New treatments for psoriatic arthritis are changing management

DESTIN, FLA. – Revolutionary advances in the treatment of psoriatic arthritis in recent years – particularly the advent of highly effective biologic therapies like tumor necrosis factor inhibitors – are opening other doors in the management of the disease, as well, according to Dr. Arthur Kavanaugh.

"One of the tangible benefits that came from the increased research in psoriatic arthritis is that it got all of us thinking not just about new therapies, but also about the disease itself," Dr. Kavanaugh, professor of medicine at the University of California, San Diego, said at the annual Congress of Clinical Rheumatology.

The "tremendous uptick" in interest in psoriatic arthritis – as evidenced by a surge in the annual number of related articles available at PubMed over the past decade or so – has helped drive collaborative efforts to further improve the care of patients with this complex condition. Rheumatologists and dermatologists came together, for example, to form the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), which has developed treatment recommendations in light of the new therapies, he said.

"All the different domains of disease, which all of us really assess and take into account as we see patients in our clinic – we needed to consider these in ways separate [from the disease as a whole], and see what the data were for them," he said, adding that psoriatic arthritis doesn’t lend itself to a very strict algorithm.

"Psoriatic arthritis is still an art; you still have to talk to the patient. Some patients have horrible peripheral arthritis and have never had dactylitis; some people have really bad dactylitis, and that’s really their main complaint. It’s been really exciting to learn more about how to capture all of these elements," he said.

The success with new treatments has opened up more conversation about how to approach the disease. Dr. Kavanaugh reviewed a few of the changes in the approach to psoriatic arthritis that highlight recent advances.

"We’ve come pretty far, and now we’re talking about how to manage people in a more comprehensive way," he said, explaining that:

• More attention is being paid to other areas of disease involvement.

Management is no longer just about skin disease. Attention is being paid both in trials and in the clinic to other disease characteristics, such as nail involvement.

"It’s not life threatening, but it is life changing," he said, noting that nail involvement in psoriatic arthritis can be painful, may be associated with distal interphalangeal joint arthritis, and can cause patients to feel self-conscious.

"So this is an important area of involvement, and we’re starting to say that in clinical trials we really ought to capture this, we really ought to look at what effect a new drug has on the skin and nails," said.

Similarly, dactylitis, enthesitis, and structural damage are garnering more attention, he said.

"We’re using adjunctive measures better. We’re using disease-modifying antirheumatic drugs more. We’re seeing patients early. We’re treating patients a little earlier," he said.

• More information is emerging about factors that affect treatment response.

Currently there are five tumor necrosis factor (TNF) inhibitors available, all of which are approved for psoriatic arthritis. What has been unclear is whether switching TNF inhibitors is an effective treatment strategy.

"It looks as if it can work," he said referring to findings from the RAPID-PsA study, which showed that certolizumab pegol (Cimzia) was effective in psoriatic arthritis – including in patients with prior TNF inhibitor therapy (Ann. Rheum. Dis. 2014;73:48-55).

Information from the Scandinavian NOR-DMARD (Ann. Rheum. Dis. 2013;72:1840-4) and DANBIO (Arthritis Rheum. 2013;65:1213-23) registries also provide some guidance on switching TNF inhibitors. The data from the two registries were not so different, but the interpretation was different, Dr. Kavanaugh said, explaining that the former’s findings were interpreted to mean that another mechanism should be tried if an initial TNF inhibitor fails; the latter was interpreted to suggest that trying a second TNF inhibitor is reasonable.

"I think both are correct. ... A second TNF inhibitor certainly can work. Maybe it doesn’t work as well as the first, maybe the third doesn’t work as well as the second, but switching certainly does seem to be a viable idea," he said, adding that nonetheless, "additional mechanisms of action certainly give us something to look forward to."

Another issue is the effect of obesity on treatment outcomes. Multiple studies show that losing weight has beneficial effects not only on psoriatic arthritis, but on response to TNF inhibitors.

