Early Decisions and Impact: An IL-23 Inhibitor in Bio-Naive Patients With PsA Save
Sponsored by AbbVie Medical Affairs + Health Impact 
Transcription
To RoomNow. This podcast is sponsored by and developed by AbbVie US Medical Affairs. My name is Alvin Wells. I'm a board certified rheumatologist. I'm the director of rheumatology at the American Medical Group in Destin, Florida.
I'm pleased to have one of my colleagues join me today, Doctor. Singla. Welcome to the podcast. Do you mind introducing yourself?
I'm Shika Singla. I'm an associate professor at the Medical College of Wisconsin and the director of the psoriatic arthritis program.
If you have a patient who has psoriatic arthritis, we know they can't get into the clinic to see us tomorrow. And research says if a patient with PSA has a diagnosis or delay of over a year, that's going to result in worse disease progression and reduced remission rates. There's also data shows that even a diagnostic delay of six months has been associated with more radiologic damage and functional limitations. Such studies suggest that an earlier diagnosis and earlier treatment is what we really should be focusing on. Let's talk about that and what that really means for our patient with PSA and some of the long term benefits.
Doctor. Zingma?
Doctor. Wells, an abstract presented earlier this year at EULAR showed that patients with newly diagnosed moderate to severe psoriatic arthritis treated with biologics had better arthritis and skin outcomes, and these were measured by DAPSA and PASI scores at week twenty four compared to patients receiving a standard conventional DMAR therapy. While some data potentially support the idea of treating psoriatic arthritis fast and hard with a biologic, how to best position biologics in PSA treatment algorithm is still being established.
What gets you motivated about treating a patient who is biologic naive and what kind of things you take into mind?
I believe in shared decision making and individualized care for my patients. When evaluating a patient, I pay attention to the predominant disease manifestations and severity of the disease. I also consider comorbidities such as depression, anxiety, diabetes, and inflammatory bowel disease. The lifetime risk for developing IBD is more than four times greater for patients with psoriatic arthritis than in the general population. This risk should be considered when selecting therapies, as some treatments for psoriatic arthritis may worsen or improve IBD.
According to GRAPA guidelines, symptoms prompting IBD evaluation in patients with psoriatic arthritis include chronic diarrhea lasting for more than three months, nocturnal bowel symptoms, rectal bleeding, perianal fistulas or abscesses, chronic abdominal pain, and weight loss. In addition to guidelines, a real world analysis based on claims data involving one hundred and thirty thousand patients with psoriatic arthritis highlighted additional risk factors that should be considered, including a history of gastrointestinal procedures or tests, such as stool tests, previous diagnosis of gastroenteritis, nausea, vomiting, and family history of IBD. Identifying these factors is important for appropriate referral and treatment choices.
We also know that there's some research ongoing to providing some long term evidence of outcomes for our patients. Can you talk to the audience about that and introduce the Keepsake Trial program?
Of course, Doctor. Wells. This program was developed to assess the efficacy and safety of risankizumab, let's call it RIZA, an IL-twenty three inhibiting antibody in adult patients with active psoriatic arthritis. There are actually two KEAP SIC trials, both phase three double blinded randomized controlled trials with the primary endpoint of ACR20 at week twenty four. Keepsake one enrolled only bio naive patients and Keepsake two enrolled both bio naive patients and patients who have already been on a biologic and had inadequate response.
We are going to focus on Keepsake one in which four eighty three participants were randomized to receive subcutaneous one hundred fifty milligram RIZA at weeks zero, four and sixteen. And four eighty one participants were randomized to receive placebo. Keepsake one met the primary endpoint, which was ACR20, and 57 of patients achieved this endpoint as compared to about one third of patients on placebo. Additionally, at week 24, they were about one third, thirty three point four percent treated with RIZA who achieved ACR 50 compared to eleven point three percent in the placebo group. And fifty two point three percent of participants treated with VISA who had three or more percentage of body surface area due to psoriasis at baseline achieved 90% skin clearance or PASI 90 compared to about ten percent in the placebo group.
I think the nice thing that you highlight in the Keepsake trial, it not only works for the joints, but also for the skin. Let's take a look at those patients who were on risankizumab as their first biologic. How do they bear long term, particularly with the joint outcomes?
