Label update: Structural damage progression in active PsA Save
Listen to Dr. Catherine Bakewell’s review of clinical data from a recent label update.
Sponsored by Johnson & Johnson Medical Affairs
Transcription
Hello and welcome. I am Doctor. Catherine Bakewell, rheumatologist at Intermountain Health in Salt Lake City, Utah. Welcome to today's podcast where we will discuss the clinical evidence for guselkumab in active psoriatic arthritis or PSA with a particular focus on structural damage. Today's podcast is brought to you by Johnson and Johnson.
I have been compensated by Johnson and Johnson for presentation of this educational information in compliance with FDA requirements applicable to Johnson and Johnson. In this podcast I'll review the APeX data which adds important evidence on radiographic outcomes in adult patients with active psoriatic arthritis and informs a recent label update for guzelkumab. With that in mind, let's turn to the data. As many of you know, guselkumab, a selective interleukin-twenty three inhibitor, was approved for the treatment of active psoriatic arthritis based on the pivotal DISCOVER one and DISCOVER two trials in adult patients. These were large phase three multicenter randomized double blind placebo controlled studies that helped establish the efficacy and safety of guselkumab across key domains of active psoriatic arthritis in adult patients.
Giselcumab was administered subcutaneously in patients with active PSA despite standard therapies, non biologic disease modifying antirheumatic drugs, apremelast, and nonsteroidal anti inflammatory drugs. The primary endpoint in both DISCOVER one and DISCOVER two was ACR 20 response at week twenty four. In DISCOVER one at week twenty four, fifty two percent of patients achieved ACR 20 with guselkumab every eight weeks versus twenty two percent with placebo with a p value less than 0.0001. In DISCOVER two at week twenty four, sixty four percent of patients treated with guselkumab every eight weeks achieved an ACR20 response compared with thirty three percent of patients receiving placebo with a p value less than 0.0001. In addition to an efficacy data analysis through week one hundred, the DISCOVER program helped establish the proven safety of guzelkumab in adult patients with active psoriatic arthritis.
The DISCOVER II trial assessed change from baseline in modified Van der Heide Sharpe score as a major secondary endpoint at week twenty four. While patients receiving guzokumab every eight weeks showed a reduction in structural damage progression, least squares mean change from baseline in total PSA modified Van der Heide Sharp score compared to placebo 0.52 versus 0.95, the results did not reach statistical significance. These results served as the rationale for conducting the APeX trial to build upon the DISCOVER program. With that background, let's move to APeX, a phase 3B study in patients with higher risk of structural damage progression. APeX is an ongoing three year multicenter, randomized, double blind, placebo controlled study evaluating gusaukumab in adults with active psoriatic arthritis.
Patients in the study were biologic naive and had shown an inadequate response to standard therapies such as conventional disease modifying antirheumatic drugs, a premilast, and or nonsteroidal anti inflammatory drugs. Patients with active PSA were also required to have at least two joints with erosions on baseline radiographs of the hands and feet, which helped ensure the study was focused on individuals with active disease and evidence of structural damage involvement. Patients were randomized to receive guselkumab one hundred mg subcutaneously at weeks zero and four followed by every eight week dosing through week one 156 or the placebo regimen during the week zero to week twenty four blinded placebo controlled period. The primary endpoint in APeX is ACR 20 response at week twenty four and the major secondary endpoint is the least squares mean change from baseline in total PSA modified Van der Heide Sharpe score at week twenty four. That design is relevant because it allowed the study not only to evaluate symptom improvement but also to examine whether treatment could slow the progression of structural damage.
Starting with the primary endpoint, the APeX results showed that at week twenty four, sixty eight percent of patients achieved ACR20 with guselkumab Q8 week dosing compared with forty seven percent of patients receiving placebo. This difference was statistically significant with a p value less than 0.001. At week forty eight, seventy four percent of patients achieved ACR20 with cuselkumab q eight week dosing, which was another endpoint in the trial. No statistical testing was conducted after week twenty four in the APeX trial. Now to one of the key parts of the APeX phase 3B study, the radiographic data.
