Spondyloarthropathies

NEW YORK – Late initiation of tumor necrosis factor inhibitors in patients with ankylosing spondylitis more than doubles their risk of radiographic worsening, according to a prospective study that provides insight into the natural history of this disease.

"We are probably looking at a window of opportunity. If we capture patients with more acute lesions, we may be able to inhibit the processes that drive progression that cannot be reversed once the lesions are more mature," reported Dr. Nigil Haroon of the division of rheumatology at the University of Toronto.

The data presented by Dr. Haroon were characterized as the first to show a clear association between reduced ankylosing spondylitis (AS) damage and tumor necrosis factor (TNF) overall and early initiation of TNF inhibitors specifically. According to Dr. Haroon, earlier studies have not shown this association because of inadequate follow-up.

"AS is slowly progressive. Two years is not enough to see an effect," said Dr. Haroon, who noted that most TNF inhibitor trials have not exceeded this period. He believes at least 4 years of follow-up are needed.

Long follow-up is particularly relevant for showing benefit from anti-inflammatory therapy if, as described by Dr. Haroon, sustained inflammation is required to induce vertebral fat infiltration and if, in turn, this infiltration promotes formation of syndesmophytes. However, from the clinical perspective, there is now at least some evidence that early is better than late initiation of TNF inhibitors in AS patients at risk for progressive disease.

The clinical evidence is drawn from a five-center study with 334 patients published late last year and updated by Dr. Haroon at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (Arthritis Rheum. 2013;65:2645-54). However, Dr. Haroon primarily focused on the significance of these data as they relate to the natural history of AS.

In the study, the goal was to evaluate the impact of TNF inhibitors on spinal damage in AS. Overall, TNF inhibitors, vs. no TNF inhibitors, were associated with a 48% reduction in the odds of radiographic progression (P = .02), but the timing of TNF inhibitors was an independent predictor of benefit. In those who initiated TNF inhibitors 10 or more years after disease onset, the odds of progression was increased 2.4-fold (P = .03) relative to an earlier start. Duration of TNF inhibitor therapy was also inversely correlated with progression.

These findings are highly consistent with an independent series of studies conducted by Dr. Haroon and others who have linked sustained inflammation with vertebral fat infiltration. Visible on MRI, fat infiltration at the vertebral corners has been linked to metaplasia and the de novo syndesmophyte formation that characterizes radiographic progression.

"We are not 100% sure that inflammation and new bone formation are linked, but the evidence is accumulating," Dr. Haroon reported. The theory supported by the clinical study is that early control of inflammation aborts the pathologic process that leads first to vertebral fat infiltration and then to syndesmophyte formation.

Not all AS patients may benefit equally from TNF inhibitors from the perspective of disease progression. In the five-center study data presented by Dr. Haroon, only 30.5% of the patients experienced progression, defined by having at least a one unit per year increase in the mSASSS (modified Stokes AS Spine Score). Elevated baseline inflammatory markers, such as C-reactive protein, and smoking, for which there was a dose effect, were associated with progression after researchers controlled for baseline mSASSS totals. Other factors, particularly genetics, have also been strongly linked to risk of progression in AS.

Dr. Haroon reported no relevant financial relationships.

NEW YORK – Late initiation of tumor necrosis factor inhibitors in patients with ankylosing spondylitis more than doubles their risk of radiographic worsening, according to a prospective study that provides insight into the natural history of this disease.

"We are probably looking at a window of opportunity. If we capture patients with more acute lesions, we may be able to inhibit the processes that drive progression that cannot be reversed once the lesions are more mature," reported Dr. Nigil Haroon of the division of rheumatology at the University of Toronto.

The data presented by Dr. Haroon were characterized as the first to show a clear association between reduced ankylosing spondylitis (AS) damage and tumor necrosis factor (TNF) overall and early initiation of TNF inhibitors specifically. According to Dr. Haroon, earlier studies have not shown this association because of inadequate follow-up.

"AS is slowly progressive. Two years is not enough to see an effect," said Dr. Haroon, who noted that most TNF inhibitor trials have not exceeded this period. He believes at least 4 years of follow-up are needed.

Long follow-up is particularly relevant for showing benefit from anti-inflammatory therapy if, as described by Dr. Haroon, sustained inflammation is required to induce vertebral fat infiltration and if, in turn, this infiltration promotes formation of syndesmophytes. However, from the clinical perspective, there is now at least some evidence that early is better than late initiation of TNF inhibitors in AS patients at risk for progressive disease.

The clinical evidence is drawn from a five-center study with 334 patients published late last year and updated by Dr. Haroon at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (Arthritis Rheum. 2013;65:2645-54). However, Dr. Haroon primarily focused on the significance of these data as they relate to the natural history of AS.

In the study, the goal was to evaluate the impact of TNF inhibitors on spinal damage in AS. Overall, TNF inhibitors, vs. no TNF inhibitors, were associated with a 48% reduction in the odds of radiographic progression (P = .02), but the timing of TNF inhibitors was an independent predictor of benefit. In those who initiated TNF inhibitors 10 or more years after disease onset, the odds of progression was increased 2.4-fold (P = .03) relative to an earlier start. Duration of TNF inhibitor therapy was also inversely correlated with progression.

These findings are highly consistent with an independent series of studies conducted by Dr. Haroon and others who have linked sustained inflammation with vertebral fat infiltration. Visible on MRI, fat infiltration at the vertebral corners has been linked to metaplasia and the de novo syndesmophyte formation that characterizes radiographic progression.

"We are not 100% sure that inflammation and new bone formation are linked, but the evidence is accumulating," Dr. Haroon reported. The theory supported by the clinical study is that early control of inflammation aborts the pathologic process that leads first to vertebral fat infiltration and then to syndesmophyte formation.

Not all AS patients may benefit equally from TNF inhibitors from the perspective of disease progression. In the five-center study data presented by Dr. Haroon, only 30.5% of the patients experienced progression, defined by having at least a one unit per year increase in the mSASSS (modified Stokes AS Spine Score). Elevated baseline inflammatory markers, such as C-reactive protein, and smoking, for which there was a dose effect, were associated with progression after researchers controlled for baseline mSASSS totals. Other factors, particularly genetics, have also been strongly linked to risk of progression in AS.

Dr. Haroon reported no relevant financial relationships.

NEW YORK – Late initiation of tumor necrosis factor inhibitors in patients with ankylosing spondylitis more than doubles their risk of radiographic worsening, according to a prospective study that provides insight into the natural history of this disease.

"We are probably looking at a window of opportunity. If we capture patients with more acute lesions, we may be able to inhibit the processes that drive progression that cannot be reversed once the lesions are more mature," reported Dr. Nigil Haroon of the division of rheumatology at the University of Toronto.

The data presented by Dr. Haroon were characterized as the first to show a clear association between reduced ankylosing spondylitis (AS) damage and tumor necrosis factor (TNF) overall and early initiation of TNF inhibitors specifically. According to Dr. Haroon, earlier studies have not shown this association because of inadequate follow-up.

"AS is slowly progressive. Two years is not enough to see an effect," said Dr. Haroon, who noted that most TNF inhibitor trials have not exceeded this period. He believes at least 4 years of follow-up are needed.

Long follow-up is particularly relevant for showing benefit from anti-inflammatory therapy if, as described by Dr. Haroon, sustained inflammation is required to induce vertebral fat infiltration and if, in turn, this infiltration promotes formation of syndesmophytes. However, from the clinical perspective, there is now at least some evidence that early is better than late initiation of TNF inhibitors in AS patients at risk for progressive disease.

The clinical evidence is drawn from a five-center study with 334 patients published late last year and updated by Dr. Haroon at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (Arthritis Rheum. 2013;65:2645-54). However, Dr. Haroon primarily focused on the significance of these data as they relate to the natural history of AS.

In the study, the goal was to evaluate the impact of TNF inhibitors on spinal damage in AS. Overall, TNF inhibitors, vs. no TNF inhibitors, were associated with a 48% reduction in the odds of radiographic progression (P = .02), but the timing of TNF inhibitors was an independent predictor of benefit. In those who initiated TNF inhibitors 10 or more years after disease onset, the odds of progression was increased 2.4-fold (P = .03) relative to an earlier start. Duration of TNF inhibitor therapy was also inversely correlated with progression.

These findings are highly consistent with an independent series of studies conducted by Dr. Haroon and others who have linked sustained inflammation with vertebral fat infiltration. Visible on MRI, fat infiltration at the vertebral corners has been linked to metaplasia and the de novo syndesmophyte formation that characterizes radiographic progression.

"We are not 100% sure that inflammation and new bone formation are linked, but the evidence is accumulating," Dr. Haroon reported. The theory supported by the clinical study is that early control of inflammation aborts the pathologic process that leads first to vertebral fat infiltration and then to syndesmophyte formation.

Not all AS patients may benefit equally from TNF inhibitors from the perspective of disease progression. In the five-center study data presented by Dr. Haroon, only 30.5% of the patients experienced progression, defined by having at least a one unit per year increase in the mSASSS (modified Stokes AS Spine Score). Elevated baseline inflammatory markers, such as C-reactive protein, and smoking, for which there was a dose effect, were associated with progression after researchers controlled for baseline mSASSS totals. Other factors, particularly genetics, have also been strongly linked to risk of progression in AS.

Dr. Haroon reported no relevant financial relationships.

NEW YORK – After instruction by a nurse, patients with psoriatic arthritis do at least as well as nurses but better than physicians in counting tender and swollen joints, according to a cross-sectional study that employed ultrasound as a gold standard.

"Patient counts of swollen joints correlated with both effusion and synovitis as detected by ultrasound, suggesting that patients can learn to monitor their own disease," reported Dr. Agnes Szentpetery of the department of rheumatology at St. Vincent’s Hospital, Dublin.

In this study, described as the first ever conducted in psoriatic arthritis to compare joint counts by patients, nurses, physicians, and ultrasound (US), 50 patients with a mean age of 50 years were enrolled. All received instruction from a nurse on how to assess and count tender and swollen joints. The major focus of the correlations was in 34 joints assessed with US, although further correlations were made between patients, nurses, and physicians for 28 (JC28) and 66 swollen and 68 tender (JC 66/68) counts.

"Joint counts [confirming active disease] were higher for patients and nurses than for physicians," reported Dr. Szentpetery, who presented these data at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN). Doctor and nurse counts for swollen joints, unlike patient counts, did not correlate with US evidence of effusion, although they did for synovitis.

For tender joints, there was moderate or good agreement between patient and doctor for 11 joints, doctor and nurse for 12 joints, and patient and nurse for 19 joints. (This nurse was different from the one who provided instruction on joint counts.) However, correlation between any of these observers and US evidence of tender joints was uniformly poor.

Small joints in the hand, particularly the proximal interphalangeal joint, offered the best interobserver agreement for correlations, according to Dr. Szentpetery. Although no correlations rose above good and most were moderate between any two observers, Dr. Szentpetery stressed that patients performed at levels comparable with doctors and nurses, compared with US.

