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MADRID – The interleukin-17A inhibitor ixekizumab surpassed the tumor necrosis factor inhibitor adalimumab for treatment of patients with psoriatic arthritis in a multicenter, randomized study with 566 enrolled patients, the first reported results from a head-to-head comparison for this disease of two different classes of biological drugs.
The results showed that a standard, 24-week regimen with each of these agents, both of which already have regulatory approval for treating psoriatic arthritis (PsA), led to achievement of the primary endpoint in 36% of patients treated with ixekizumab (Taltz) and 28% of patients treated with adalimumab (Humira), a statistically significant difference, Philip J. Mease, MD, said at the European Congress of Rheumatology.
“Ixekizumab was superior to adalimumab for improving signs and symptoms of active PsA, as measured by simultaneous achievement of ACR50 [American College of Rheumatology] and PASI 100 [Psoriasis Area and Severity Index],” the study’s primary endpoint that combined a measure of joint disease activity with a measure of skin involvement, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.
This unconventional primary endpoint for testing drugs that treat PsA was called out during discussion of the report for having an inherent bias favoring ixekizumab by its inclusion of a skin outcome that received equal weight with an assessment tool that focused on joint responses. “This was a very unusual primary endpoint that favored ixekizumab,” Roy M. Fleischmann, MD, a Dallas rheumatologist, commented during the discussion.
Dr. Mease readily admitted that the study’s design stacked the deck in favor of ixekizumab, but he added that this decision reflected a desire by the researchers who ran the study to choose a primary endpoint that represented both of the prominent pathologies seen in patients with PsA.
The primary endpoint used in the study “looks at PsA more holistically,” Dr. Mease said in an interview. “It forced clinicians to look beyond just the joints,” in PsA patients. “That has been a limitation of prior PsA treatment assessments,” which until this study have uniformly used single primary outcomes that focus on joint responses, most commonly the ACR20 measure of joint disease activity.
The SPIRIT-H2H (A Study of Ixekizumab [LY2439821] Versus Adalimumab in Participants With Psoriatic Arthritis) study enrolled adults with active PsA who had never before received treatment with a biological drug. Enrolled patients had to have both active disease in their joints and active plaque psoriasis, with an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug. The 566 patients randomized in the study averaged about 48 years old, a bit more than half were men, and patients averaged about 6 years with diagnosed PsA and about 15 years diagnosed with psoriasis. Just over two-thirds of the patients were on concurrent treatment with a conventional synthetic agent, most often methotrexate.
The two components of the primary endpoint each showed the anticipated result. Among the 269 patients treated with adalimumab for the full 24 weeks, 47% had an ACR50 response, as did 51% of the 262 patients who completed their full course of ixekizumab, a between-group difference that was not statistically significant. In contrast, the PASI 100 measure of complete skin resolution occurred in 47% of the adalimumab-treated patients and 60% of those on ixekizumab, a statistically significant difference.
Dr. Mease reported results for several other efficacy measures, and what was notable was statistically significant superiority for ixekizumab in a measure of entheses disease activity, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, which fell to zero in 57% of the ixekizumab patients and 45% of those on adalimumab. “It makes you wonder whether there is something special about interleukin-17 in enthesitis,” Dr. Mease said.
The safety results of the study were consistent with the known adverse effect profiles of both drugs.
The impact of these findings on practice remains to be seen, and will likely depend on both cost considerations as well as clinicians trying to tailor drug choices to individual patients. The relatively new drug, ixekizumab, is consequentially more expensive than the older adalimumab, which has had its price depressed by the recent introduction of a biosimilar agent as well as long-standing competition from multiple TNF inhibitors.
“I think in the United States insurers will continue to steer patients toward whichever drug is cheapest among the highly-effective options,” but this result should lead to more use of interleukin-17 inhibitors as second-line agents for PsA, and it might push some clinicians to prescribe it as the first-line treatment, Dr. Mease said. He was confident that the efficacy profile shown by ixekizumab in SPIRIT-H2H was likely a class effect. Economics aside, the impetus to prescribe ixekizumab or another interleukin-17 inhibitor will be greatest when a patient has more extensive skin involvement, while for patients with little or no skin symptoms clinicians will likely stick with the more established TNF inhibitors as the first drug class to prescribe for PsA.