"Obesity is an incredibly important factor. ... Study after study shows that," he said, noting that in the CORRONA (Consortium of Rheumatology Researchers of North America Inc.) study of patients starting a TNF inhibitor, the only factor that predicted treatment duration and response was obesity.

This has been shown to be true for both weight-based and fix-dosed treatment.

"So it’s not just that fat people aren’t getting enough of the drug, compared to the skinny people. It’s that obesity – as we’ve learned from our dermatology colleagues – is inflammatory and it’s something to be reckoned with," he said.

Weight loss really needs to be stressed to overweight patients in the clinic, he said.

• Important questions are being asked.

"Unlike for rheumatoid arthritis, we still don’t know if methotrexate and TNF inhibitors are synergistic. ... That’s a gap I would love to see filled in our psoriatic arthritis understanding," he said.

Another important idea that is being addressed involves thinking of how different means of attacking the immune system have disparate results in various immune diseases, thus showing that the diseases may be similar but are not the same.

Dr. Kavanaugh called this a "bedside-to-bench" phenomenon, in which treatment outcomes provide improved understanding of the disease processes.

Targeting interleukin (IL)-6, for example, works very well in RA, juvenile idiopathic arthritis (JIA), and systemic JIA, but it doesn’t work so well in ankylosing spondylitis, and it doesn’t appear that it will work well in several other conditions, based on anecdotal reports.

Similarly, drugs that target IL-17 – a very exciting prospect in psoriasis – don’t seem to work so well in RA. IL-17 inhibition theoretically should work well in inflammatory bowel disease, but it actually appears to make Crohn’s disease worse, he noted.

"We now have newer therapeutic approaches, and it’s very exciting, because we’re going to think of these diseases a little bit differently and almost define the diseases by how they respond to different focal immunomodulatory interventions," he said.

• New treatment targets and approaches are emerging.

There has been some question as to whether IL-23, which is known to be an important driver of IL-17, will be the mechanism by which IL-17 works.

Three IL-17 inhibitors are currently in development. Results in skin psoriasis have been remarkable, and there is a great deal of excitement about them, but data are just beginning to emerge for psoriatic arthritis, Dr. Kavanaugh said.

In an extension study reported at the 2013 annual meeting of the American College of Rheumatology (ACR), for example, the anti-IL-17 receptor A monoclonal antibody brodalumab demonstrated possible increased efficacy through 24 weeks of treatment.

"It’s very exciting to see new data. These drugs will come almost certainly to the clinic first for psoriasis, but I think if they are shown to have good effects in psoriatic arthritis, they will be available to us as another option in our patients," he said.

As for new treatment strategies, psoriatic arthritis is catching up with rheumatoid arthritis with respect to attention to tight control.

"The idea is to evaluate patients, and if they are not reaching a goal, you change treatment. That is the basis for TICOPA – tight control of early psoriatic arthritis," he said.

Joint and skin outcomes were significantly improved in patients in the 48-week, open-label, randomized controlled trial who were treated using a treat-to-target approach, compared with those treated with usual care, according to findings presented at ACR 2013.

However, more serious adverse events occurred in the tight control group (14 vs. 6 in the usual care group), Dr. Kavanaugh noted.

"So I think it’s a thought exercise. I think it shows us that tight control works in psoriatic arthritis. If you follow people very regularly, if you demand that they achieve a good goal like minimal disease activity, they are going to do better," he said.

The downside of increased adverse events raises interesting issues of value and pharmacoeconomics, he noted.

Another "superhot issue in psoriatic arthritis" is whether therapy – and particularly biologic therapy – can be stopped or tapered in patients who are doing very well. A number of studies are looking at this, and it’s an important issue that payers are interested in considering, but data are currently limited.

Based on data that are available, it appears that discontinuing therapy abruptly is not a good idea. In one small study, 77% of patients who discontinued therapy had a disease flare, with greater risk among those with longer treatment duration. Restart of treatment was effective in all cases.

"Certainly there is going to be a lot more interest in this in rheumatoid arthritis, and I think it’s going to spill over and we’ll see more studies in this in psoriatic arthritis as well," he said.