"Although this was a small study, the results support patient joint counts, and we have already begun routinely instructing patients in our clinic," Dr. Szentpetery reported.

Asked for a comment, Dr. John D. Reveille, professor of rheumatology and clinical immunogenetics at the University of Texas Health Sciences Center at Houston, said that he is remaining cautious until a larger study generates more data. He said that similar efforts to instruct patients to perform joint counts in rheumatoid arthritis failed to produce acceptable rates of accuracy.

"It may be possible to enlist patients to perform accurate joint counts if they are motivated and receive appropriate education, but you may need a special population and the right education," said Dr. Reveille, who is chair of SPARTAN’s executive committee.

However, joint counts are perceived to be so time consuming that many clinics do not perform them at all, according to Dr. Szentpetery. Moreover, she suggested that the absolute number of tender or swollen joints at any moment in time may be less important than the change in joint involvement after treatment is initiated, an outcome that may be best measured by patients.

"I agree that this is a small study, and more data are needed, but our data suggest patients may have a role in joint counts, which is an attractive strategy for reducing work for the clinicians," Dr. Szentpetery said.

Dr. Szentpetery and Dr. Reveille reported no relevant financial conflicts.

NEW YORK – After instruction by a nurse, patients with psoriatic arthritis do at least as well as nurses but better than physicians in counting tender and swollen joints, according to a cross-sectional study that employed ultrasound as a gold standard.

"Patient counts of swollen joints correlated with both effusion and synovitis as detected by ultrasound, suggesting that patients can learn to monitor their own disease," reported Dr. Agnes Szentpetery of the department of rheumatology at St. Vincent’s Hospital, Dublin.

In this study, described as the first ever conducted in psoriatic arthritis to compare joint counts by patients, nurses, physicians, and ultrasound (US), 50 patients with a mean age of 50 years were enrolled. All received instruction from a nurse on how to assess and count tender and swollen joints. The major focus of the correlations was in 34 joints assessed with US, although further correlations were made between patients, nurses, and physicians for 28 (JC28) and 66 swollen and 68 tender (JC 66/68) counts.

"Joint counts [confirming active disease] were higher for patients and nurses than for physicians," reported Dr. Szentpetery, who presented these data at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN). Doctor and nurse counts for swollen joints, unlike patient counts, did not correlate with US evidence of effusion, although they did for synovitis.

For tender joints, there was moderate or good agreement between patient and doctor for 11 joints, doctor and nurse for 12 joints, and patient and nurse for 19 joints. (This nurse was different from the one who provided instruction on joint counts.) However, correlation between any of these observers and US evidence of tender joints was uniformly poor.

Small joints in the hand, particularly the proximal interphalangeal joint, offered the best interobserver agreement for correlations, according to Dr. Szentpetery. Although no correlations rose above good and most were moderate between any two observers, Dr. Szentpetery stressed that patients performed at levels comparable with doctors and nurses, compared with US.

"Although this was a small study, the results support patient joint counts, and we have already begun routinely instructing patients in our clinic," Dr. Szentpetery reported.

Asked for a comment, Dr. John D. Reveille, professor of rheumatology and clinical immunogenetics at the University of Texas Health Sciences Center at Houston, said that he is remaining cautious until a larger study generates more data. He said that similar efforts to instruct patients to perform joint counts in rheumatoid arthritis failed to produce acceptable rates of accuracy.

"It may be possible to enlist patients to perform accurate joint counts if they are motivated and receive appropriate education, but you may need a special population and the right education," said Dr. Reveille, who is chair of SPARTAN’s executive committee.

However, joint counts are perceived to be so time consuming that many clinics do not perform them at all, according to Dr. Szentpetery. Moreover, she suggested that the absolute number of tender or swollen joints at any moment in time may be less important than the change in joint involvement after treatment is initiated, an outcome that may be best measured by patients.

"I agree that this is a small study, and more data are needed, but our data suggest patients may have a role in joint counts, which is an attractive strategy for reducing work for the clinicians," Dr. Szentpetery said.

Dr. Szentpetery and Dr. Reveille reported no relevant financial conflicts.

NEW YORK – After instruction by a nurse, patients with psoriatic arthritis do at least as well as nurses but better than physicians in counting tender and swollen joints, according to a cross-sectional study that employed ultrasound as a gold standard.

"Patient counts of swollen joints correlated with both effusion and synovitis as detected by ultrasound, suggesting that patients can learn to monitor their own disease," reported Dr. Agnes Szentpetery of the department of rheumatology at St. Vincent’s Hospital, Dublin.

In this study, described as the first ever conducted in psoriatic arthritis to compare joint counts by patients, nurses, physicians, and ultrasound (US), 50 patients with a mean age of 50 years were enrolled. All received instruction from a nurse on how to assess and count tender and swollen joints. The major focus of the correlations was in 34 joints assessed with US, although further correlations were made between patients, nurses, and physicians for 28 (JC28) and 66 swollen and 68 tender (JC 66/68) counts.

"Joint counts [confirming active disease] were higher for patients and nurses than for physicians," reported Dr. Szentpetery, who presented these data at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN). Doctor and nurse counts for swollen joints, unlike patient counts, did not correlate with US evidence of effusion, although they did for synovitis.

For tender joints, there was moderate or good agreement between patient and doctor for 11 joints, doctor and nurse for 12 joints, and patient and nurse for 19 joints. (This nurse was different from the one who provided instruction on joint counts.) However, correlation between any of these observers and US evidence of tender joints was uniformly poor.

Small joints in the hand, particularly the proximal interphalangeal joint, offered the best interobserver agreement for correlations, according to Dr. Szentpetery. Although no correlations rose above good and most were moderate between any two observers, Dr. Szentpetery stressed that patients performed at levels comparable with doctors and nurses, compared with US.

"Although this was a small study, the results support patient joint counts, and we have already begun routinely instructing patients in our clinic," Dr. Szentpetery reported.

Asked for a comment, Dr. John D. Reveille, professor of rheumatology and clinical immunogenetics at the University of Texas Health Sciences Center at Houston, said that he is remaining cautious until a larger study generates more data. He said that similar efforts to instruct patients to perform joint counts in rheumatoid arthritis failed to produce acceptable rates of accuracy.

"It may be possible to enlist patients to perform accurate joint counts if they are motivated and receive appropriate education, but you may need a special population and the right education," said Dr. Reveille, who is chair of SPARTAN’s executive committee.

However, joint counts are perceived to be so time consuming that many clinics do not perform them at all, according to Dr. Szentpetery. Moreover, she suggested that the absolute number of tender or swollen joints at any moment in time may be less important than the change in joint involvement after treatment is initiated, an outcome that may be best measured by patients.

"I agree that this is a small study, and more data are needed, but our data suggest patients may have a role in joint counts, which is an attractive strategy for reducing work for the clinicians," Dr. Szentpetery said.

Dr. Szentpetery and Dr. Reveille reported no relevant financial conflicts.

NEW YORK – There appears to be progress in the effort to convince the Food and Drug Administration that nonradiologic axial spondyloarthritis is a viable disease entity that deserves to be the target of therapeutic trials, according to an account of recent deliberations.

"We are happy that the FDA [now] agrees with the axSpA [axial spondyloarthritis] concept, the burden of disease, and the need to treat such patients," reported Dr. Atul Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health and Science University, Portland.

However, this is a process. The FDA "remains very concerned about the specificity of the ASAS [Assessment of Spondyloarthritis International Society] classification criteria," Dr. Deodhar said at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN).

Treatment trials for nonradiologic axSpA (nr-axSpA) followed the development of diagnostic criteria by ASAS in 2009 (Ann. Rheum. Dis. 2009;68:777-83). On the basis of randomized controlled trials in nr-axSpA patients with adalimumab (ABILITY-1) and both nr-axSpA and axSpA patients with certolizumab pegol (AS001), both drugs were approved by the European Medicines Agency for the treatment nr-axSpA. The same evidence, reviewed by an FDA advisory committee in July 2013, produced rejections the following October.

The major problem, according to Dr. Deodhar’s account, was that the FDA found the ASAS diagnostic criteria "overly broad," creating a potential for some low-risk patients to be prescribed therapies in which a favorable benefit-to-risk ratio could not be ensured. But the decision also denied these biologics to patients who could benefit.

"Rheumatologists were put in a difficult position, inducing some to label these patients as having ankylosing spondylitis to obtain third-party approval for therapies they needed," Dr. Deodhar observed. Concerned that patients with significant disability were being denied effective therapies, leaders of both SPARTAN and ASAS are attempting to work with the FDA to define more acceptable criteria.

In a joint letter from SPARTAN and ASAS to the FDA in early 2014 requesting a meeting, the key issues outlined for discussion included the need to recognize axSpA in general and nr-axSpA specifically as pathologies associated with significant morbidity and for which there is an unmet need for therapies.

At the meeting, held in June, both of these points and several others regarding the clinical importance of nr-axSpA and axSpA were conceded by the FDA officials, according to Dr. Deodhar. He recounted that some rheumatologists on staff at the FDA continue to see patients and were empathetic about the unmet need for therapies even while expressing concern about overuse of biologics.

The solution, in the opinion of FDA regulators, as described by Dr. Deodhar, is a better set of sensitive and specific diagnostic criteria for nr-axSpA that can reliably define those patients who benefit from biologics or other therapies when compared with the current standard of care. This is a goal now being pursued by SPARTAN in collaboration with ASAS. The American College of Rheumatology (ACR) and the European League Against Rheumatism may also be invited to participate.

The acknowledgment by the FDA that nr-axSpA is a disease entity that is poorly treated with current options is an important first step in a process that Dr. Deodhar and others believe will eventually lead to approval of tumor necrosis factor inhibitors.

Asked for a comment, Dr. David Borenstein, clinical professor of rheumatology at George Washington University Medical Center, Washington, said he is confident that diagnostic criteria acceptable to professional rheumatology organizations and the FDA will eventually be created.

"There has been some dissension about the reproducibility of the current axSpA criteria and how they might be used effectively by nonspecialists," agreed Dr. Borenstein, who is a past president of the ACR. "We need to tighten the criteria to make sure we are all talking about the same problem."

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – There appears to be progress in the effort to convince the Food and Drug Administration that nonradiologic axial spondyloarthritis is a viable disease entity that deserves to be the target of therapeutic trials, according to an account of recent deliberations.

"We are happy that the FDA [now] agrees with the axSpA [axial spondyloarthritis] concept, the burden of disease, and the need to treat such patients," reported Dr. Atul Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health and Science University, Portland.

However, this is a process. The FDA "remains very concerned about the specificity of the ASAS [Assessment of Spondyloarthritis International Society] classification criteria," Dr. Deodhar said at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN).

Treatment trials for nonradiologic axSpA (nr-axSpA) followed the development of diagnostic criteria by ASAS in 2009 (Ann. Rheum. Dis. 2009;68:777-83). On the basis of randomized controlled trials in nr-axSpA patients with adalimumab (ABILITY-1) and both nr-axSpA and axSpA patients with certolizumab pegol (AS001), both drugs were approved by the European Medicines Agency for the treatment nr-axSpA. The same evidence, reviewed by an FDA advisory committee in July 2013, produced rejections the following October.