SPIRIT-H2H was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Mease has been a consultant to, speaker for, and received research funding from Eli Lilly and from several other companies. Dr. Fleischmann has been a consultant to and has received research funding from several companies including Eli Lilly.
SOURCE: Mease PJ et al. Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709.
The results from SPIRIT-H2H confirm with rigorously-collected, prospective data what we had already seen during our routine use of ixekizumab for treating patients with psoriatic arthritis: it does a better job of resolving skin manifestations than any tumor necrosis factor (TNF) inhibitor. For joint symptoms, the two drugs are similar, but for skin ixekizumab has substantial superiority.
I had been hopeful that inhibition of interleukin-17 would surpass TNF inhibition for resolution of joint symptoms, but it looks like they are similar. That’s a little below expectations. But working well for improving skin symptoms is important because it’s something that many patients care about, especially those with more substantial skin symptoms. When matching the best drug to each PsA patient other considerations also exist, such as ease of use. These drugs are delivered by different devices, and ease of administration also matters to patients.
I think it would be premature to presume that the effects shown by ixekizumab extrapolate to all the other interleukin-17 inhibitors. Some of these drugs act via different mechanisms, and so the SPIRIT-H2H results may very well not reflect a class effect.
Thomas Dörner, MD, is professor of rheumatology at Charité University Hospital in Berlin. He has been a consultant to Eli Lilly, as well as to AbbVie, Celgene, Novartis, Pfizer, and Roche, he has been a speaker on behalf of Amgen, Biogen, and Celgene, and he has received research funding from Chugai, Janssen, Roche, and Sanofi. He made these comments in an interview.
The results from SPIRIT-H2H confirm with rigorously-collected, prospective data what we had already seen during our routine use of ixekizumab for treating patients with psoriatic arthritis: it does a better job of resolving skin manifestations than any tumor necrosis factor (TNF) inhibitor. For joint symptoms, the two drugs are similar, but for skin ixekizumab has substantial superiority.
I had been hopeful that inhibition of interleukin-17 would surpass TNF inhibition for resolution of joint symptoms, but it looks like they are similar. That’s a little below expectations. But working well for improving skin symptoms is important because it’s something that many patients care about, especially those with more substantial skin symptoms. When matching the best drug to each PsA patient other considerations also exist, such as ease of use. These drugs are delivered by different devices, and ease of administration also matters to patients.
I think it would be premature to presume that the effects shown by ixekizumab extrapolate to all the other interleukin-17 inhibitors. Some of these drugs act via different mechanisms, and so the SPIRIT-H2H results may very well not reflect a class effect.
Thomas Dörner, MD, is professor of rheumatology at Charité University Hospital in Berlin. He has been a consultant to Eli Lilly, as well as to AbbVie, Celgene, Novartis, Pfizer, and Roche, he has been a speaker on behalf of Amgen, Biogen, and Celgene, and he has received research funding from Chugai, Janssen, Roche, and Sanofi. He made these comments in an interview.
The results from SPIRIT-H2H confirm with rigorously-collected, prospective data what we had already seen during our routine use of ixekizumab for treating patients with psoriatic arthritis: it does a better job of resolving skin manifestations than any tumor necrosis factor (TNF) inhibitor. For joint symptoms, the two drugs are similar, but for skin ixekizumab has substantial superiority.
I had been hopeful that inhibition of interleukin-17 would surpass TNF inhibition for resolution of joint symptoms, but it looks like they are similar. That’s a little below expectations. But working well for improving skin symptoms is important because it’s something that many patients care about, especially those with more substantial skin symptoms. When matching the best drug to each PsA patient other considerations also exist, such as ease of use. These drugs are delivered by different devices, and ease of administration also matters to patients.
I think it would be premature to presume that the effects shown by ixekizumab extrapolate to all the other interleukin-17 inhibitors. Some of these drugs act via different mechanisms, and so the SPIRIT-H2H results may very well not reflect a class effect.
Thomas Dörner, MD, is professor of rheumatology at Charité University Hospital in Berlin. He has been a consultant to Eli Lilly, as well as to AbbVie, Celgene, Novartis, Pfizer, and Roche, he has been a speaker on behalf of Amgen, Biogen, and Celgene, and he has received research funding from Chugai, Janssen, Roche, and Sanofi. He made these comments in an interview.