Dr. Kavanaugh reported having no financial disclosures.

DESTIN, FLA. – Revolutionary advances in the treatment of psoriatic arthritis in recent years – particularly the advent of highly effective biologic therapies like tumor necrosis factor inhibitors – are opening other doors in the management of the disease, as well, according to Dr. Arthur Kavanaugh.

"One of the tangible benefits that came from the increased research in psoriatic arthritis is that it got all of us thinking not just about new therapies, but also about the disease itself," Dr. Kavanaugh, professor of medicine at the University of California, San Diego, said at the annual Congress of Clinical Rheumatology.

The "tremendous uptick" in interest in psoriatic arthritis – as evidenced by a surge in the annual number of related articles available at PubMed over the past decade or so – has helped drive collaborative efforts to further improve the care of patients with this complex condition. Rheumatologists and dermatologists came together, for example, to form the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), which has developed treatment recommendations in light of the new therapies, he said.

"All the different domains of disease, which all of us really assess and take into account as we see patients in our clinic – we needed to consider these in ways separate [from the disease as a whole], and see what the data were for them," he said, adding that psoriatic arthritis doesn’t lend itself to a very strict algorithm.

"Psoriatic arthritis is still an art; you still have to talk to the patient. Some patients have horrible peripheral arthritis and have never had dactylitis; some people have really bad dactylitis, and that’s really their main complaint. It’s been really exciting to learn more about how to capture all of these elements," he said.

The success with new treatments has opened up more conversation about how to approach the disease. Dr. Kavanaugh reviewed a few of the changes in the approach to psoriatic arthritis that highlight recent advances.

"We’ve come pretty far, and now we’re talking about how to manage people in a more comprehensive way," he said, explaining that:

• More attention is being paid to other areas of disease involvement.

Management is no longer just about skin disease. Attention is being paid both in trials and in the clinic to other disease characteristics, such as nail involvement.

"It’s not life threatening, but it is life changing," he said, noting that nail involvement in psoriatic arthritis can be painful, may be associated with distal interphalangeal joint arthritis, and can cause patients to feel self-conscious.

"So this is an important area of involvement, and we’re starting to say that in clinical trials we really ought to capture this, we really ought to look at what effect a new drug has on the skin and nails," said.

Similarly, dactylitis, enthesitis, and structural damage are garnering more attention, he said.

"We’re using adjunctive measures better. We’re using disease-modifying antirheumatic drugs more. We’re seeing patients early. We’re treating patients a little earlier," he said.

• More information is emerging about factors that affect treatment response.

Currently there are five tumor necrosis factor (TNF) inhibitors available, all of which are approved for psoriatic arthritis. What has been unclear is whether switching TNF inhibitors is an effective treatment strategy.

"It looks as if it can work," he said referring to findings from the RAPID-PsA study, which showed that certolizumab pegol (Cimzia) was effective in psoriatic arthritis – including in patients with prior TNF inhibitor therapy (Ann. Rheum. Dis. 2014;73:48-55).

Information from the Scandinavian NOR-DMARD (Ann. Rheum. Dis. 2013;72:1840-4) and DANBIO (Arthritis Rheum. 2013;65:1213-23) registries also provide some guidance on switching TNF inhibitors. The data from the two registries were not so different, but the interpretation was different, Dr. Kavanaugh said, explaining that the former’s findings were interpreted to mean that another mechanism should be tried if an initial TNF inhibitor fails; the latter was interpreted to suggest that trying a second TNF inhibitor is reasonable.

"I think both are correct. ... A second TNF inhibitor certainly can work. Maybe it doesn’t work as well as the first, maybe the third doesn’t work as well as the second, but switching certainly does seem to be a viable idea," he said, adding that nonetheless, "additional mechanisms of action certainly give us something to look forward to."

Another issue is the effect of obesity on treatment outcomes. Multiple studies show that losing weight has beneficial effects not only on psoriatic arthritis, but on response to TNF inhibitors.