The major problem, according to Dr. Deodhar’s account, was that the FDA found the ASAS diagnostic criteria "overly broad," creating a potential for some low-risk patients to be prescribed therapies in which a favorable benefit-to-risk ratio could not be ensured. But the decision also denied these biologics to patients who could benefit.

"Rheumatologists were put in a difficult position, inducing some to label these patients as having ankylosing spondylitis to obtain third-party approval for therapies they needed," Dr. Deodhar observed. Concerned that patients with significant disability were being denied effective therapies, leaders of both SPARTAN and ASAS are attempting to work with the FDA to define more acceptable criteria.

In a joint letter from SPARTAN and ASAS to the FDA in early 2014 requesting a meeting, the key issues outlined for discussion included the need to recognize axSpA in general and nr-axSpA specifically as pathologies associated with significant morbidity and for which there is an unmet need for therapies.

At the meeting, held in June, both of these points and several others regarding the clinical importance of nr-axSpA and axSpA were conceded by the FDA officials, according to Dr. Deodhar. He recounted that some rheumatologists on staff at the FDA continue to see patients and were empathetic about the unmet need for therapies even while expressing concern about overuse of biologics.

The solution, in the opinion of FDA regulators, as described by Dr. Deodhar, is a better set of sensitive and specific diagnostic criteria for nr-axSpA that can reliably define those patients who benefit from biologics or other therapies when compared with the current standard of care. This is a goal now being pursued by SPARTAN in collaboration with ASAS. The American College of Rheumatology (ACR) and the European League Against Rheumatism may also be invited to participate.

The acknowledgment by the FDA that nr-axSpA is a disease entity that is poorly treated with current options is an important first step in a process that Dr. Deodhar and others believe will eventually lead to approval of tumor necrosis factor inhibitors.

Asked for a comment, Dr. David Borenstein, clinical professor of rheumatology at George Washington University Medical Center, Washington, said he is confident that diagnostic criteria acceptable to professional rheumatology organizations and the FDA will eventually be created.

"There has been some dissension about the reproducibility of the current axSpA criteria and how they might be used effectively by nonspecialists," agreed Dr. Borenstein, who is a past president of the ACR. "We need to tighten the criteria to make sure we are all talking about the same problem."

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – There appears to be progress in the effort to convince the Food and Drug Administration that nonradiologic axial spondyloarthritis is a viable disease entity that deserves to be the target of therapeutic trials, according to an account of recent deliberations.

"We are happy that the FDA [now] agrees with the axSpA [axial spondyloarthritis] concept, the burden of disease, and the need to treat such patients," reported Dr. Atul Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health and Science University, Portland.

However, this is a process. The FDA "remains very concerned about the specificity of the ASAS [Assessment of Spondyloarthritis International Society] classification criteria," Dr. Deodhar said at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN).

Treatment trials for nonradiologic axSpA (nr-axSpA) followed the development of diagnostic criteria by ASAS in 2009 (Ann. Rheum. Dis. 2009;68:777-83). On the basis of randomized controlled trials in nr-axSpA patients with adalimumab (ABILITY-1) and both nr-axSpA and axSpA patients with certolizumab pegol (AS001), both drugs were approved by the European Medicines Agency for the treatment nr-axSpA. The same evidence, reviewed by an FDA advisory committee in July 2013, produced rejections the following October.

The major problem, according to Dr. Deodhar’s account, was that the FDA found the ASAS diagnostic criteria "overly broad," creating a potential for some low-risk patients to be prescribed therapies in which a favorable benefit-to-risk ratio could not be ensured. But the decision also denied these biologics to patients who could benefit.

"Rheumatologists were put in a difficult position, inducing some to label these patients as having ankylosing spondylitis to obtain third-party approval for therapies they needed," Dr. Deodhar observed. Concerned that patients with significant disability were being denied effective therapies, leaders of both SPARTAN and ASAS are attempting to work with the FDA to define more acceptable criteria.

In a joint letter from SPARTAN and ASAS to the FDA in early 2014 requesting a meeting, the key issues outlined for discussion included the need to recognize axSpA in general and nr-axSpA specifically as pathologies associated with significant morbidity and for which there is an unmet need for therapies.

At the meeting, held in June, both of these points and several others regarding the clinical importance of nr-axSpA and axSpA were conceded by the FDA officials, according to Dr. Deodhar. He recounted that some rheumatologists on staff at the FDA continue to see patients and were empathetic about the unmet need for therapies even while expressing concern about overuse of biologics.

The solution, in the opinion of FDA regulators, as described by Dr. Deodhar, is a better set of sensitive and specific diagnostic criteria for nr-axSpA that can reliably define those patients who benefit from biologics or other therapies when compared with the current standard of care. This is a goal now being pursued by SPARTAN in collaboration with ASAS. The American College of Rheumatology (ACR) and the European League Against Rheumatism may also be invited to participate.

The acknowledgment by the FDA that nr-axSpA is a disease entity that is poorly treated with current options is an important first step in a process that Dr. Deodhar and others believe will eventually lead to approval of tumor necrosis factor inhibitors.

Asked for a comment, Dr. David Borenstein, clinical professor of rheumatology at George Washington University Medical Center, Washington, said he is confident that diagnostic criteria acceptable to professional rheumatology organizations and the FDA will eventually be created.

"There has been some dissension about the reproducibility of the current axSpA criteria and how they might be used effectively by nonspecialists," agreed Dr. Borenstein, who is a past president of the ACR. "We need to tighten the criteria to make sure we are all talking about the same problem."

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – For the first time, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis is preparing evidence-based treatment recommendations for the diagnosis and management of the comorbidities associated with psoriatic arthritis.

"I am really excited that we are taking the initiative to treat and manage the psoriatic arthritis [PsA] patient as a whole," reported Dr. Elaine Husni, director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. The guidelines are meant to be a "platform on which to raise awareness" and foster education.

An initial set of guidelines on comorbidities was drafted at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network (SPARTAN). Dr. Husni led the consensus group and fielded questions about key recommendations.

The first of these recommendations, which will undergo a process of discussion and review prior to formal adoption, states that all patients with PsA should be evaluated for cardiovascular (CV) disease. The consensus group labeled this recommendation "strong" even while conferring it with grade D evidence.

"The grade D was based on the fact that there are no outcomes data specifically in patients with psoriatic arthritis," observed Dr. Alexis R. Ogdie-Beatty, director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia. A member of the consensus group, Dr. Ogdie-Beatty suggested that benefit from CV screening is still a reasonable expectation "given the growing evidence that patients with PsA are at increased risk."

Similar "strong" recommendations but grade D evidence were given for screening for ophthalmic complications and inflammatory bowel disease. In these cases, there is good evidence for an association with PsA but limited evidence that screening will lead to improved outcome. The exception was obesity for which the group gave a B rating to the evidence for benefit from diagnosis and treatment.

Screening for diabetes was also included among recommendations, but it was given a "weak" rating and a grade D for supportive evidence.

Most of the other recommendations involved screening for various infections, such as hepatitis C virus (HCV), HIV, and tuberculosis, prior to initiating immunosuppressant therapies, particularly biologics. The level of evidence for these recommendations typically ranged between B and C even though all were given strong recommendations.

The consensus recommendations are not expected to include much detail about the specific management of comorbidities. The reason is concern about their applicability across various settings of care. It was thought that GRAPPA, as an international organization, should accommodate different types of practice. For example, the group cautioned against outlining steps of CV risk management, which may be managed by rheumatologists in some areas of the world but by specialists in others.

"We want to stay away from being minicardiologists," Dr. Husni explained. She indicated that the goal of the recommendations is to simply identify the specific types of comorbidity screening that should be considered "core recommendations" in the approach to PsA.

However, there is interest in creating a table regarding the use of specific medications for PsA treatment in the context of comorbidities. In a color-coded draft presented at the GRAPPA and SPARTAN meeting, some examples included caution in the use of NSAIDs in patients with CV disease, a need for monitoring when using cyclosporine in patients with chronic kidney disease, and a preference for etanercept over other tumor necrosis factor inhibitors in patients with HCV infection.

Overall, recommendations for comorbidities were identified as an important step in defining optimal care for PsA. According to Dr. Ogdie-Beatty, "the most important point may be to raise awareness." As these recommendations wend their way through an approval process at the organizational level, Dr. Ogdie-Beatty expressed hope that the final wording is specific enough to encourage attention to comorbidities without restricting a variety of valid approaches.

Dr. Husni reported a financial relationship with Celgene. Dr. Ogdie-Beatty had no potential conflicts of interest to report.

NEW YORK – For the first time, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis is preparing evidence-based treatment recommendations for the diagnosis and management of the comorbidities associated with psoriatic arthritis.

"I am really excited that we are taking the initiative to treat and manage the psoriatic arthritis [PsA] patient as a whole," reported Dr. Elaine Husni, director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. The guidelines are meant to be a "platform on which to raise awareness" and foster education.

An initial set of guidelines on comorbidities was drafted at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network (SPARTAN). Dr. Husni led the consensus group and fielded questions about key recommendations.

The first of these recommendations, which will undergo a process of discussion and review prior to formal adoption, states that all patients with PsA should be evaluated for cardiovascular (CV) disease. The consensus group labeled this recommendation "strong" even while conferring it with grade D evidence.

"The grade D was based on the fact that there are no outcomes data specifically in patients with psoriatic arthritis," observed Dr. Alexis R. Ogdie-Beatty, director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia. A member of the consensus group, Dr. Ogdie-Beatty suggested that benefit from CV screening is still a reasonable expectation "given the growing evidence that patients with PsA are at increased risk."

Similar "strong" recommendations but grade D evidence were given for screening for ophthalmic complications and inflammatory bowel disease. In these cases, there is good evidence for an association with PsA but limited evidence that screening will lead to improved outcome. The exception was obesity for which the group gave a B rating to the evidence for benefit from diagnosis and treatment.

Screening for diabetes was also included among recommendations, but it was given a "weak" rating and a grade D for supportive evidence.

Most of the other recommendations involved screening for various infections, such as hepatitis C virus (HCV), HIV, and tuberculosis, prior to initiating immunosuppressant therapies, particularly biologics. The level of evidence for these recommendations typically ranged between B and C even though all were given strong recommendations.

The consensus recommendations are not expected to include much detail about the specific management of comorbidities. The reason is concern about their applicability across various settings of care. It was thought that GRAPPA, as an international organization, should accommodate different types of practice. For example, the group cautioned against outlining steps of CV risk management, which may be managed by rheumatologists in some areas of the world but by specialists in others.

"We want to stay away from being minicardiologists," Dr. Husni explained. She indicated that the goal of the recommendations is to simply identify the specific types of comorbidity screening that should be considered "core recommendations" in the approach to PsA.

