5, and in 2008, the mean dose was 16 with a maximum dose of 30," said Dr. Kievit of Radboud University Nijmegen Medical Centre, the Netherlands.

Estimated mean Disease Activity Scores in 28 joints (DAS28) decreased from 4.3 to 3.2 from 1989 to 2008. The decline in estimated scores was fairly steady over time, and began before the start of the biologic era. A similar trend was seen with functional disability scores, which started at 0.65, and ended at 0.5, with the decreases beginning before the start of the biologic era.

Mean joint damage (Ratingen) scores decreased from 90% in 1989 to 50% in 2005, the last year that data were available for this measure, Dr. Kievit noted. Mean joint damage scores were much lower in the more recent years of follow-up.

She and her colleagues also looked at the number of orthopedic surgeries in the cohort over time. There were 13 surgeries in 197 patients in 1991 (incidence rate 0.07) and 14 in 728 patients in 2008 (incidence rate 0.02).

Patients in the cohort were from two centers in the Netherlands. Patients with newly diagnosed RA were entered into the cohort each year, for a total of 992 patients representing 8419 patient years of follow-up.

Rheumatoid factor and gender did not differ by year, and mean age increased from 56 years in 1989 to 61 years in 2008. Mean disease duration increased from 1.9 to 8.1 years across the study period.

Outcomes were compared by cohort year, and data were adjusted for differences in patient characteristics.

While secular trends, improvements in lifestyle (such as quitting tobacco use), or earlier referrals for specialty care later in the study period could provide an explanation for the improvements in RA control over time, the "most straightforward explanation is the introduction of biologics and tight control strategies, but also enhanced use of methotrexate and other DMARDs already available since the 1980s," Dr. Kievit said.

Neither Dr. Kievit nor any of her coauthors had any financial disclosures related to the presentation of these findings.

Inactivated flu vaccine is an option for patients with autoimmune inflammatory rheumatic diseases, but any vaccination should occur during periods of stable disease, according to new recommendations from the European League Against Rheumatism.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for infections, but vaccination can cause flares of the disease, wrote Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands), and colleagues. To help rheum-atologists make informed decisions about patient vaccinations, EULAR convened a task force that developed 13 evidence-based recommendations (Ann. Rheum. Dis. 2011;70:414-22).

“For the most part, such recommendations have been lacking and the field has been changing very quickly as new drugs are developed and roll into the marketplace,” according to infectious disease specialist Dr. Kevin Winthrop of the Oregon Health and Science University in Portland.

“New drugs and new vaccines make these recommendations a moving target, and it was extremely important for the expert group to sit down, review the latest data, and codify their thoughts.

“For the most part, there is a lack of data regarding the efficacy and utility of many of these vaccines in these patients, and it is often unclear how their immunosuppressive medications and underlying diseases affect vaccine responsiveness.

“With certain biologics, we know that some vaccines are diminished in their immunogenicity and it is important to clarify for physicians when these vaccines can and should be given,” he said. The expert committee members represented 11 European countries.

They reviewed studies from 1966 through October 2009, as well as abstracts presented at EULAR in 2008 and 2009 and at the American College of Rheumatology annual meeting in 2007 and 2008.

Their evidence-based recommendations on the use of vaccination in adults with AIIRDs include:

▸ Assess vaccination status of an AIIRD patient at an initial work-up.

▸ Vaccinate patients during times of stable disease whenever possible.

▸ Avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

▸ Vaccinate patients before starting B-cell–depleting biologic therapy if possible, but vaccines can be given during the use of DMARDs and TNFi agents.

▸ Strongly consider inactivated flu vaccine for patients with AIIRD.

▸ Strongly consider PPV23 (23-valent pneumococcal polysaccharide vaccination) for AIIRD patients.

▸ Vaccinate AIIRD patients for tetanus toxoid in accordance with recommendations for the general population.

▸ Consider herpes zoster vaccination in AIIRD patients.

▸ Consider human papillomavirus vaccination for selected patients with AIIRD (young women with systemic lupus erythematosus up to age 25 years).

▸ Vaccinate hyposplenic or asplenic patients who have AIIRD with vaccines for influenza, pneumococcal, Haemophilus influenzae type b, and meningococcal C.