For the major secondary endpoint at week twenty four, patients treated with cuselkumab Q8 week dosing experienced 2.5 times less radiographic progression compared with placebo based on change in the PSA modified Van der Heide Sharpe score. The least squares mean change from week zero, which is baseline, at week twenty four was 0.54 with cuselkumab versus 1.35 with placebo with a p value less than 0.001. This difference at week twenty four was reported as statistically significant, supporting the conclusion that cuselkumab inhibited structural damage progression in adult patients with active PSA with higher risk of structural damage progression. Additionally, the least squares mean change from week twenty four to week forty eight was 0.32 with guselkumab every eight week dosing, which was one of the other endpoints in the trial. Of note, no statistical testing was conducted after week twenty four in the APeX trial.
The APeX dataset also explored key components of structural damage, which were the changes in erosion score and the joint space narrowing, or JSN, score. Both of these were other endpoints in the APeX trial at week twenty four. At week twenty four, the least squares mean change from baseline in erosion score was 0.32 with guselkumab Q eight week dosing compared with 0.87 with placebo. For joint space narrowing, the least squares mean change at week twenty four was 0.24 with guzelkumab Q8 week dosing versus 0.50 with placebo. At week forty eight, the least squares mean change from week twenty four in erosion score was 0.12 with guselkumab Q eight week dosing and the least squares mean change from week twenty four in JSN score was 0.21 with guselkumab q eight week dosing.
Erosion score and JSN score at week twenty four were not adjusted for multiplicity, therefore statistical significance has not been established. As a reminder, no statistical testing was conducted beyond week twenty four in the APeX trial. One of the other endpoints in APeX assessed HAC DI response, which evaluates physical function. HAC DI stands for Health Assessment Questionnaire Disability Index. Among patients with a baseline HAC DI score of at least 0.35, fifty two percent of those treated with cuselkumab every eight weeks achieved a clinically meaningful improvement in HAC DI of 0.35 points or more from baseline at week twenty four compared with forty six percent of patients receiving placebo.
At week forty eight, among patients with a baseline HAC DI score of at least 0.35, sixty percent of those treated with cuselkumab every eight weeks achieved a clinically meaningful improvement in HAC DI of 0.35 points or more from baseline. Again, these data should be interpreted within the statistical framework of the study. HAC DI response at week twenty four was not adjusted for multiplicity so statistical significance was not established and no statistical testing was conducted beyond week 24 in the APeX trial. From a safety perspective, in the placebo controlled period through week twenty four, adverse events were reported in forty two point five percent of patients receiving guselkumab every eight weeks compared with thirty seven point three percent of patients receiving placebo. Serious adverse events were reported in three point one percent of guselkumab treated patients versus in two point six percent of placebo treated patients.
When looking specifically at infections, these were reported in twenty three point five percent of patients receiving guzelkumab and twenty one point zero percent of patients receiving placebo. Serious infections were reported in one point three percent of patients in the guzelkumab group compared with zero point three percent in the placebo group. Through approximately one year, which represents week forty eight, no new safety signals were reported. The overall safety profile observed in patients with active psoriatic arthritis treated with guzelkumab in the APeX trial is consistent with the safety profile observed in the DISCOVER one and DISCOVER two trials. So, what should we take away from the totality of the evidence?
The APeX study expands our understanding of guselkumab in active psoriatic arthritis beyond symptom improvement alone. It shows that in adults with active PSA, particularly those with baseline erosive disease, guselkumab demonstrated significant inhibition of structural damage progression at week twenty four. The APeX trial overall showed joint improvement and inhibition of structural damage progression, which is an important treatment goal for patients with active PSA and their treating healthcare providers. These results are also supported by a proven safety profile through week twenty four. There were no new safety signals reported through week forty eight in the APeX trial.
The overall safety profile observed in adult patients with active psoriatic arthritis treated with guselkumab in the APeX trial is consistent with the safety profile observed in the DISCOVER-one and DISCOVER-two trials. Taken together, these findings add relevant data for guzelkumab as a treatment option for appropriate adult patients with active psoriatic arthritis. Thank you for listening to the ASSET CP585751V1 with us. Before we conclude, let's review the important safety information for guselkumab for psoriatic indications. Indications Tremfya is indicated for the treatment of adults and pediatric patients six years of age and older who also weigh at least forty kilograms with moderate to severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.