However, there is interest in creating a table regarding the use of specific medications for PsA treatment in the context of comorbidities. In a color-coded draft presented at the GRAPPA and SPARTAN meeting, some examples included caution in the use of NSAIDs in patients with CV disease, a need for monitoring when using cyclosporine in patients with chronic kidney disease, and a preference for etanercept over other tumor necrosis factor inhibitors in patients with HCV infection.

Overall, recommendations for comorbidities were identified as an important step in defining optimal care for PsA. According to Dr. Ogdie-Beatty, "the most important point may be to raise awareness." As these recommendations wend their way through an approval process at the organizational level, Dr. Ogdie-Beatty expressed hope that the final wording is specific enough to encourage attention to comorbidities without restricting a variety of valid approaches.

Dr. Husni reported a financial relationship with Celgene. Dr. Ogdie-Beatty had no potential conflicts of interest to report.

NEW YORK – For the first time, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis is preparing evidence-based treatment recommendations for the diagnosis and management of the comorbidities associated with psoriatic arthritis.

"I am really excited that we are taking the initiative to treat and manage the psoriatic arthritis [PsA] patient as a whole," reported Dr. Elaine Husni, director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. The guidelines are meant to be a "platform on which to raise awareness" and foster education.

An initial set of guidelines on comorbidities was drafted at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network (SPARTAN). Dr. Husni led the consensus group and fielded questions about key recommendations.

The first of these recommendations, which will undergo a process of discussion and review prior to formal adoption, states that all patients with PsA should be evaluated for cardiovascular (CV) disease. The consensus group labeled this recommendation "strong" even while conferring it with grade D evidence.

"The grade D was based on the fact that there are no outcomes data specifically in patients with psoriatic arthritis," observed Dr. Alexis R. Ogdie-Beatty, director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia. A member of the consensus group, Dr. Ogdie-Beatty suggested that benefit from CV screening is still a reasonable expectation "given the growing evidence that patients with PsA are at increased risk."

Similar "strong" recommendations but grade D evidence were given for screening for ophthalmic complications and inflammatory bowel disease. In these cases, there is good evidence for an association with PsA but limited evidence that screening will lead to improved outcome. The exception was obesity for which the group gave a B rating to the evidence for benefit from diagnosis and treatment.

Screening for diabetes was also included among recommendations, but it was given a "weak" rating and a grade D for supportive evidence.

Most of the other recommendations involved screening for various infections, such as hepatitis C virus (HCV), HIV, and tuberculosis, prior to initiating immunosuppressant therapies, particularly biologics. The level of evidence for these recommendations typically ranged between B and C even though all were given strong recommendations.

The consensus recommendations are not expected to include much detail about the specific management of comorbidities. The reason is concern about their applicability across various settings of care. It was thought that GRAPPA, as an international organization, should accommodate different types of practice. For example, the group cautioned against outlining steps of CV risk management, which may be managed by rheumatologists in some areas of the world but by specialists in others.

"We want to stay away from being minicardiologists," Dr. Husni explained. She indicated that the goal of the recommendations is to simply identify the specific types of comorbidity screening that should be considered "core recommendations" in the approach to PsA.

However, there is interest in creating a table regarding the use of specific medications for PsA treatment in the context of comorbidities. In a color-coded draft presented at the GRAPPA and SPARTAN meeting, some examples included caution in the use of NSAIDs in patients with CV disease, a need for monitoring when using cyclosporine in patients with chronic kidney disease, and a preference for etanercept over other tumor necrosis factor inhibitors in patients with HCV infection.

Overall, recommendations for comorbidities were identified as an important step in defining optimal care for PsA. According to Dr. Ogdie-Beatty, "the most important point may be to raise awareness." As these recommendations wend their way through an approval process at the organizational level, Dr. Ogdie-Beatty expressed hope that the final wording is specific enough to encourage attention to comorbidities without restricting a variety of valid approaches.

Dr. Husni reported a financial relationship with Celgene. Dr. Ogdie-Beatty had no potential conflicts of interest to report.

NEW YORK – Unexpectedly and conflicting with previous reports, a careful analysis of a relatively large series of patients with psoriatic arthritis mutilans found that most had axial involvement.

In a series of 56 patients with psoriatic arthritis (PsA) mutilans drawn from 610 consecutive patients with PsA, 65% had evidence of axial disease on the most recent radiograph. Of these, 57% had radiographic sacroiliitis, which was bilateral in 80%.

"This proportion far exceeds the typical 25% incidence of axial disease reported in the literature," according to Dr. Deepak Jadon, a specialist registrar in rheumatology at the Royal National Hospital for Rheumatic Diseases, Bath, England.

The proportion of confirmed PsA mutilans cases, at 9%, was also higher than the 5% typically reported, according to Dr. Jadon, who presented these findings at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network (SPARTAN). Referral to a specialty clinic may explain the higher rate, but PsA mutilans could only be ruled out, because of inadequate radiographs, in 483 of the 610 patients, so the actual proportion could be even higher.

In 35 of the patients with PsA mutilans, defined as osteolysis involving at least 50% of the visualized articular surface on both sides of the joints, serial radiographs confirmed that this disease is progressive. In this series, 37% of the patients had PsA mutilans at the time of the first radiograph, but the rest developed PsA mutilans over the course of follow-up.

Of this second group, 84% had received a disease-modifying antirheumatic drug (DMARD) prior to developing PsA mutilans, an observation that "suggests DMARDs may not prevent the onset of this condition," Dr. Jadon reported, cautioning that there are other potential explanations.

Using a random-effects model, "different patterns of progression were observed in the feet and hands," Dr. Jadon reported. In both groups, the most common pattern was an initial surge of activity followed by a tapering of rate of progression. However, a second surge of activity in the hands was not observed in the feet.

When compared to unaffected PsA patients, those with PsA mutilans were on average younger (33 vs. 40 years; P = .039) and more likely to have nail dystrophy (83% vs. 45%; P = .0002). The severity of nail dystrophy appeared to correlate with the severity of joint involvement.

The most commonly affected joints in this series were the metatarsophalangeal joint of the big toe, the proximal interphalangeal joint of the thumb, and the metacarpophalangeal joint of the index finger. While many patients had monoarticular involvement at the time of diagnosis, 80% of patients in this series had polyarticular disease on the most recent radiograph.

Not surprisingly, functional limitations were significantly greater for patients with PsA mutilans on standardized health assessment questionnaire (HAQ) when compared with patients with PsA (P = .048). The differences involved functions affecting both the hands, such as those relevant to grip strength, and the feet.

Data from this series did not provide any insight on treatment efficacy. Biologic use in those with serial radiographs, which included a sizeable number of patients managed before the biologic era, was too infrequent to infer effect on disease progression. However, the frequent exposure to DMARDs in patients with documented progression suggests benefits may be limited.

Dr. Jadon suggested that prospective data for PsA mutilans, which is widely regarded as the least common but most severe form of PsA, are now needed to determine which treatments have the greatest potential to improve long-term outcome.

Dr. Jadon reported no potential conflicts of interest.

NEW YORK – Unexpectedly and conflicting with previous reports, a careful analysis of a relatively large series of patients with psoriatic arthritis mutilans found that most had axial involvement.

In a series of 56 patients with psoriatic arthritis (PsA) mutilans drawn from 610 consecutive patients with PsA, 65% had evidence of axial disease on the most recent radiograph. Of these, 57% had radiographic sacroiliitis, which was bilateral in 80%.

"This proportion far exceeds the typical 25% incidence of axial disease reported in the literature," according to Dr. Deepak Jadon, a specialist registrar in rheumatology at the Royal National Hospital for Rheumatic Diseases, Bath, England.

The proportion of confirmed PsA mutilans cases, at 9%, was also higher than the 5% typically reported, according to Dr. Jadon, who presented these findings at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network (SPARTAN). Referral to a specialty clinic may explain the higher rate, but PsA mutilans could only be ruled out, because of inadequate radiographs, in 483 of the 610 patients, so the actual proportion could be even higher.

In 35 of the patients with PsA mutilans, defined as osteolysis involving at least 50% of the visualized articular surface on both sides of the joints, serial radiographs confirmed that this disease is progressive. In this series, 37% of the patients had PsA mutilans at the time of the first radiograph, but the rest developed PsA mutilans over the course of follow-up.

Of this second group, 84% had received a disease-modifying antirheumatic drug (DMARD) prior to developing PsA mutilans, an observation that "suggests DMARDs may not prevent the onset of this condition," Dr. Jadon reported, cautioning that there are other potential explanations.

Using a random-effects model, "different patterns of progression were observed in the feet and hands," Dr. Jadon reported. In both groups, the most common pattern was an initial surge of activity followed by a tapering of rate of progression. However, a second surge of activity in the hands was not observed in the feet.

When compared to unaffected PsA patients, those with PsA mutilans were on average younger (33 vs. 40 years; P = .039) and more likely to have nail dystrophy (83% vs. 45%; P = .0002). The severity of nail dystrophy appeared to correlate with the severity of joint involvement.

The most commonly affected joints in this series were the metatarsophalangeal joint of the big toe, the proximal interphalangeal joint of the thumb, and the metacarpophalangeal joint of the index finger. While many patients had monoarticular involvement at the time of diagnosis, 80% of patients in this series had polyarticular disease on the most recent radiograph.

Not surprisingly, functional limitations were significantly greater for patients with PsA mutilans on standardized health assessment questionnaire (HAQ) when compared with patients with PsA (P = .048). The differences involved functions affecting both the hands, such as those relevant to grip strength, and the feet.

Data from this series did not provide any insight on treatment efficacy. Biologic use in those with serial radiographs, which included a sizeable number of patients managed before the biologic era, was too infrequent to infer effect on disease progression. However, the frequent exposure to DMARDs in patients with documented progression suggests benefits may be limited.

Dr. Jadon suggested that prospective data for PsA mutilans, which is widely regarded as the least common but most severe form of PsA, are now needed to determine which treatments have the greatest potential to improve long-term outcome.

Dr. Jadon reported no potential conflicts of interest.

NEW YORK – Unexpectedly and conflicting with previous reports, a careful analysis of a relatively large series of patients with psoriatic arthritis mutilans found that most had axial involvement.

In a series of 56 patients with psoriatic arthritis (PsA) mutilans drawn from 610 consecutive patients with PsA, 65% had evidence of axial disease on the most recent radiograph. Of these, 57% had radiographic sacroiliitis, which was bilateral in 80%.

"This proportion far exceeds the typical 25% incidence of axial disease reported in the literature," according to Dr. Deepak Jadon, a specialist registrar in rheumatology at the Royal National Hospital for Rheumatic Diseases, Bath, England.

The proportion of confirmed PsA mutilans cases, at 9%, was also higher than the 5% typically reported, according to Dr. Jadon, who presented these findings at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network (SPARTAN). Referral to a specialty clinic may explain the higher rate, but PsA mutilans could only be ruled out, because of inadequate radiographs, in 483 of the 610 patients, so the actual proportion could be even higher.

In 35 of the patients with PsA mutilans, defined as osteolysis involving at least 50% of the visualized articular surface on both sides of the joints, serial radiographs confirmed that this disease is progressive. In this series, 37% of the patients had PsA mutilans at the time of the first radiograph, but the rest developed PsA mutilans over the course of follow-up.