In Keepsake one, an open label extension period at five years showed that seventy three percent of patients out of four eighty three in the RIZA arm remained in the study. And out of these patients, fifty four percent of patients receiving continuous RIZA achieved ACR20, thirty six point two percent achieved ACR50, and thirty three point seven percent achieved minimal disease activity. Looking at radiographic progression, while changes from baseline in psoriatic arthritis modified total Sharpe score did not differ statistically at week 24 between the RIZA and placebo groups, an exploratory analysis was performed. And that showed that ninety two percent of the patients treated with RIZA and eighty eight percent of patients in the placebo arm had no radiographic progression. After five years, eighty eight percent or two ninety eight of three thirty seven patients receiving RIZA showed no radiographic progression.
Doctor. Wells, it is so important to note that open label extension trials like the one we are describing have a potential for enrichment of long term data in the remaining patient population, since the patients who are unable to tolerate or do not respond to the drug often drop out.
So taken together, the Keepsake open label extension suggests its long term benefits in those patients who are bio naive. I also want to discuss the post hoc analysis of the Keepsake trial data that look at the maintenance of clinical responses after five years of RIZA treatment. For bio naive patients in Keepsake one receiving risankizumab, sixty six point seven percent out of two sixty seven patients who achieved ACR20 at week twenty four maintained the ACR20 response at approximately five years. Fifty five percent out of one hundred and fifty one patients who achieved the ACR50 at week twenty four maintained the ACR 50 response at approximately five years. Improvements in skin were also seen with seventy one point five percent of respondents out of one hundred and forty four patients at week twenty four, maintaining the achievement of PASI 90 approximately five years.
Doctor. Vejz, these data provide such valuable information on long term efficacy with risankizumab in both joints and skin.
At the end of the day, we got to balance the efficacy with the safety. So let's talk about some of the long term safety data in patients treated with risankizumab.
At five years in the open label extension of the KEAPSEIC-one trial, no new safety signals were detected, and the safety profile was similar to what was previously reported in patients with psoriasis. In an integrated safety analysis with up to six years of exposure to risankizumab in psoriatic arthritis, the rate of events per one hundred patient years was less than zero point one for hypersensitivity, one point six for serious infection, less than zero point one for opportunistic excluding tuberculosis and herpes zoster. There were no active TB cases. Zero point three for herpes zoster and six point six for hepatic events. The most common adverse events were similar to what you and I see in our clinics, which were upper respiratory tract infections, headaches, fatigue, injection site reactions, and tinea infection.
Additional information regarding the safety of RIZA in patients with psoriatic arthritis can be found on the RoomNow therapeutic updates page. Shared decision making between a rheumatologist and patients with psoriatic arthritis is essential for identifying the most appropriate treatment approach. The long term safety profile of treatment is a critical factor as part of the decision.
So we talked about some of the long term efficacy and safety in patients' PSA, from the clinical trials. Some people say, that doesn't really reflect my practices. I need some real world data. Are there any real world studies out there with risankizumab?
Great question, Doctor. Wells. A real world study in patients with psoriatic arthritis was conducted to evaluate the persistence of first line advanced therapies. Persistence was defined as no treatment switch or discontinuation. The study found that seventy six point three percent of patients with psoriatic arthritis persisted on visa at twelve months.
It is important to note that this study was based on claims data, which can be incomplete, inaccurate, and have missing data sometimes.
I don't know about my audience, but you got me fired up, Doctor. Singla. Because think about what you shared with us today. You talk about it in the clinic. We often focus on the initial effects of a therapy, but guess what?
This is a chronic disease. Need to make sure that patient's going be doing well long term. I like what you said to start the whole podcast. You want to treat early and treat aggressive and use evidence based medicine to help guide you and other providers to getting a patient with psoriatic arthritis under control. These are excellent points, Doctor.
Singlet. Thank you so much for your time and talking with us today.
Thank you so much, Doctor. Wells.
If you'd like to learn more about the Keepsake trials and long term safety of risankizumab in bile naive patients with PSA, check out the RheumNow Therapeutics update page. If you're interested in learning more about the treatment response of risankizumab in bile naive patients, please see the link to our previous RheumNow Therapeutics update shown below this podcast. And finally, please listen to the risankizumab important safety considerations next. Thank you all for your time, and thank you for listening.
Risankizumab, a humanized monoclonal antibody to IL-twenty three, is indicated for the treatment of active psoriatic arthritis in adults, and moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Risinkizumab is contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab or any of the excipients. Serious hypersensitivity reactions, including anaphylaxis, may occur. If a serious hypersensitivity reaction occurs, discontinue risankizumab and initiate appropriate therapy immediately. Risankizumab may increase the risk of infections.
Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, discontinue risinkizumab until the infection resolves. Evaluate patients for tuberculosis infection prior to initiating treatment with risankizumab. Avoid use of live vaccines in patients treated with risankizumab. The most common adverse reactions greater than or equal to one percent are upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.