▸ Vaccinate only at-risk AIIRD patients for hepatitis A and/or hepatitis B.

▸ Vaccinate traveling AIIRD patients according to the general rules for travelers, but avoid the use of live, attenuated vaccines whenever possible in those patients who are immunosuppressed.

▸ Do not vaccinate AIIRD patients with the BCG vaccine.

In an interview with

“Clearly, we need better information regarding the risk of vaccine-preventable diseases in this population, as well as the outcomes of such infections and how these outcomes are modulated by certain immunosuppressive therapies [that are used in patients with AIIRDs].

“Such research would help better clarify the potential benefits of vaccination.

“On the adverse event side, further research is certainly necessary to better understand the risk of such vaccines (particularly live vaccines) and how that risk is modulated by immunosuppressive therapies, most notably biologic therapies.

“Lastly, studies evaluating the safety and efficacy of new vaccines [such as zoster vaccine and the new conjugated pneumococcal vaccine PCV13] in the context of existing and new biologic therapies remains an important area of study,” Dr. Winthrop noted.

The study that produced the guidelines was funded by the European League Against Rheumatism. The researchers had no financial conflicts to disclose. Dr. Winthrop said he had no relevant financial disclosures to make.

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Zoster Vaccine Needs Evaluation in AIIRD

Because of the immune dysregulation seen inpatients with AIIRD, some vaccine-preventable infections seem to be more common or more severe. Yet the immunosuppressive therapies given to these patients can blunt the vaccine efficacy or, theoretically, be associated with primary infection from certain live and attenuated vaccines. There is only a limited amount of information obtained in the controlled-trial setting to provide guidance. Hence, a structured review of published data with expert discussion is of value in helping to provide guidance as to when specific vaccination is either appropriate or should be avoided. This is a common question from our patients: “Should I get [a specific vaccine]?”

The likelihood of a patient's getting a severe infection without having gotten a vaccine, the degree of immunosuppression, and the safety of the vaccine are all factors that rheumatologists should consider when counseling patients about vaccinations. Influenza and pneumococcal vaccine decisions are easy: Efficacy may be blunted in some settings, but the vaccines are safe and any potential efficacy would be beneficial. A decision to vaccinate patients who are about to receive rituximab must take into consideration the data that B-cell–directed therapy clearly lowers the efficacy of the vaccine, so vaccination ideally should be given prior to this therapy. This takes some planning and careful review of the patient's vaccination history in advance. We need outcome-based studies of clinical, not just serologic, efficacy of certain vaccines in the setting of immunosuppression. I would particularly like to see formal studies on safety and efficacy of the zoster vaccine.

Inactivated flu vaccine is an option for patients with autoimmune inflammatory rheumatic diseases, but any vaccination should occur during periods of stable disease, according to new recommendations from the European League Against Rheumatism.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for infections, but vaccination can cause flares of the disease, wrote Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands), and colleagues. To help rheum-atologists make informed decisions about patient vaccinations, EULAR convened a task force that developed 13 evidence-based recommendations (Ann. Rheum. Dis. 2011;70:414-22).

“For the most part, such recommendations have been lacking and the field has been changing very quickly as new drugs are developed and roll into the marketplace,” according to infectious disease specialist Dr. Kevin Winthrop of the Oregon Health and Science University in Portland.

“New drugs and new vaccines make these recommendations a moving target, and it was extremely important for the expert group to sit down, review the latest data, and codify their thoughts.

“For the most part, there is a lack of data regarding the efficacy and utility of many of these vaccines in these patients, and it is often unclear how their immunosuppressive medications and underlying diseases affect vaccine responsiveness.

“With certain biologics, we know that some vaccines are diminished in their immunogenicity and it is important to clarify for physicians when these vaccines can and should be given,” he said. The expert committee members represented 11 European countries.

They reviewed studies from 1966 through October 2009, as well as abstracts presented at EULAR in 2008 and 2009 and at the American College of Rheumatology annual meeting in 2007 and 2008.

Their evidence-based recommendations on the use of vaccination in adults with AIIRDs include:

▸ Assess vaccination status of an AIIRD patient at an initial work-up.

▸ Vaccinate patients during times of stable disease whenever possible.