Of this second group, 84% had received a disease-modifying antirheumatic drug (DMARD) prior to developing PsA mutilans, an observation that "suggests DMARDs may not prevent the onset of this condition," Dr. Jadon reported, cautioning that there are other potential explanations.

Using a random-effects model, "different patterns of progression were observed in the feet and hands," Dr. Jadon reported. In both groups, the most common pattern was an initial surge of activity followed by a tapering of rate of progression. However, a second surge of activity in the hands was not observed in the feet.

When compared to unaffected PsA patients, those with PsA mutilans were on average younger (33 vs. 40 years; P = .039) and more likely to have nail dystrophy (83% vs. 45%; P = .0002). The severity of nail dystrophy appeared to correlate with the severity of joint involvement.

The most commonly affected joints in this series were the metatarsophalangeal joint of the big toe, the proximal interphalangeal joint of the thumb, and the metacarpophalangeal joint of the index finger. While many patients had monoarticular involvement at the time of diagnosis, 80% of patients in this series had polyarticular disease on the most recent radiograph.

Not surprisingly, functional limitations were significantly greater for patients with PsA mutilans on standardized health assessment questionnaire (HAQ) when compared with patients with PsA (P = .048). The differences involved functions affecting both the hands, such as those relevant to grip strength, and the feet.

Data from this series did not provide any insight on treatment efficacy. Biologic use in those with serial radiographs, which included a sizeable number of patients managed before the biologic era, was too infrequent to infer effect on disease progression. However, the frequent exposure to DMARDs in patients with documented progression suggests benefits may be limited.

Dr. Jadon suggested that prospective data for PsA mutilans, which is widely regarded as the least common but most severe form of PsA, are now needed to determine which treatments have the greatest potential to improve long-term outcome.

Dr. Jadon reported no potential conflicts of interest.

NEW YORK – Improvements in clinical trial design for psoriasis, psoriatic arthritis, and other inflammatory diseases are being credited to a decision to enlist patients as full partners, not just advisors or consultants, in research initiatives.

"Rheumatologists, I think, have been leaders is recognizing that patients can bring an expertise to clinical research that is unique and ensure that study endpoints are relevant to outcomes important to them," reported Dr. William Tillett, a research fellow in the department of rheumatology at the Royal National Hospital for Rheumatic Diseases in Bath, England.

The value of patient research partners (PRP) was a recurring theme at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network. GRAPPA, in particular, has been fostering research collaborations with patients since 2006.

"It has been an evolution. Patients were initially enlisted to sit in when trial designs were being discussed. Now, we are talking about full partnership so that they are involved at the inception with equal partnership that includes veto power and author credit," Dr. Tillett explained.

At the GRAPPA meeting, an afternoon symposium was devoted to optimal strategies for fostering collaboration with PRPs, which builds on work already initiated with a group called Patient Involvement for Outcome Measures in PsA (PIOMPsA). In turn, PIOMPsA, formed 2 years ago, was largely modeled on PRP initiatives led by OMERACT (Outcomes Measurement in Rheumatology).

"OMERACT has been involving patients in clinical research design for about 10 years," reported Dr. Philip J. Mease, director of rheumatology research at Swedish Medical Center, Seattle. "The idea of making patients full-blown partners is more recent, but I think there is increasing appreciation for what the right patients can contribute to improve study design."

The initiatives are spreading through rheumatology and other inflammatory diseases. At the GRAPPA meeting, updates on patient initiatives to influence clinical research were presented not only from the work of PIOMPsA and OMERACT but also from the International Dermatology Outcomes Measures (IDEOM) consortium. Created in collaboration with the National Psoriasis Foundation (NPF), IDEOM is bringing clinicians and patients together to define standard outcome measures.

"There are no really good measures to evaluate relative severity of psoriasis from the patient’s perspective," reported Dr. Alice Gottlieb, professor of dermatology at Tufts Medical Center, Boston. Tools traditionally used in clinical trials, such as the Psoriasis Area Severity Index (PASI) "are not practical in the clinic" and do not necessarily reflect the impact of psoriasis on quality of life when used as a study endpoint, she said.

PIOMPsA has now conducted several meetings, including one held in conjunction with OMERACT in Budapest, Hungary, in early May 2014. Like IDEOM, PIOMPsA has been focused on developing consensus on core symptoms of its target inflammatory disease. This is critical because the ability of clinical trials to generate relevant data is dependent on first defining meaningful endpoints, according to Dr. Tillett, who presented the PIOMPsA deliberations at the GRAPPA meeting.

In Budapest, for example, a vote was taken on whether to add fatigue to a list of core symptoms for PsA that includes impaired physical function, skin lesions, and joint pain. Fatigue was added to the list by a vote in which 70% supported it as a core PsA symptom, said Dr. Tillett, who recently published on the goals and underlying concepts of PIOMPsA (Curr. Rheumatol. Rep. 2014;16:418).

According to Dr. Tillett and Dr. Mease, PRPs are an answer to the repeatedly reported disconnect between physicians and patients in rating disease severity. By involving patients with interest in clinical research and collaborative skills, treatment trials have the potential to generate data more useful to practical patient management.

"It will be very difficult to show objectively that patient-aided trial design leads to better studies, but this is a reasonable expectation. I think that the contributions we have already seen from these collaborations bear this out," said Dr. Tillett, who expects the concept to spread to other fields of medicine.

Dr. Tillett reported financial relationships with AbbVie and Amgen. Dr. Mease reported financial relationships with AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen Pharmaceuticals, Lilly, Merck & Co, Novartis, Pfizer, UCB Pharma, and Vertex. Dr. Gottlieb reported financial relationships with Abbott, Actelion, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Novo Nordisk, Teva, and UCB.

NEW YORK – Improvements in clinical trial design for psoriasis, psoriatic arthritis, and other inflammatory diseases are being credited to a decision to enlist patients as full partners, not just advisors or consultants, in research initiatives.

"Rheumatologists, I think, have been leaders is recognizing that patients can bring an expertise to clinical research that is unique and ensure that study endpoints are relevant to outcomes important to them," reported Dr. William Tillett, a research fellow in the department of rheumatology at the Royal National Hospital for Rheumatic Diseases in Bath, England.

The value of patient research partners (PRP) was a recurring theme at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network. GRAPPA, in particular, has been fostering research collaborations with patients since 2006.

"It has been an evolution. Patients were initially enlisted to sit in when trial designs were being discussed. Now, we are talking about full partnership so that they are involved at the inception with equal partnership that includes veto power and author credit," Dr. Tillett explained.

At the GRAPPA meeting, an afternoon symposium was devoted to optimal strategies for fostering collaboration with PRPs, which builds on work already initiated with a group called Patient Involvement for Outcome Measures in PsA (PIOMPsA). In turn, PIOMPsA, formed 2 years ago, was largely modeled on PRP initiatives led by OMERACT (Outcomes Measurement in Rheumatology).

"OMERACT has been involving patients in clinical research design for about 10 years," reported Dr. Philip J. Mease, director of rheumatology research at Swedish Medical Center, Seattle. "The idea of making patients full-blown partners is more recent, but I think there is increasing appreciation for what the right patients can contribute to improve study design."

The initiatives are spreading through rheumatology and other inflammatory diseases. At the GRAPPA meeting, updates on patient initiatives to influence clinical research were presented not only from the work of PIOMPsA and OMERACT but also from the International Dermatology Outcomes Measures (IDEOM) consortium. Created in collaboration with the National Psoriasis Foundation (NPF), IDEOM is bringing clinicians and patients together to define standard outcome measures.

"There are no really good measures to evaluate relative severity of psoriasis from the patient’s perspective," reported Dr. Alice Gottlieb, professor of dermatology at Tufts Medical Center, Boston. Tools traditionally used in clinical trials, such as the Psoriasis Area Severity Index (PASI) "are not practical in the clinic" and do not necessarily reflect the impact of psoriasis on quality of life when used as a study endpoint, she said.

PIOMPsA has now conducted several meetings, including one held in conjunction with OMERACT in Budapest, Hungary, in early May 2014. Like IDEOM, PIOMPsA has been focused on developing consensus on core symptoms of its target inflammatory disease. This is critical because the ability of clinical trials to generate relevant data is dependent on first defining meaningful endpoints, according to Dr. Tillett, who presented the PIOMPsA deliberations at the GRAPPA meeting.

In Budapest, for example, a vote was taken on whether to add fatigue to a list of core symptoms for PsA that includes impaired physical function, skin lesions, and joint pain. Fatigue was added to the list by a vote in which 70% supported it as a core PsA symptom, said Dr. Tillett, who recently published on the goals and underlying concepts of PIOMPsA (Curr. Rheumatol. Rep. 2014;16:418).

According to Dr. Tillett and Dr. Mease, PRPs are an answer to the repeatedly reported disconnect between physicians and patients in rating disease severity. By involving patients with interest in clinical research and collaborative skills, treatment trials have the potential to generate data more useful to practical patient management.

"It will be very difficult to show objectively that patient-aided trial design leads to better studies, but this is a reasonable expectation. I think that the contributions we have already seen from these collaborations bear this out," said Dr. Tillett, who expects the concept to spread to other fields of medicine.

Dr. Tillett reported financial relationships with AbbVie and Amgen. Dr. Mease reported financial relationships with AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen Pharmaceuticals, Lilly, Merck & Co, Novartis, Pfizer, UCB Pharma, and Vertex. Dr. Gottlieb reported financial relationships with Abbott, Actelion, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Novo Nordisk, Teva, and UCB.

NEW YORK – Improvements in clinical trial design for psoriasis, psoriatic arthritis, and other inflammatory diseases are being credited to a decision to enlist patients as full partners, not just advisors or consultants, in research initiatives.

"Rheumatologists, I think, have been leaders is recognizing that patients can bring an expertise to clinical research that is unique and ensure that study endpoints are relevant to outcomes important to them," reported Dr. William Tillett, a research fellow in the department of rheumatology at the Royal National Hospital for Rheumatic Diseases in Bath, England.

The value of patient research partners (PRP) was a recurring theme at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network. GRAPPA, in particular, has been fostering research collaborations with patients since 2006.

"It has been an evolution. Patients were initially enlisted to sit in when trial designs were being discussed. Now, we are talking about full partnership so that they are involved at the inception with equal partnership that includes veto power and author credit," Dr. Tillett explained.

At the GRAPPA meeting, an afternoon symposium was devoted to optimal strategies for fostering collaboration with PRPs, which builds on work already initiated with a group called Patient Involvement for Outcome Measures in PsA (PIOMPsA). In turn, PIOMPsA, formed 2 years ago, was largely modeled on PRP initiatives led by OMERACT (Outcomes Measurement in Rheumatology).

"OMERACT has been involving patients in clinical research design for about 10 years," reported Dr. Philip J. Mease, director of rheumatology research at Swedish Medical Center, Seattle. "The idea of making patients full-blown partners is more recent, but I think there is increasing appreciation for what the right patients can contribute to improve study design."