Review accompanying risankizumab full prescribing information for additional information by visiting www.rxabbi.com/pdf/skyrizipi.pdf or contact AbbVie Medical Information at 30110.
I'm pleased to have one of my colleagues join me today, Doctor. Singla. Welcome to the podcast. Do you mind introducing yourself?
I'm Shika Singla. I'm an associate professor at the Medical College of Wisconsin and the director of the psoriatic arthritis program.
If you have a patient who has psoriatic arthritis, we know they can't get into the clinic to see us tomorrow. And research says if a patient with PSA has a diagnosis or delay of over a year, that's going to result in worse disease progression and reduced remission rates. There's also data shows that even a diagnostic delay of six months has been associated with more radiologic damage and functional limitations. Such studies suggest that an earlier diagnosis and earlier treatment is what we really should be focusing on. Let's talk about that and what that really means for our patient with PSA and some of the long term benefits.
Doctor. Zingma?
Doctor. Wells, an abstract presented earlier this year at EULAR showed that patients with newly diagnosed moderate to severe psoriatic arthritis treated with biologics had better arthritis and skin outcomes, and these were measured by DAPSA and PASI scores at week twenty four compared to patients receiving a standard conventional DMAR therapy. While some data potentially support the idea of treating psoriatic arthritis fast and hard with a biologic, how to best position biologics in PSA treatment algorithm is still being established.
What gets you motivated about treating a patient who is biologic naive and what kind of things you take into mind?
I believe in shared decision making and individualized care for my patients. When evaluating a patient, I pay attention to the predominant disease manifestations and severity of the disease. I also consider comorbidities such as depression, anxiety, diabetes, and inflammatory bowel disease. The lifetime risk for developing IBD is more than four times greater for patients with psoriatic arthritis than in the general population. This risk should be considered when selecting therapies, as some treatments for psoriatic arthritis may worsen or improve IBD.
According to GRAPA guidelines, symptoms prompting IBD evaluation in patients with psoriatic arthritis include chronic diarrhea lasting for more than three months, nocturnal bowel symptoms, rectal bleeding, perianal fistulas or abscesses, chronic abdominal pain, and weight loss. In addition to guidelines, a real world analysis based on claims data involving one hundred and thirty thousand patients with psoriatic arthritis highlighted additional risk factors that should be considered, including a history of gastrointestinal procedures or tests, such as stool tests, previous diagnosis of gastroenteritis, nausea, vomiting, and family history of IBD. Identifying these factors is important for appropriate referral and treatment choices.
We also know that there's some research ongoing to providing some long term evidence of outcomes for our patients. Can you talk to the audience about that and introduce the Keepsake Trial program?
Of course, Doctor. Wells. This program was developed to assess the efficacy and safety of risankizumab, let's call it RIZA, an IL-twenty three inhibiting antibody in adult patients with active psoriatic arthritis. There are actually two KEAP SIC trials, both phase three double blinded randomized controlled trials with the primary endpoint of ACR20 at week twenty four. Keepsake one enrolled only bio naive patients and Keepsake two enrolled both bio naive patients and patients who have already been on a biologic and had inadequate response.
We are going to focus on Keepsake one in which four eighty three participants were randomized to receive subcutaneous one hundred fifty milligram RIZA at weeks zero, four and sixteen. And four eighty one participants were randomized to receive placebo. Keepsake one met the primary endpoint, which was ACR20, and 57 of patients achieved this endpoint as compared to about one third of patients on placebo. Additionally, at week 24, they were about one third, thirty three point four percent treated with RIZA who achieved ACR 50 compared to eleven point three percent in the placebo group. And fifty two point three percent of participants treated with VISA who had three or more percentage of body surface area due to psoriasis at baseline achieved 90% skin clearance or PASI 90 compared to about ten percent in the placebo group.
I think the nice thing that you highlight in the Keepsake trial, it not only works for the joints, but also for the skin. Let's take a look at those patients who were on risankizumab as their first biologic. How do they bear long term, particularly with the joint outcomes?
In Keepsake one, an open label extension period at five years showed that seventy three percent of patients out of four eighty three in the RIZA arm remained in the study. And out of these patients, fifty four percent of patients receiving continuous RIZA achieved ACR20, thirty six point two percent achieved ACR50, and thirty three point seven percent achieved minimal disease activity. Looking at radiographic progression, while changes from baseline in psoriatic arthritis modified total Sharpe score did not differ statistically at week 24 between the RIZA and placebo groups, an exploratory analysis was performed. And that showed that ninety two percent of the patients treated with RIZA and eighty eight percent of patients in the placebo arm had no radiographic progression. After five years, eighty eight percent or two ninety eight of three thirty seven patients receiving RIZA showed no radiographic progression.