"Obesity is an incredibly important factor. ... Study after study shows that," he said, noting that in the CORRONA (Consortium of Rheumatology Researchers of North America Inc.) study of patients starting a TNF inhibitor, the only factor that predicted treatment duration and response was obesity.

This has been shown to be true for both weight-based and fix-dosed treatment.

"So it’s not just that fat people aren’t getting enough of the drug, compared to the skinny people. It’s that obesity – as we’ve learned from our dermatology colleagues – is inflammatory and it’s something to be reckoned with," he said.

Weight loss really needs to be stressed to overweight patients in the clinic, he said.

• Important questions are being asked.

"Unlike for rheumatoid arthritis, we still don’t know if methotrexate and TNF inhibitors are synergistic. ... That’s a gap I would love to see filled in our psoriatic arthritis understanding," he said.

Another important idea that is being addressed involves thinking of how different means of attacking the immune system have disparate results in various immune diseases, thus showing that the diseases may be similar but are not the same.

Dr. Kavanaugh called this a "bedside-to-bench" phenomenon, in which treatment outcomes provide improved understanding of the disease processes.

Targeting interleukin (IL)-6, for example, works very well in RA, juvenile idiopathic arthritis (JIA), and systemic JIA, but it doesn’t work so well in ankylosing spondylitis, and it doesn’t appear that it will work well in several other conditions, based on anecdotal reports.

Similarly, drugs that target IL-17 – a very exciting prospect in psoriasis – don’t seem to work so well in RA. IL-17 inhibition theoretically should work well in inflammatory bowel disease, but it actually appears to make Crohn’s disease worse, he noted.

"We now have newer therapeutic approaches, and it’s very exciting, because we’re going to think of these diseases a little bit differently and almost define the diseases by how they respond to different focal immunomodulatory interventions," he said.

• New treatment targets and approaches are emerging.

There has been some question as to whether IL-23, which is known to be an important driver of IL-17, will be the mechanism by which IL-17 works.

Three IL-17 inhibitors are currently in development. Results in skin psoriasis have been remarkable, and there is a great deal of excitement about them, but data are just beginning to emerge for psoriatic arthritis, Dr. Kavanaugh said.

In an extension study reported at the 2013 annual meeting of the American College of Rheumatology (ACR), for example, the anti-IL-17 receptor A monoclonal antibody brodalumab demonstrated possible increased efficacy through 24 weeks of treatment.

"It’s very exciting to see new data. These drugs will come almost certainly to the clinic first for psoriasis, but I think if they are shown to have good effects in psoriatic arthritis, they will be available to us as another option in our patients," he said.

As for new treatment strategies, psoriatic arthritis is catching up with rheumatoid arthritis with respect to attention to tight control.

"The idea is to evaluate patients, and if they are not reaching a goal, you change treatment. That is the basis for TICOPA – tight control of early psoriatic arthritis," he said.

Joint and skin outcomes were significantly improved in patients in the 48-week, open-label, randomized controlled trial who were treated using a treat-to-target approach, compared with those treated with usual care, according to findings presented at ACR 2013.

However, more serious adverse events occurred in the tight control group (14 vs. 6 in the usual care group), Dr. Kavanaugh noted.

"So I think it’s a thought exercise. I think it shows us that tight control works in psoriatic arthritis. If you follow people very regularly, if you demand that they achieve a good goal like minimal disease activity, they are going to do better," he said.

The downside of increased adverse events raises interesting issues of value and pharmacoeconomics, he noted.

Another "superhot issue in psoriatic arthritis" is whether therapy – and particularly biologic therapy – can be stopped or tapered in patients who are doing very well. A number of studies are looking at this, and it’s an important issue that payers are interested in considering, but data are currently limited.

Based on data that are available, it appears that discontinuing therapy abruptly is not a good idea. In one small study, 77% of patients who discontinued therapy had a disease flare, with greater risk among those with longer treatment duration. Restart of treatment was effective in all cases.

"Certainly there is going to be a lot more interest in this in rheumatoid arthritis, and I think it’s going to spill over and we’ll see more studies in this in psoriatic arthritis as well," he said.

Dr. Kavanaugh reported having no financial disclosures.