Tremfya is indicated for the treatment of adults and pediatric patients six years of age and older who also weigh at least forty kilograms with active psoriatic arthritis. Important safety information: Contraindications. TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients. Warnings and precautions: Hypersensitivity reactions. Serious hypersensitivity reactions, including anaphylaxis, have been reported with post market use of Tremfya.
Some cases require hospitalization. If a serious hypersensitivity reaction occurs, discontinue Tremfya and initiate appropriate therapy. Infections Tremfya may increase the risk of infection. Treatment with Tremfya should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to prescribing Tremfya in patients with a chronic infection or a history of recurrent infection.
Instruct patients receiving Tremfya to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, closely monitor and discontinue Tremfya until the infection resolves. Tuberculosis Tb Evaluate patients for TB infection prior to initiating Tremfya treatment. Do not administer Tremfya to patients with active TB infection. Initiate treatment of latent TB prior to administering Tremfya.
Consider anti TB therapy prior to initiating Tremfya in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor all patients for signs and symptoms of active TB during and after Tremfya treatment. Hepatotoxicity. A serious adverse reaction of drug induced liver injury was reported in a clinical trial subject with Crohn's disease following three doses of a higher than recommended induction regimen. In patients with plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at baseline and periodically thereafter according to routine patient management.
Consider other treatment options in patients with evidence of acute liver disease or cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug induced liver injury. Interrupt treatment if drug induced liver injury is suspected until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. Immunizations Prior to initiating Tremfya, complete all age appropriate vaccinations according to current immunization guidelines.
Avoid use of live vaccines in patients treated with Tremfya. Adverse reactions. Most common adverse reactions associated with Tremfya include plaque psoriasis and psoriatic arthritis adverse reactions greater than or equal to one percent, upper respiratory infections, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections. The safety profile observed in pediatric patients six years of age and older treated with Tremfya up to fifty two weeks was consistent with the safety profile observed in adult patients with moderate to severe plaque psoriasis. The overall safety profile observed in adult patients with psoriatic arthritis is generally consistent with the safety profile in adult patients with plaque psoriasis with the addition of bronchitis and neutrophil count decreased.
Please read the full Prescribing Information and Medication Guide for Tremfya. Provide the medication guide to your patients and encourage discussion. Tremfya is available as a one hundred milligram per ml subcutaneous injection. CP five ten nine seventy five V three.
I have been compensated by Johnson and Johnson for presentation of this educational information in compliance with FDA requirements applicable to Johnson and Johnson. In this podcast I'll review the APeX data which adds important evidence on radiographic outcomes in adult patients with active psoriatic arthritis and informs a recent label update for guzelkumab. With that in mind, let's turn to the data. As many of you know, guselkumab, a selective interleukin-twenty three inhibitor, was approved for the treatment of active psoriatic arthritis based on the pivotal DISCOVER one and DISCOVER two trials in adult patients. These were large phase three multicenter randomized double blind placebo controlled studies that helped establish the efficacy and safety of guselkumab across key domains of active psoriatic arthritis in adult patients.
Giselcumab was administered subcutaneously in patients with active PSA despite standard therapies, non biologic disease modifying antirheumatic drugs, apremelast, and nonsteroidal anti inflammatory drugs. The primary endpoint in both DISCOVER one and DISCOVER two was ACR 20 response at week twenty four. In DISCOVER one at week twenty four, fifty two percent of patients achieved ACR 20 with guselkumab every eight weeks versus twenty two percent with placebo with a p value less than 0.0001. In DISCOVER two at week twenty four, sixty four percent of patients treated with guselkumab every eight weeks achieved an ACR20 response compared with thirty three percent of patients receiving placebo with a p value less than 0.0001. In addition to an efficacy data analysis through week one hundred, the DISCOVER program helped establish the proven safety of guzelkumab in adult patients with active psoriatic arthritis.
The DISCOVER II trial assessed change from baseline in modified Van der Heide Sharpe score as a major secondary endpoint at week twenty four. While patients receiving guzokumab every eight weeks showed a reduction in structural damage progression, least squares mean change from baseline in total PSA modified Van der Heide Sharp score compared to placebo 0.52 versus 0.95, the results did not reach statistical significance. These results served as the rationale for conducting the APeX trial to build upon the DISCOVER program. With that background, let's move to APeX, a phase 3B study in patients with higher risk of structural damage progression. APeX is an ongoing three year multicenter, randomized, double blind, placebo controlled study evaluating gusaukumab in adults with active psoriatic arthritis.