▸ Avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

▸ Vaccinate patients before starting B-cell–depleting biologic therapy if possible, but vaccines can be given during the use of DMARDs and TNFi agents.

▸ Strongly consider inactivated flu vaccine for patients with AIIRD.

▸ Strongly consider PPV23 (23-valent pneumococcal polysaccharide vaccination) for AIIRD patients.

▸ Vaccinate AIIRD patients for tetanus toxoid in accordance with recommendations for the general population.

▸ Consider herpes zoster vaccination in AIIRD patients.

▸ Consider human papillomavirus vaccination for selected patients with AIIRD (young women with systemic lupus erythematosus up to age 25 years).

▸ Vaccinate hyposplenic or asplenic patients who have AIIRD with vaccines for influenza, pneumococcal, Haemophilus influenzae type b, and meningococcal C.

▸ Vaccinate only at-risk AIIRD patients for hepatitis A and/or hepatitis B.

▸ Vaccinate traveling AIIRD patients according to the general rules for travelers, but avoid the use of live, attenuated vaccines whenever possible in those patients who are immunosuppressed.

▸ Do not vaccinate AIIRD patients with the BCG vaccine.

In an interview with

“Clearly, we need better information regarding the risk of vaccine-preventable diseases in this population, as well as the outcomes of such infections and how these outcomes are modulated by certain immunosuppressive therapies [that are used in patients with AIIRDs].

“Such research would help better clarify the potential benefits of vaccination.

“On the adverse event side, further research is certainly necessary to better understand the risk of such vaccines (particularly live vaccines) and how that risk is modulated by immunosuppressive therapies, most notably biologic therapies.

“Lastly, studies evaluating the safety and efficacy of new vaccines [such as zoster vaccine and the new conjugated pneumococcal vaccine PCV13] in the context of existing and new biologic therapies remains an important area of study,” Dr. Winthrop noted.

The study that produced the guidelines was funded by the European League Against Rheumatism. The researchers had no financial conflicts to disclose. Dr. Winthrop said he had no relevant financial disclosures to make.

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Zoster Vaccine Needs Evaluation in AIIRD

Because of the immune dysregulation seen inpatients with AIIRD, some vaccine-preventable infections seem to be more common or more severe. Yet the immunosuppressive therapies given to these patients can blunt the vaccine efficacy or, theoretically, be associated with primary infection from certain live and attenuated vaccines. There is only a limited amount of information obtained in the controlled-trial setting to provide guidance. Hence, a structured review of published data with expert discussion is of value in helping to provide guidance as to when specific vaccination is either appropriate or should be avoided. This is a common question from our patients: “Should I get [a specific vaccine]?”

The likelihood of a patient's getting a severe infection without having gotten a vaccine, the degree of immunosuppression, and the safety of the vaccine are all factors that rheumatologists should consider when counseling patients about vaccinations. Influenza and pneumococcal vaccine decisions are easy: Efficacy may be blunted in some settings, but the vaccines are safe and any potential efficacy would be beneficial. A decision to vaccinate patients who are about to receive rituximab must take into consideration the data that B-cell–directed therapy clearly lowers the efficacy of the vaccine, so vaccination ideally should be given prior to this therapy. This takes some planning and careful review of the patient's vaccination history in advance. We need outcome-based studies of clinical, not just serologic, efficacy of certain vaccines in the setting of immunosuppression. I would particularly like to see formal studies on safety and efficacy of the zoster vaccine.

Inactivated flu vaccine is an option for patients with autoimmune inflammatory rheumatic diseases, but any vaccination should occur during periods of stable disease, according to new recommendations from the European League Against Rheumatism.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for infections, but vaccination can cause flares of the disease, wrote Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands), and colleagues. To help rheum-atologists make informed decisions about patient vaccinations, EULAR convened a task force that developed 13 evidence-based recommendations (Ann. Rheum. Dis. 2011;70:414-22).

“For the most part, such recommendations have been lacking and the field has been changing very quickly as new drugs are developed and roll into the marketplace,” according to infectious disease specialist Dr. Kevin Winthrop of the Oregon Health and Science University in Portland.

“New drugs and new vaccines make these recommendations a moving target, and it was extremely important for the expert group to sit down, review the latest data, and codify their thoughts.