The initiatives are spreading through rheumatology and other inflammatory diseases. At the GRAPPA meeting, updates on patient initiatives to influence clinical research were presented not only from the work of PIOMPsA and OMERACT but also from the International Dermatology Outcomes Measures (IDEOM) consortium. Created in collaboration with the National Psoriasis Foundation (NPF), IDEOM is bringing clinicians and patients together to define standard outcome measures.

"There are no really good measures to evaluate relative severity of psoriasis from the patient’s perspective," reported Dr. Alice Gottlieb, professor of dermatology at Tufts Medical Center, Boston. Tools traditionally used in clinical trials, such as the Psoriasis Area Severity Index (PASI) "are not practical in the clinic" and do not necessarily reflect the impact of psoriasis on quality of life when used as a study endpoint, she said.

PIOMPsA has now conducted several meetings, including one held in conjunction with OMERACT in Budapest, Hungary, in early May 2014. Like IDEOM, PIOMPsA has been focused on developing consensus on core symptoms of its target inflammatory disease. This is critical because the ability of clinical trials to generate relevant data is dependent on first defining meaningful endpoints, according to Dr. Tillett, who presented the PIOMPsA deliberations at the GRAPPA meeting.

In Budapest, for example, a vote was taken on whether to add fatigue to a list of core symptoms for PsA that includes impaired physical function, skin lesions, and joint pain. Fatigue was added to the list by a vote in which 70% supported it as a core PsA symptom, said Dr. Tillett, who recently published on the goals and underlying concepts of PIOMPsA (Curr. Rheumatol. Rep. 2014;16:418).

According to Dr. Tillett and Dr. Mease, PRPs are an answer to the repeatedly reported disconnect between physicians and patients in rating disease severity. By involving patients with interest in clinical research and collaborative skills, treatment trials have the potential to generate data more useful to practical patient management.

"It will be very difficult to show objectively that patient-aided trial design leads to better studies, but this is a reasonable expectation. I think that the contributions we have already seen from these collaborations bear this out," said Dr. Tillett, who expects the concept to spread to other fields of medicine.

Dr. Tillett reported financial relationships with AbbVie and Amgen. Dr. Mease reported financial relationships with AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen Pharmaceuticals, Lilly, Merck & Co, Novartis, Pfizer, UCB Pharma, and Vertex. Dr. Gottlieb reported financial relationships with Abbott, Actelion, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Novo Nordisk, Teva, and UCB.

NEW YORK – For the skin component of psoriatic arthritis, consensus about how high to set the bar for disease control continues to elude experts, judging from a debate about the value of "clear" or "almost clear" as the most acceptable treatment endpoints.

Current therapies in psoriatic arthritis (PsA) are sufficiently effective to support a treat-to-target approach for both skin lesions and joint inflammation, but there is lack of consensus about which metrics should be employed to define any specific target for skin lesions, according to Dr. Joel Gelfand, medical director of the clinical studies unit in the department of dermatology at the University of Pennsylvania, Philadelphia. He noted that even if the goal is the absence of skin involvement, no one agrees on what method should be used to document this endpoint.

"No one in clinical practice uses PASI," maintained Dr. Gelfand, referring to the Psoriasis and Area and Severity Index, which is one of the most widely accepted standards for judging efficacy in treatment trials. Speaking at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network, Dr. Gelfand said most objective scoring systems, such as PASI, are too labor intensive. Clinicians tend to use their own system for documenting relative control of skin lesions in the medical record.

Evaluating disease control without applying a reproducible, broadly used metric has numerous potential problems, according to Dr. Gelfand. Most importantly, it prevents objective evaluation of whether treatment targets are being met. This obscures efforts to document benefit relative to either clinical goals or optimal care. Dr. Gelfand made the analogy to the treatment goals created for blood pressure, blood glucose, or cholesterol, where the targets are clear and a change in treatment is warranted if the target is not reached.

This point of view resonated with the audience of dermatologists, rheumatologists, and PsA patients attending the meeting. In an electronic audience poll, there was nearly 100% agreement that a treat-to-target approach is appropriate for skin lesions but no strong consensus on what the target should be. In the poll attempting to define consensus, 32% agreed with a target of less than 3% body surface area (BSA) while 48% agreed the BSA target should be less than 1%. It is notable that dermatologists were more likely to accept a less rigorous BSA than rheumatologists. The majority of patients agreed the target should be less than 1% BSA, although this group represented less than 10% of the audience.

Not surprisingly, health-related quality of life studies show measurable differences between "clear" and "almost clear" skin lesions in PsA patients whether measured by PASI, BSA, or other measures, according to Dr. Gelfand, but he cautioned that it is important to be realistic about goals. He suggested that a target that exposes patients to unacceptable side effects is the wrong target, and this may be the source of dissension among experts.

Asked for a comment, Dr. Wolf-Henning Boehncke, professor and chair of the department of dermatology at the University of Geneva agreed in principle with the treat-to-target approach. However, Dr. Boehncke, who is the current president of GRAPPA, also emphasized simple and practical assessment tools and achievable endpoints.

"We must define targets that are reasonable," Dr. Boehncke said. While complex patient assessment tools are not likely to be widely used by clinicians, unrealistic targets can be counterproductive if they are not considered in the overall context of tolerability and patient satisfaction.

Dr. Gelfand has or has had financial relationships with AbbVie, Amgen, Celgene, Eli Lilly, Genentech, Janssen, Merck, Novartis, and Pfizer.

NEW YORK – For the skin component of psoriatic arthritis, consensus about how high to set the bar for disease control continues to elude experts, judging from a debate about the value of "clear" or "almost clear" as the most acceptable treatment endpoints.

Current therapies in psoriatic arthritis (PsA) are sufficiently effective to support a treat-to-target approach for both skin lesions and joint inflammation, but there is lack of consensus about which metrics should be employed to define any specific target for skin lesions, according to Dr. Joel Gelfand, medical director of the clinical studies unit in the department of dermatology at the University of Pennsylvania, Philadelphia. He noted that even if the goal is the absence of skin involvement, no one agrees on what method should be used to document this endpoint.

"No one in clinical practice uses PASI," maintained Dr. Gelfand, referring to the Psoriasis and Area and Severity Index, which is one of the most widely accepted standards for judging efficacy in treatment trials. Speaking at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network, Dr. Gelfand said most objective scoring systems, such as PASI, are too labor intensive. Clinicians tend to use their own system for documenting relative control of skin lesions in the medical record.

Evaluating disease control without applying a reproducible, broadly used metric has numerous potential problems, according to Dr. Gelfand. Most importantly, it prevents objective evaluation of whether treatment targets are being met. This obscures efforts to document benefit relative to either clinical goals or optimal care. Dr. Gelfand made the analogy to the treatment goals created for blood pressure, blood glucose, or cholesterol, where the targets are clear and a change in treatment is warranted if the target is not reached.

This point of view resonated with the audience of dermatologists, rheumatologists, and PsA patients attending the meeting. In an electronic audience poll, there was nearly 100% agreement that a treat-to-target approach is appropriate for skin lesions but no strong consensus on what the target should be. In the poll attempting to define consensus, 32% agreed with a target of less than 3% body surface area (BSA) while 48% agreed the BSA target should be less than 1%. It is notable that dermatologists were more likely to accept a less rigorous BSA than rheumatologists. The majority of patients agreed the target should be less than 1% BSA, although this group represented less than 10% of the audience.

Not surprisingly, health-related quality of life studies show measurable differences between "clear" and "almost clear" skin lesions in PsA patients whether measured by PASI, BSA, or other measures, according to Dr. Gelfand, but he cautioned that it is important to be realistic about goals. He suggested that a target that exposes patients to unacceptable side effects is the wrong target, and this may be the source of dissension among experts.

Asked for a comment, Dr. Wolf-Henning Boehncke, professor and chair of the department of dermatology at the University of Geneva agreed in principle with the treat-to-target approach. However, Dr. Boehncke, who is the current president of GRAPPA, also emphasized simple and practical assessment tools and achievable endpoints.

"We must define targets that are reasonable," Dr. Boehncke said. While complex patient assessment tools are not likely to be widely used by clinicians, unrealistic targets can be counterproductive if they are not considered in the overall context of tolerability and patient satisfaction.

Dr. Gelfand has or has had financial relationships with AbbVie, Amgen, Celgene, Eli Lilly, Genentech, Janssen, Merck, Novartis, and Pfizer.

NEW YORK – For the skin component of psoriatic arthritis, consensus about how high to set the bar for disease control continues to elude experts, judging from a debate about the value of "clear" or "almost clear" as the most acceptable treatment endpoints.

Current therapies in psoriatic arthritis (PsA) are sufficiently effective to support a treat-to-target approach for both skin lesions and joint inflammation, but there is lack of consensus about which metrics should be employed to define any specific target for skin lesions, according to Dr. Joel Gelfand, medical director of the clinical studies unit in the department of dermatology at the University of Pennsylvania, Philadelphia. He noted that even if the goal is the absence of skin involvement, no one agrees on what method should be used to document this endpoint.

"No one in clinical practice uses PASI," maintained Dr. Gelfand, referring to the Psoriasis and Area and Severity Index, which is one of the most widely accepted standards for judging efficacy in treatment trials. Speaking at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Spondyloarthritis Research & Treatment Network, Dr. Gelfand said most objective scoring systems, such as PASI, are too labor intensive. Clinicians tend to use their own system for documenting relative control of skin lesions in the medical record.

Evaluating disease control without applying a reproducible, broadly used metric has numerous potential problems, according to Dr. Gelfand. Most importantly, it prevents objective evaluation of whether treatment targets are being met. This obscures efforts to document benefit relative to either clinical goals or optimal care. Dr. Gelfand made the analogy to the treatment goals created for blood pressure, blood glucose, or cholesterol, where the targets are clear and a change in treatment is warranted if the target is not reached.

This point of view resonated with the audience of dermatologists, rheumatologists, and PsA patients attending the meeting. In an electronic audience poll, there was nearly 100% agreement that a treat-to-target approach is appropriate for skin lesions but no strong consensus on what the target should be. In the poll attempting to define consensus, 32% agreed with a target of less than 3% body surface area (BSA) while 48% agreed the BSA target should be less than 1%. It is notable that dermatologists were more likely to accept a less rigorous BSA than rheumatologists. The majority of patients agreed the target should be less than 1% BSA, although this group represented less than 10% of the audience.

Not surprisingly, health-related quality of life studies show measurable differences between "clear" and "almost clear" skin lesions in PsA patients whether measured by PASI, BSA, or other measures, according to Dr. Gelfand, but he cautioned that it is important to be realistic about goals. He suggested that a target that exposes patients to unacceptable side effects is the wrong target, and this may be the source of dissension among experts.

Asked for a comment, Dr. Wolf-Henning Boehncke, professor and chair of the department of dermatology at the University of Geneva agreed in principle with the treat-to-target approach. However, Dr. Boehncke, who is the current president of GRAPPA, also emphasized simple and practical assessment tools and achievable endpoints.