DESTIN, FLA. – Revolutionary advances in the treatment of psoriatic arthritis in recent years – particularly the advent of highly effective biologic therapies like tumor necrosis factor inhibitors – are opening other doors in the management of the disease, as well, according to Dr. Arthur Kavanaugh.

"One of the tangible benefits that came from the increased research in psoriatic arthritis is that it got all of us thinking not just about new therapies, but also about the disease itself," Dr. Kavanaugh, professor of medicine at the University of California, San Diego, said at the annual Congress of Clinical Rheumatology.

The "tremendous uptick" in interest in psoriatic arthritis – as evidenced by a surge in the annual number of related articles available at PubMed over the past decade or so – has helped drive collaborative efforts to further improve the care of patients with this complex condition. Rheumatologists and dermatologists came together, for example, to form the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), which has developed treatment recommendations in light of the new therapies, he said.

"All the different domains of disease, which all of us really assess and take into account as we see patients in our clinic – we needed to consider these in ways separate [from the disease as a whole], and see what the data were for them," he said, adding that psoriatic arthritis doesn’t lend itself to a very strict algorithm.

"Psoriatic arthritis is still an art; you still have to talk to the patient. Some patients have horrible peripheral arthritis and have never had dactylitis; some people have really bad dactylitis, and that’s really their main complaint. It’s been really exciting to learn more about how to capture all of these elements," he said.

The success with new treatments has opened up more conversation about how to approach the disease. Dr. Kavanaugh reviewed a few of the changes in the approach to psoriatic arthritis that highlight recent advances.

"We’ve come pretty far, and now we’re talking about how to manage people in a more comprehensive way," he said, explaining that:

• More attention is being paid to other areas of disease involvement.

Management is no longer just about skin disease. Attention is being paid both in trials and in the clinic to other disease characteristics, such as nail involvement.

"It’s not life threatening, but it is life changing," he said, noting that nail involvement in psoriatic arthritis can be painful, may be associated with distal interphalangeal joint arthritis, and can cause patients to feel self-conscious.

"So this is an important area of involvement, and we’re starting to say that in clinical trials we really ought to capture this, we really ought to look at what effect a new drug has on the skin and nails," said.

Similarly, dactylitis, enthesitis, and structural damage are garnering more attention, he said.

"We’re using adjunctive measures better. We’re using disease-modifying antirheumatic drugs more. We’re seeing patients early. We’re treating patients a little earlier," he said.

• More information is emerging about factors that affect treatment response.

Currently there are five tumor necrosis factor (TNF) inhibitors available, all of which are approved for psoriatic arthritis. What has been unclear is whether switching TNF inhibitors is an effective treatment strategy.

"It looks as if it can work," he said referring to findings from the RAPID-PsA study, which showed that certolizumab pegol (Cimzia) was effective in psoriatic arthritis – including in patients with prior TNF inhibitor therapy (Ann. Rheum. Dis. 2014;73:48-55).

Information from the Scandinavian NOR-DMARD (Ann. Rheum. Dis. 2013;72:1840-4) and DANBIO (Arthritis Rheum. 2013;65:1213-23) registries also provide some guidance on switching TNF inhibitors. The data from the two registries were not so different, but the interpretation was different, Dr. Kavanaugh said, explaining that the former’s findings were interpreted to mean that another mechanism should be tried if an initial TNF inhibitor fails; the latter was interpreted to suggest that trying a second TNF inhibitor is reasonable.

"I think both are correct. ... A second TNF inhibitor certainly can work. Maybe it doesn’t work as well as the first, maybe the third doesn’t work as well as the second, but switching certainly does seem to be a viable idea," he said, adding that nonetheless, "additional mechanisms of action certainly give us something to look forward to."

Another issue is the effect of obesity on treatment outcomes. Multiple studies show that losing weight has beneficial effects not only on psoriatic arthritis, but on response to TNF inhibitors.

"Obesity is an incredibly important factor. ... Study after study shows that," he said, noting that in the CORRONA (Consortium of Rheumatology Researchers of North America Inc.) study of patients starting a TNF inhibitor, the only factor that predicted treatment duration and response was obesity.