“For the most part, there is a lack of data regarding the efficacy and utility of many of these vaccines in these patients, and it is often unclear how their immunosuppressive medications and underlying diseases affect vaccine responsiveness.

“With certain biologics, we know that some vaccines are diminished in their immunogenicity and it is important to clarify for physicians when these vaccines can and should be given,” he said. The expert committee members represented 11 European countries.

They reviewed studies from 1966 through October 2009, as well as abstracts presented at EULAR in 2008 and 2009 and at the American College of Rheumatology annual meeting in 2007 and 2008.

Their evidence-based recommendations on the use of vaccination in adults with AIIRDs include:

▸ Assess vaccination status of an AIIRD patient at an initial work-up.

▸ Vaccinate patients during times of stable disease whenever possible.

▸ Avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

▸ Vaccinate patients before starting B-cell–depleting biologic therapy if possible, but vaccines can be given during the use of DMARDs and TNFi agents.

▸ Strongly consider inactivated flu vaccine for patients with AIIRD.

▸ Strongly consider PPV23 (23-valent pneumococcal polysaccharide vaccination) for AIIRD patients.

▸ Vaccinate AIIRD patients for tetanus toxoid in accordance with recommendations for the general population.

▸ Consider herpes zoster vaccination in AIIRD patients.

▸ Consider human papillomavirus vaccination for selected patients with AIIRD (young women with systemic lupus erythematosus up to age 25 years).

▸ Vaccinate hyposplenic or asplenic patients who have AIIRD with vaccines for influenza, pneumococcal, Haemophilus influenzae type b, and meningococcal C.

▸ Vaccinate only at-risk AIIRD patients for hepatitis A and/or hepatitis B.

▸ Vaccinate traveling AIIRD patients according to the general rules for travelers, but avoid the use of live, attenuated vaccines whenever possible in those patients who are immunosuppressed.

▸ Do not vaccinate AIIRD patients with the BCG vaccine.

In an interview with

“Clearly, we need better information regarding the risk of vaccine-preventable diseases in this population, as well as the outcomes of such infections and how these outcomes are modulated by certain immunosuppressive therapies [that are used in patients with AIIRDs].

“Such research would help better clarify the potential benefits of vaccination.

“On the adverse event side, further research is certainly necessary to better understand the risk of such vaccines (particularly live vaccines) and how that risk is modulated by immunosuppressive therapies, most notably biologic therapies.

“Lastly, studies evaluating the safety and efficacy of new vaccines [such as zoster vaccine and the new conjugated pneumococcal vaccine PCV13] in the context of existing and new biologic therapies remains an important area of study,” Dr. Winthrop noted.

The study that produced the guidelines was funded by the European League Against Rheumatism. The researchers had no financial conflicts to disclose. Dr. Winthrop said he had no relevant financial disclosures to make.

View on the News

Zoster Vaccine Needs Evaluation in AIIRD

Because of the immune dysregulation seen inpatients with AIIRD, some vaccine-preventable infections seem to be more common or more severe. Yet the immunosuppressive therapies given to these patients can blunt the vaccine efficacy or, theoretically, be associated with primary infection from certain live and attenuated vaccines. There is only a limited amount of information obtained in the controlled-trial setting to provide guidance. Hence, a structured review of published data with expert discussion is of value in helping to provide guidance as to when specific vaccination is either appropriate or should be avoided. This is a common question from our patients: “Should I get [a specific vaccine]?”

The likelihood of a patient's getting a severe infection without having gotten a vaccine, the degree of immunosuppression, and the safety of the vaccine are all factors that rheumatologists should consider when counseling patients about vaccinations. Influenza and pneumococcal vaccine decisions are easy: Efficacy may be blunted in some settings, but the vaccines are safe and any potential efficacy would be beneficial. A decision to vaccinate patients who are about to receive rituximab must take into consideration the data that B-cell–directed therapy clearly lowers the efficacy of the vaccine, so vaccination ideally should be given prior to this therapy. This takes some planning and careful review of the patient's vaccination history in advance. We need outcome-based studies of clinical, not just serologic, efficacy of certain vaccines in the setting of immunosuppression. I would particularly like to see formal studies on safety and efficacy of the zoster vaccine.