Doctor. Wells, it is so important to note that open label extension trials like the one we are describing have a potential for enrichment of long term data in the remaining patient population, since the patients who are unable to tolerate or do not respond to the drug often drop out.
So taken together, the Keepsake open label extension suggests its long term benefits in those patients who are bio naive. I also want to discuss the post hoc analysis of the Keepsake trial data that look at the maintenance of clinical responses after five years of RIZA treatment. For bio naive patients in Keepsake one receiving risankizumab, sixty six point seven percent out of two sixty seven patients who achieved ACR20 at week twenty four maintained the ACR20 response at approximately five years. Fifty five percent out of one hundred and fifty one patients who achieved the ACR50 at week twenty four maintained the ACR 50 response at approximately five years. Improvements in skin were also seen with seventy one point five percent of respondents out of one hundred and forty four patients at week twenty four, maintaining the achievement of PASI 90 approximately five years.
Doctor. Vejz, these data provide such valuable information on long term efficacy with risankizumab in both joints and skin.
At the end of the day, we got to balance the efficacy with the safety. So let's talk about some of the long term safety data in patients treated with risankizumab.
At five years in the open label extension of the KEAPSEIC-one trial, no new safety signals were detected, and the safety profile was similar to what was previously reported in patients with psoriasis. In an integrated safety analysis with up to six years of exposure to risankizumab in psoriatic arthritis, the rate of events per one hundred patient years was less than zero point one for hypersensitivity, one point six for serious infection, less than zero point one for opportunistic excluding tuberculosis and herpes zoster. There were no active TB cases. Zero point three for herpes zoster and six point six for hepatic events. The most common adverse events were similar to what you and I see in our clinics, which were upper respiratory tract infections, headaches, fatigue, injection site reactions, and tinea infection.
Additional information regarding the safety of RIZA in patients with psoriatic arthritis can be found on the RoomNow therapeutic updates page. Shared decision making between a rheumatologist and patients with psoriatic arthritis is essential for identifying the most appropriate treatment approach. The long term safety profile of treatment is a critical factor as part of the decision.
So we talked about some of the long term efficacy and safety in patients' PSA, from the clinical trials. Some people say, that doesn't really reflect my practices. I need some real world data. Are there any real world studies out there with risankizumab?
Great question, Doctor. Wells. A real world study in patients with psoriatic arthritis was conducted to evaluate the persistence of first line advanced therapies. Persistence was defined as no treatment switch or discontinuation. The study found that seventy six point three percent of patients with psoriatic arthritis persisted on visa at twelve months.
It is important to note that this study was based on claims data, which can be incomplete, inaccurate, and have missing data sometimes.
I don't know about my audience, but you got me fired up, Doctor. Singla. Because think about what you shared with us today. You talk about it in the clinic. We often focus on the initial effects of a therapy, but guess what?
This is a chronic disease. Need to make sure that patient's going be doing well long term. I like what you said to start the whole podcast. You want to treat early and treat aggressive and use evidence based medicine to help guide you and other providers to getting a patient with psoriatic arthritis under control. These are excellent points, Doctor.
Singlet. Thank you so much for your time and talking with us today.
Thank you so much, Doctor. Wells.
If you'd like to learn more about the Keepsake trials and long term safety of risankizumab in bile naive patients with PSA, check out the RheumNow Therapeutics update page. If you're interested in learning more about the treatment response of risankizumab in bile naive patients, please see the link to our previous RheumNow Therapeutics update shown below this podcast. And finally, please listen to the risankizumab important safety considerations next. Thank you all for your time, and thank you for listening.
Risankizumab, a humanized monoclonal antibody to IL-twenty three, is indicated for the treatment of active psoriatic arthritis in adults, and moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Risinkizumab is contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab or any of the excipients. Serious hypersensitivity reactions, including anaphylaxis, may occur. If a serious hypersensitivity reaction occurs, discontinue risankizumab and initiate appropriate therapy immediately. Risankizumab may increase the risk of infections.
Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, discontinue risinkizumab until the infection resolves. Evaluate patients for tuberculosis infection prior to initiating treatment with risankizumab. Avoid use of live vaccines in patients treated with risankizumab. The most common adverse reactions greater than or equal to one percent are upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.
Review accompanying risankizumab full prescribing information for additional information by visiting www.rxabbi.com/pdf/skyrizipi.pdf or contact AbbVie Medical Information at 30110.