This has been shown to be true for both weight-based and fix-dosed treatment.

"So it’s not just that fat people aren’t getting enough of the drug, compared to the skinny people. It’s that obesity – as we’ve learned from our dermatology colleagues – is inflammatory and it’s something to be reckoned with," he said.

Weight loss really needs to be stressed to overweight patients in the clinic, he said.

• Important questions are being asked.

"Unlike for rheumatoid arthritis, we still don’t know if methotrexate and TNF inhibitors are synergistic. ... That’s a gap I would love to see filled in our psoriatic arthritis understanding," he said.

Another important idea that is being addressed involves thinking of how different means of attacking the immune system have disparate results in various immune diseases, thus showing that the diseases may be similar but are not the same.

Dr. Kavanaugh called this a "bedside-to-bench" phenomenon, in which treatment outcomes provide improved understanding of the disease processes.

Targeting interleukin (IL)-6, for example, works very well in RA, juvenile idiopathic arthritis (JIA), and systemic JIA, but it doesn’t work so well in ankylosing spondylitis, and it doesn’t appear that it will work well in several other conditions, based on anecdotal reports.

Similarly, drugs that target IL-17 – a very exciting prospect in psoriasis – don’t seem to work so well in RA. IL-17 inhibition theoretically should work well in inflammatory bowel disease, but it actually appears to make Crohn’s disease worse, he noted.

"We now have newer therapeutic approaches, and it’s very exciting, because we’re going to think of these diseases a little bit differently and almost define the diseases by how they respond to different focal immunomodulatory interventions," he said.

• New treatment targets and approaches are emerging.

There has been some question as to whether IL-23, which is known to be an important driver of IL-17, will be the mechanism by which IL-17 works.

Three IL-17 inhibitors are currently in development. Results in skin psoriasis have been remarkable, and there is a great deal of excitement about them, but data are just beginning to emerge for psoriatic arthritis, Dr. Kavanaugh said.

In an extension study reported at the 2013 annual meeting of the American College of Rheumatology (ACR), for example, the anti-IL-17 receptor A monoclonal antibody brodalumab demonstrated possible increased efficacy through 24 weeks of treatment.

"It’s very exciting to see new data. These drugs will come almost certainly to the clinic first for psoriasis, but I think if they are shown to have good effects in psoriatic arthritis, they will be available to us as another option in our patients," he said.

As for new treatment strategies, psoriatic arthritis is catching up with rheumatoid arthritis with respect to attention to tight control.

"The idea is to evaluate patients, and if they are not reaching a goal, you change treatment. That is the basis for TICOPA – tight control of early psoriatic arthritis," he said.

Joint and skin outcomes were significantly improved in patients in the 48-week, open-label, randomized controlled trial who were treated using a treat-to-target approach, compared with those treated with usual care, according to findings presented at ACR 2013.

However, more serious adverse events occurred in the tight control group (14 vs. 6 in the usual care group), Dr. Kavanaugh noted.

"So I think it’s a thought exercise. I think it shows us that tight control works in psoriatic arthritis. If you follow people very regularly, if you demand that they achieve a good goal like minimal disease activity, they are going to do better," he said.

The downside of increased adverse events raises interesting issues of value and pharmacoeconomics, he noted.

Another "superhot issue in psoriatic arthritis" is whether therapy – and particularly biologic therapy – can be stopped or tapered in patients who are doing very well. A number of studies are looking at this, and it’s an important issue that payers are interested in considering, but data are currently limited.

Based on data that are available, it appears that discontinuing therapy abruptly is not a good idea. In one small study, 77% of patients who discontinued therapy had a disease flare, with greater risk among those with longer treatment duration. Restart of treatment was effective in all cases.

"Certainly there is going to be a lot more interest in this in rheumatoid arthritis, and I think it’s going to spill over and we’ll see more studies in this in psoriatic arthritis as well," he said.

Dr. Kavanaugh reported having no financial disclosures.