"We must define targets that are reasonable," Dr. Boehncke said. While complex patient assessment tools are not likely to be widely used by clinicians, unrealistic targets can be counterproductive if they are not considered in the overall context of tolerability and patient satisfaction.

Dr. Gelfand has or has had financial relationships with AbbVie, Amgen, Celgene, Eli Lilly, Genentech, Janssen, Merck, Novartis, and Pfizer.

At least two-thirds of adults with plaque psoriasis treated with the fully human anti-interleukin-17A monoclonal antibody secukinumab achieved PASI 75 at 12 weeks in two related randomized phase III trials. The findings were reported online July 9 in the New England Journal of Medicine.

In the ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) trial, a multicenter, double-blind study involving 738 patients, the proportions of patients who achieved a 75% or greater reduction in Psoriasis Area and Severity Index (PASI 75) score at 12 weeks were 81.6%, 71.6%, and 4.5% with 300 mg of secukinumab, 150 mg of secukinumab, and placebo, respectively.

In the FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens) study, a multicenter, double-blind, active-controlled study involving 1,306 patients, the proportions meeting PASI 75 were 77.1% and 67% for 300 and 150 mg, respectively, compared with 44% for etanercept and 4.9% for placebo.

The difference between each secukinumab dose and its comparators was statistically significant in both studies, Dr. Richard G. Langley of Dalhousie University, Halifax, N.S., Dr. Boni Elewski of the University of Alabama, Birmingham, and their colleagues reported on behalf of the ERASURE and FIXTURE Study Groups.

The investigators also found that the proportions of patients with a response of 0 or 1 on the modified investigator’s global assessment at 12 weeks were 65.3%, 51.2%, and 2.4% for the 300- and 150-mg secukinumab doses and placebo, respectively, in ERASURE; and 62.5% and 51.1% for the 300- and 150-mg doses, 27.2% for etanercept, and 2.8% for placebo in FIXTURE (N. Engl. J. Med. 2014 July 9 [doi: 10.1056/NE/NEJMoa314258]).

The differences between each secukinumab dose and its comparators were significant for this measure as well, the investigators reported.

Secukinumab at the 300- and 150-mg doses in both ERASURE and FIXTURE was also superior to placebo (and in FIXTURE, superior to etanercept) for all secondary efficacy endpoints, including PASI 90 and PASI 100 response at week 12; patient reports of itching, pain, and scaling on the Psoriasis Symptom Diary at week 12; and Dermatology Life Quality Index scores.

Both ERASURE and FIXTURE were designed to evaluate the safety of secukinumab as induction therapy with assessment at week 12, and as maintenance therapy with assessment at week 52. Subjects were aged 18 years or older with poorly controlled, moderate to severe plaque psoriasis that had been diagnosed at least 6 months prior, and with a PASI score of 12 or higher, a modified investigator’s global assessment score of 3 or 4, and involvement of 10% or more of their body surface area.

ERASURE was conducted from June 2011 to April 2013 at 88 sites worldwide, and FIXTURE was conducted from June 2011 to June 2013 at 231 sites. Patients in the 300-mg groups received two 150-mg subcutaneous injections of secukinumab, and those in the 150-mg group received one 150-mg injection of secukinumab, and one placebo injection. Etanercept was given at a dose of 50 mg administered subcutaneously twice weekly from baseline until week 12, and then once weekly through week 51.

Adverse events were more common in patients treated with secukinumab in ERASURE; 55% of patients in the 300-mg group, 60.4% in the 150-mg group, and 47% in the placebo group experienced at least one adverse event during the induction period, and 29.4%, 26.9%, and 16.2% in those groups, respectively, experienced infections and/or infestations. The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection.

The incidence of adverse events in FIXTURE was similar in those receiving secukinumab and etanercept, and was greater in both groups than in the placebo group. Infections and infestations occurred in 26.7%, 30.9%, 24.5%, and 19.3% of those receiving 300 mg of secukinumab, 150 mg of secukinumab, etanercept, and placebo, respectively. However, candida infections were more common with secukinumab than with etanercept (4.7%, 2.3%, and 1.2% of patients in the 300- and 150-mg secukinumab groups and the etanercept group, respectively, had candida infections). All candida infections in the secukinumab group were mild or moderate, and two of four infections in the etanercept group were severe.

Grade 3 neutropenia occurred in nine patients receiving secukinumab and in no patients receiving etanercept.

"The results of these phase 3 studies validate interleukin-17A as an important therapeutic target in moderate to severe plaque psoriasis, confirming earlier findings from basic research and phase 2 trials of secukinumab that suggested that interleukin-17A plays a role in the pathogenesis of psoriasis," the investigators said.

Interleukin-17A plays a key role in host defense, specifically in mucocutaneous microbial surveillance, they added.

"Continued vigilance with respect to the potential for candida infection will be necessary for interleukin-17A inhibitors. Neutropenia may also be of potential concern because of the reported role of interleukin-17A in the stimulation of granulopoiesis and neutrophil trafficking," they noted.

A limitation of both ERASURE and FIXTURE was that few patients continued to receive placebo after week 12, thus limiting the comparisons with the placebo group during the maintenance periods. Also, the study populations may have been too small to detect rare adverse events, the authors wrote, noting that extension studies to evaluate long-term efficacy are ongoing.

ERASURE and FIXTURE were supported by Novartis Pharmaceuticals. Dr. Langley reported no conflicts related to these studies. Dr. Elewski disclosed funding from Novartis during the study period.

At least two-thirds of adults with plaque psoriasis treated with the fully human anti-interleukin-17A monoclonal antibody secukinumab achieved PASI 75 at 12 weeks in two related randomized phase III trials. The findings were reported online July 9 in the New England Journal of Medicine.

In the ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) trial, a multicenter, double-blind study involving 738 patients, the proportions of patients who achieved a 75% or greater reduction in Psoriasis Area and Severity Index (PASI 75) score at 12 weeks were 81.6%, 71.6%, and 4.5% with 300 mg of secukinumab, 150 mg of secukinumab, and placebo, respectively.

In the FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens) study, a multicenter, double-blind, active-controlled study involving 1,306 patients, the proportions meeting PASI 75 were 77.1% and 67% for 300 and 150 mg, respectively, compared with 44% for etanercept and 4.9% for placebo.

The difference between each secukinumab dose and its comparators was statistically significant in both studies, Dr. Richard G. Langley of Dalhousie University, Halifax, N.S., Dr. Boni Elewski of the University of Alabama, Birmingham, and their colleagues reported on behalf of the ERASURE and FIXTURE Study Groups.

The investigators also found that the proportions of patients with a response of 0 or 1 on the modified investigator’s global assessment at 12 weeks were 65.3%, 51.2%, and 2.4% for the 300- and 150-mg secukinumab doses and placebo, respectively, in ERASURE; and 62.5% and 51.1% for the 300- and 150-mg doses, 27.2% for etanercept, and 2.8% for placebo in FIXTURE (N. Engl. J. Med. 2014 July 9 [doi: 10.1056/NE/NEJMoa314258]).

The differences between each secukinumab dose and its comparators were significant for this measure as well, the investigators reported.

Secukinumab at the 300- and 150-mg doses in both ERASURE and FIXTURE was also superior to placebo (and in FIXTURE, superior to etanercept) for all secondary efficacy endpoints, including PASI 90 and PASI 100 response at week 12; patient reports of itching, pain, and scaling on the Psoriasis Symptom Diary at week 12; and Dermatology Life Quality Index scores.

Both ERASURE and FIXTURE were designed to evaluate the safety of secukinumab as induction therapy with assessment at week 12, and as maintenance therapy with assessment at week 52. Subjects were aged 18 years or older with poorly controlled, moderate to severe plaque psoriasis that had been diagnosed at least 6 months prior, and with a PASI score of 12 or higher, a modified investigator’s global assessment score of 3 or 4, and involvement of 10% or more of their body surface area.

ERASURE was conducted from June 2011 to April 2013 at 88 sites worldwide, and FIXTURE was conducted from June 2011 to June 2013 at 231 sites. Patients in the 300-mg groups received two 150-mg subcutaneous injections of secukinumab, and those in the 150-mg group received one 150-mg injection of secukinumab, and one placebo injection. Etanercept was given at a dose of 50 mg administered subcutaneously twice weekly from baseline until week 12, and then once weekly through week 51.

Adverse events were more common in patients treated with secukinumab in ERASURE; 55% of patients in the 300-mg group, 60.4% in the 150-mg group, and 47% in the placebo group experienced at least one adverse event during the induction period, and 29.4%, 26.9%, and 16.2% in those groups, respectively, experienced infections and/or infestations. The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection.

The incidence of adverse events in FIXTURE was similar in those receiving secukinumab and etanercept, and was greater in both groups than in the placebo group. Infections and infestations occurred in 26.7%, 30.9%, 24.5%, and 19.3% of those receiving 300 mg of secukinumab, 150 mg of secukinumab, etanercept, and placebo, respectively. However, candida infections were more common with secukinumab than with etanercept (4.7%, 2.3%, and 1.2% of patients in the 300- and 150-mg secukinumab groups and the etanercept group, respectively, had candida infections). All candida infections in the secukinumab group were mild or moderate, and two of four infections in the etanercept group were severe.

Grade 3 neutropenia occurred in nine patients receiving secukinumab and in no patients receiving etanercept.

"The results of these phase 3 studies validate interleukin-17A as an important therapeutic target in moderate to severe plaque psoriasis, confirming earlier findings from basic research and phase 2 trials of secukinumab that suggested that interleukin-17A plays a role in the pathogenesis of psoriasis," the investigators said.

Interleukin-17A plays a key role in host defense, specifically in mucocutaneous microbial surveillance, they added.

"Continued vigilance with respect to the potential for candida infection will be necessary for interleukin-17A inhibitors. Neutropenia may also be of potential concern because of the reported role of interleukin-17A in the stimulation of granulopoiesis and neutrophil trafficking," they noted.

A limitation of both ERASURE and FIXTURE was that few patients continued to receive placebo after week 12, thus limiting the comparisons with the placebo group during the maintenance periods. Also, the study populations may have been too small to detect rare adverse events, the authors wrote, noting that extension studies to evaluate long-term efficacy are ongoing.

ERASURE and FIXTURE were supported by Novartis Pharmaceuticals. Dr. Langley reported no conflicts related to these studies. Dr. Elewski disclosed funding from Novartis during the study period.

At least two-thirds of adults with plaque psoriasis treated with the fully human anti-interleukin-17A monoclonal antibody secukinumab achieved PASI 75 at 12 weeks in two related randomized phase III trials. The findings were reported online July 9 in the New England Journal of Medicine.

In the ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) trial, a multicenter, double-blind study involving 738 patients, the proportions of patients who achieved a 75% or greater reduction in Psoriasis Area and Severity Index (PASI 75) score at 12 weeks were 81.6%, 71.6%, and 4.5% with 300 mg of secukinumab, 150 mg of secukinumab, and placebo, respectively.