Patients in the study were biologic naive and had shown an inadequate response to standard therapies such as conventional disease modifying antirheumatic drugs, a premilast, and or nonsteroidal anti inflammatory drugs. Patients with active PSA were also required to have at least two joints with erosions on baseline radiographs of the hands and feet, which helped ensure the study was focused on individuals with active disease and evidence of structural damage involvement. Patients were randomized to receive guselkumab one hundred mg subcutaneously at weeks zero and four followed by every eight week dosing through week one 156 or the placebo regimen during the week zero to week twenty four blinded placebo controlled period. The primary endpoint in APeX is ACR 20 response at week twenty four and the major secondary endpoint is the least squares mean change from baseline in total PSA modified Van der Heide Sharpe score at week twenty four. That design is relevant because it allowed the study not only to evaluate symptom improvement but also to examine whether treatment could slow the progression of structural damage.
Starting with the primary endpoint, the APeX results showed that at week twenty four, sixty eight percent of patients achieved ACR20 with guselkumab Q8 week dosing compared with forty seven percent of patients receiving placebo. This difference was statistically significant with a p value less than 0.001. At week forty eight, seventy four percent of patients achieved ACR20 with cuselkumab q eight week dosing, which was another endpoint in the trial. No statistical testing was conducted after week twenty four in the APeX trial. Now to one of the key parts of the APeX phase 3B study, the radiographic data.
For the major secondary endpoint at week twenty four, patients treated with cuselkumab Q8 week dosing experienced 2.5 times less radiographic progression compared with placebo based on change in the PSA modified Van der Heide Sharpe score. The least squares mean change from week zero, which is baseline, at week twenty four was 0.54 with cuselkumab versus 1.35 with placebo with a p value less than 0.001. This difference at week twenty four was reported as statistically significant, supporting the conclusion that cuselkumab inhibited structural damage progression in adult patients with active PSA with higher risk of structural damage progression. Additionally, the least squares mean change from week twenty four to week forty eight was 0.32 with guselkumab every eight week dosing, which was one of the other endpoints in the trial. Of note, no statistical testing was conducted after week twenty four in the APeX trial.
The APeX dataset also explored key components of structural damage, which were the changes in erosion score and the joint space narrowing, or JSN, score. Both of these were other endpoints in the APeX trial at week twenty four. At week twenty four, the least squares mean change from baseline in erosion score was 0.32 with guselkumab Q eight week dosing compared with 0.87 with placebo. For joint space narrowing, the least squares mean change at week twenty four was 0.24 with guzelkumab Q8 week dosing versus 0.50 with placebo. At week forty eight, the least squares mean change from week twenty four in erosion score was 0.12 with guselkumab Q eight week dosing and the least squares mean change from week twenty four in JSN score was 0.21 with guselkumab q eight week dosing.
Erosion score and JSN score at week twenty four were not adjusted for multiplicity, therefore statistical significance has not been established. As a reminder, no statistical testing was conducted beyond week twenty four in the APeX trial. One of the other endpoints in APeX assessed HAC DI response, which evaluates physical function. HAC DI stands for Health Assessment Questionnaire Disability Index. Among patients with a baseline HAC DI score of at least 0.35, fifty two percent of those treated with cuselkumab every eight weeks achieved a clinically meaningful improvement in HAC DI of 0.35 points or more from baseline at week twenty four compared with forty six percent of patients receiving placebo.
At week forty eight, among patients with a baseline HAC DI score of at least 0.35, sixty percent of those treated with cuselkumab every eight weeks achieved a clinically meaningful improvement in HAC DI of 0.35 points or more from baseline. Again, these data should be interpreted within the statistical framework of the study. HAC DI response at week twenty four was not adjusted for multiplicity so statistical significance was not established and no statistical testing was conducted beyond week 24 in the APeX trial. From a safety perspective, in the placebo controlled period through week twenty four, adverse events were reported in forty two point five percent of patients receiving guselkumab every eight weeks compared with thirty seven point three percent of patients receiving placebo. Serious adverse events were reported in three point one percent of guselkumab treated patients versus in two point six percent of placebo treated patients.