In the FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens) study, a multicenter, double-blind, active-controlled study involving 1,306 patients, the proportions meeting PASI 75 were 77.1% and 67% for 300 and 150 mg, respectively, compared with 44% for etanercept and 4.9% for placebo.

The difference between each secukinumab dose and its comparators was statistically significant in both studies, Dr. Richard G. Langley of Dalhousie University, Halifax, N.S., Dr. Boni Elewski of the University of Alabama, Birmingham, and their colleagues reported on behalf of the ERASURE and FIXTURE Study Groups.

The investigators also found that the proportions of patients with a response of 0 or 1 on the modified investigator’s global assessment at 12 weeks were 65.3%, 51.2%, and 2.4% for the 300- and 150-mg secukinumab doses and placebo, respectively, in ERASURE; and 62.5% and 51.1% for the 300- and 150-mg doses, 27.2% for etanercept, and 2.8% for placebo in FIXTURE (N. Engl. J. Med. 2014 July 9 [doi: 10.1056/NE/NEJMoa314258]).

The differences between each secukinumab dose and its comparators were significant for this measure as well, the investigators reported.

Secukinumab at the 300- and 150-mg doses in both ERASURE and FIXTURE was also superior to placebo (and in FIXTURE, superior to etanercept) for all secondary efficacy endpoints, including PASI 90 and PASI 100 response at week 12; patient reports of itching, pain, and scaling on the Psoriasis Symptom Diary at week 12; and Dermatology Life Quality Index scores.

Both ERASURE and FIXTURE were designed to evaluate the safety of secukinumab as induction therapy with assessment at week 12, and as maintenance therapy with assessment at week 52. Subjects were aged 18 years or older with poorly controlled, moderate to severe plaque psoriasis that had been diagnosed at least 6 months prior, and with a PASI score of 12 or higher, a modified investigator’s global assessment score of 3 or 4, and involvement of 10% or more of their body surface area.

ERASURE was conducted from June 2011 to April 2013 at 88 sites worldwide, and FIXTURE was conducted from June 2011 to June 2013 at 231 sites. Patients in the 300-mg groups received two 150-mg subcutaneous injections of secukinumab, and those in the 150-mg group received one 150-mg injection of secukinumab, and one placebo injection. Etanercept was given at a dose of 50 mg administered subcutaneously twice weekly from baseline until week 12, and then once weekly through week 51.

Adverse events were more common in patients treated with secukinumab in ERASURE; 55% of patients in the 300-mg group, 60.4% in the 150-mg group, and 47% in the placebo group experienced at least one adverse event during the induction period, and 29.4%, 26.9%, and 16.2% in those groups, respectively, experienced infections and/or infestations. The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection.

The incidence of adverse events in FIXTURE was similar in those receiving secukinumab and etanercept, and was greater in both groups than in the placebo group. Infections and infestations occurred in 26.7%, 30.9%, 24.5%, and 19.3% of those receiving 300 mg of secukinumab, 150 mg of secukinumab, etanercept, and placebo, respectively. However, candida infections were more common with secukinumab than with etanercept (4.7%, 2.3%, and 1.2% of patients in the 300- and 150-mg secukinumab groups and the etanercept group, respectively, had candida infections). All candida infections in the secukinumab group were mild or moderate, and two of four infections in the etanercept group were severe.

Grade 3 neutropenia occurred in nine patients receiving secukinumab and in no patients receiving etanercept.

"The results of these phase 3 studies validate interleukin-17A as an important therapeutic target in moderate to severe plaque psoriasis, confirming earlier findings from basic research and phase 2 trials of secukinumab that suggested that interleukin-17A plays a role in the pathogenesis of psoriasis," the investigators said.

Interleukin-17A plays a key role in host defense, specifically in mucocutaneous microbial surveillance, they added.

"Continued vigilance with respect to the potential for candida infection will be necessary for interleukin-17A inhibitors. Neutropenia may also be of potential concern because of the reported role of interleukin-17A in the stimulation of granulopoiesis and neutrophil trafficking," they noted.

A limitation of both ERASURE and FIXTURE was that few patients continued to receive placebo after week 12, thus limiting the comparisons with the placebo group during the maintenance periods. Also, the study populations may have been too small to detect rare adverse events, the authors wrote, noting that extension studies to evaluate long-term efficacy are ongoing.

ERASURE and FIXTURE were supported by Novartis Pharmaceuticals. Dr. Langley reported no conflicts related to these studies. Dr. Elewski disclosed funding from Novartis during the study period.

A 25-year-old man with plaque psoriasis and virtually no hair of any sort now sports a full head of hair plus body hair after treatment with the arthritis drug tofacitinib, according to Dr. Brittany G. Craiglow and Dr. Brett A. King of Yale University, New Haven, Conn.

The treatment has been so successful that Dr. King has submitted a proposal for a clinical trial involving a cream form of tofacitinib as a treatment for alopecia areata, according to a statement from the university.

Tofacitinib is approved only for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate, but it is in clinical development for the treatment of psoriasis.

Dr. Craiglow and Dr. King began treating the patient with 10 mg oral tofacitinib (Xeljanz) daily. At baseline, the patient had been diagnosed with plaque psoriasis and alopecia universalis. His only body hair was a small amount of hair within the psoriasis plaques on his head, the researchers said (J. Invest. Dermatol. 2014 June 18 [doi:10.1038/jid.2014.260]). 

After 2 months of tofacitinib dosed at 5 mg twice daily, the psoriasis on the patient’s scalp, torso, and elbows showed some improvement, and there was some hair growth on his face and scalp. The researchers increased the dose to 10 mg in the morning and 5 mg at night. After 3 more months, the patient had complete regrowth of scalp hair, as well as some growth of eyebrows, eyelashes, armpit hair, and pubic hair. After 8 months, the patient had full regrowth of all body hair, with the exception of hair on the arms and legs (which had been sparse prior to his alopecia diagnosis, the researchers said).

Although the hair growth has been dramatic, improvements in the patient’s psoriasis have been slower, likely because of the dosage.

“While we considered increasing the dose of tofacitinib, the patient is so pleased with the regrowth of his hair (and is not particularly bothered by the remaining psoriasis) that he has chosen to continue at the present dose,” the researchers noted.

The researchers considered using tofacitinib to treat the patient’s alopecia universalis based on the research of Angela M. Christiano, Ph.D., of Columbia University, New York, in which the drug reversed hair loss in a mouse model of alopecia areata.

The patient has reported no side effects, and lab testing has shown no abnormalities in complete blood count, serum creatinine, electrolytes, liver function, glucose, or lipids, the researchers noted.
The researchers had no financial conflicts to disclose.

hsplete@frontlinemedcom.com

A 25-year-old man with plaque psoriasis and virtually no hair of any sort now sports a full head of hair plus body hair after treatment with the arthritis drug tofacitinib, according to Dr. Brittany G. Craiglow and Dr. Brett A. King of Yale University, New Haven, Conn.

The treatment has been so successful that Dr. King has submitted a proposal for a clinical trial involving a cream form of tofacitinib as a treatment for alopecia areata, according to a statement from the university.

Tofacitinib is approved only for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate, but it is in clinical development for the treatment of psoriasis.

Dr. Craiglow and Dr. King began treating the patient with 10 mg oral tofacitinib (Xeljanz) daily. At baseline, the patient had been diagnosed with plaque psoriasis and alopecia universalis. His only body hair was a small amount of hair within the psoriasis plaques on his head, the researchers said (J. Invest. Dermatol. 2014 June 18 [doi:10.1038/jid.2014.260]). 

After 2 months of tofacitinib dosed at 5 mg twice daily, the psoriasis on the patient’s scalp, torso, and elbows showed some improvement, and there was some hair growth on his face and scalp. The researchers increased the dose to 10 mg in the morning and 5 mg at night. After 3 more months, the patient had complete regrowth of scalp hair, as well as some growth of eyebrows, eyelashes, armpit hair, and pubic hair. After 8 months, the patient had full regrowth of all body hair, with the exception of hair on the arms and legs (which had been sparse prior to his alopecia diagnosis, the researchers said).

Although the hair growth has been dramatic, improvements in the patient’s psoriasis have been slower, likely because of the dosage.

“While we considered increasing the dose of tofacitinib, the patient is so pleased with the regrowth of his hair (and is not particularly bothered by the remaining psoriasis) that he has chosen to continue at the present dose,” the researchers noted.

The researchers considered using tofacitinib to treat the patient’s alopecia universalis based on the research of Angela M. Christiano, Ph.D., of Columbia University, New York, in which the drug reversed hair loss in a mouse model of alopecia areata.

The patient has reported no side effects, and lab testing has shown no abnormalities in complete blood count, serum creatinine, electrolytes, liver function, glucose, or lipids, the researchers noted.
The researchers had no financial conflicts to disclose.

hsplete@frontlinemedcom.com

A 25-year-old man with plaque psoriasis and virtually no hair of any sort now sports a full head of hair plus body hair after treatment with the arthritis drug tofacitinib, according to Dr. Brittany G. Craiglow and Dr. Brett A. King of Yale University, New Haven, Conn.

The treatment has been so successful that Dr. King has submitted a proposal for a clinical trial involving a cream form of tofacitinib as a treatment for alopecia areata, according to a statement from the university.

Tofacitinib is approved only for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate, but it is in clinical development for the treatment of psoriasis.

Dr. Craiglow and Dr. King began treating the patient with 10 mg oral tofacitinib (Xeljanz) daily. At baseline, the patient had been diagnosed with plaque psoriasis and alopecia universalis. His only body hair was a small amount of hair within the psoriasis plaques on his head, the researchers said (J. Invest. Dermatol. 2014 June 18 [doi:10.1038/jid.2014.260]). 

After 2 months of tofacitinib dosed at 5 mg twice daily, the psoriasis on the patient’s scalp, torso, and elbows showed some improvement, and there was some hair growth on his face and scalp. The researchers increased the dose to 10 mg in the morning and 5 mg at night. After 3 more months, the patient had complete regrowth of scalp hair, as well as some growth of eyebrows, eyelashes, armpit hair, and pubic hair. After 8 months, the patient had full regrowth of all body hair, with the exception of hair on the arms and legs (which had been sparse prior to his alopecia diagnosis, the researchers said).

Although the hair growth has been dramatic, improvements in the patient’s psoriasis have been slower, likely because of the dosage.

“While we considered increasing the dose of tofacitinib, the patient is so pleased with the regrowth of his hair (and is not particularly bothered by the remaining psoriasis) that he has chosen to continue at the present dose,” the researchers noted.

The researchers considered using tofacitinib to treat the patient’s alopecia universalis based on the research of Angela M. Christiano, Ph.D., of Columbia University, New York, in which the drug reversed hair loss in a mouse model of alopecia areata.

The patient has reported no side effects, and lab testing has shown no abnormalities in complete blood count, serum creatinine, electrolytes, liver function, glucose, or lipids, the researchers noted.
The researchers had no financial conflicts to disclose.

hsplete@frontlinemedcom.com