When looking specifically at infections, these were reported in twenty three point five percent of patients receiving guzelkumab and twenty one point zero percent of patients receiving placebo. Serious infections were reported in one point three percent of patients in the guzelkumab group compared with zero point three percent in the placebo group. Through approximately one year, which represents week forty eight, no new safety signals were reported. The overall safety profile observed in patients with active psoriatic arthritis treated with guzelkumab in the APeX trial is consistent with the safety profile observed in the DISCOVER one and DISCOVER two trials. So, what should we take away from the totality of the evidence?
The APeX study expands our understanding of guselkumab in active psoriatic arthritis beyond symptom improvement alone. It shows that in adults with active PSA, particularly those with baseline erosive disease, guselkumab demonstrated significant inhibition of structural damage progression at week twenty four. The APeX trial overall showed joint improvement and inhibition of structural damage progression, which is an important treatment goal for patients with active PSA and their treating healthcare providers. These results are also supported by a proven safety profile through week twenty four. There were no new safety signals reported through week forty eight in the APeX trial.
The overall safety profile observed in adult patients with active psoriatic arthritis treated with guselkumab in the APeX trial is consistent with the safety profile observed in the DISCOVER-one and DISCOVER-two trials. Taken together, these findings add relevant data for guzelkumab as a treatment option for appropriate adult patients with active psoriatic arthritis. Thank you for listening to the ASSET CP585751V1 with us. Before we conclude, let's review the important safety information for guselkumab for psoriatic indications. Indications Tremfya is indicated for the treatment of adults and pediatric patients six years of age and older who also weigh at least forty kilograms with moderate to severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.
Tremfya is indicated for the treatment of adults and pediatric patients six years of age and older who also weigh at least forty kilograms with active psoriatic arthritis. Important safety information: Contraindications. TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients. Warnings and precautions: Hypersensitivity reactions. Serious hypersensitivity reactions, including anaphylaxis, have been reported with post market use of Tremfya.
Some cases require hospitalization. If a serious hypersensitivity reaction occurs, discontinue Tremfya and initiate appropriate therapy. Infections Tremfya may increase the risk of infection. Treatment with Tremfya should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to prescribing Tremfya in patients with a chronic infection or a history of recurrent infection.
Instruct patients receiving Tremfya to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, closely monitor and discontinue Tremfya until the infection resolves. Tuberculosis Tb Evaluate patients for TB infection prior to initiating Tremfya treatment. Do not administer Tremfya to patients with active TB infection. Initiate treatment of latent TB prior to administering Tremfya.
Consider anti TB therapy prior to initiating Tremfya in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor all patients for signs and symptoms of active TB during and after Tremfya treatment. Hepatotoxicity. A serious adverse reaction of drug induced liver injury was reported in a clinical trial subject with Crohn's disease following three doses of a higher than recommended induction regimen. In patients with plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at baseline and periodically thereafter according to routine patient management.
Consider other treatment options in patients with evidence of acute liver disease or cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug induced liver injury. Interrupt treatment if drug induced liver injury is suspected until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. Immunizations Prior to initiating Tremfya, complete all age appropriate vaccinations according to current immunization guidelines.
Avoid use of live vaccines in patients treated with Tremfya. Adverse reactions. Most common adverse reactions associated with Tremfya include plaque psoriasis and psoriatic arthritis adverse reactions greater than or equal to one percent, upper respiratory infections, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections. The safety profile observed in pediatric patients six years of age and older treated with Tremfya up to fifty two weeks was consistent with the safety profile observed in adult patients with moderate to severe plaque psoriasis. The overall safety profile observed in adult patients with psoriatic arthritis is generally consistent with the safety profile in adult patients with plaque psoriasis with the addition of bronchitis and neutrophil count decreased.
Please read the full Prescribing Information and Medication Guide for Tremfya. Provide the medication guide to your patients and encourage discussion. Tremfya is available as a one hundred milligram per ml subcutaneous injection. CP five ten nine seventy five V three.
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