MADRID – The interleukin-17A inhibitor ixekizumab surpassed the tumor necrosis factor inhibitor adalimumab for treatment of patients with psoriatic arthritis in a multicenter, randomized study with 566 enrolled patients, the first reported results from a head-to-head comparison for this disease of two different classes of biological drugs.
The results showed that a standard, 24-week regimen with each of these agents, both of which already have regulatory approval for treating psoriatic arthritis (PsA), led to achievement of the primary endpoint in 36% of patients treated with ixekizumab (Taltz) and 28% of patients treated with adalimumab (Humira), a statistically significant difference, Philip J. Mease, MD, said at the European Congress of Rheumatology.
“Ixekizumab was superior to adalimumab for improving signs and symptoms of active PsA, as measured by simultaneous achievement of ACR50 [American College of Rheumatology] and PASI 100 [Psoriasis Area and Severity Index],” the study’s primary endpoint that combined a measure of joint disease activity with a measure of skin involvement, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.
This unconventional primary endpoint for testing drugs that treat PsA was called out during discussion of the report for having an inherent bias favoring ixekizumab by its inclusion of a skin outcome that received equal weight with an assessment tool that focused on joint responses. “This was a very unusual primary endpoint that favored ixekizumab,” Roy M. Fleischmann, MD, a Dallas rheumatologist, commented during the discussion.
Dr. Mease readily admitted that the study’s design stacked the deck in favor of ixekizumab, but he added that this decision reflected a desire by the researchers who ran the study to choose a primary endpoint that represented both of the prominent pathologies seen in patients with PsA.
The primary endpoint used in the study “looks at PsA more holistically,” Dr. Mease said in an interview. “It forced clinicians to look beyond just the joints,” in PsA patients. “That has been a limitation of prior PsA treatment assessments,” which until this study have uniformly used single primary outcomes that focus on joint responses, most commonly the ACR20 measure of joint disease activity.
The SPIRIT-H2H (A Study of Ixekizumab [LY2439821] Versus Adalimumab in Participants With Psoriatic Arthritis) study enrolled adults with active PsA who had never before received treatment with a biological drug. Enrolled patients had to have both active disease in their joints and active plaque psoriasis, with an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug. The 566 patients randomized in the study averaged about 48 years old, a bit more than half were men, and patients averaged about 6 years with diagnosed PsA and about 15 years diagnosed with psoriasis. Just over two-thirds of the patients were on concurrent treatment with a conventional synthetic agent, most often methotrexate.
The two components of the primary endpoint each showed the anticipated result. Among the 269 patients treated with adalimumab for the full 24 weeks, 47% had an ACR50 response, as did 51% of the 262 patients who completed their full course of ixekizumab, a between-group difference that was not statistically significant. In contrast, the PASI 100 measure of complete skin resolution occurred in 47% of the adalimumab-treated patients and 60% of those on ixekizumab, a statistically significant difference.
Dr. Mease reported results for several other efficacy measures, and what was notable was statistically significant superiority for ixekizumab in a measure of entheses disease activity, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, which fell to zero in 57% of the ixekizumab patients and 45% of those on adalimumab. “It makes you wonder whether there is something special about interleukin-17 in enthesitis,” Dr. Mease said.
The safety results of the study were consistent with the known adverse effect profiles of both drugs.
The impact of these findings on practice remains to be seen, and will likely depend on both cost considerations as well as clinicians trying to tailor drug choices to individual patients. The relatively new drug, ixekizumab, is consequentially more expensive than the older adalimumab, which has had its price depressed by the recent introduction of a biosimilar agent as well as long-standing competition from multiple TNF inhibitors.
“I think in the United States insurers will continue to steer patients toward whichever drug is cheapest among the highly-effective options,” but this result should lead to more use of interleukin-17 inhibitors as second-line agents for PsA, and it might push some clinicians to prescribe it as the first-line treatment, Dr. Mease said. He was confident that the efficacy profile shown by ixekizumab in SPIRIT-H2H was likely a class effect. Economics aside, the impetus to prescribe ixekizumab or another interleukin-17 inhibitor will be greatest when a patient has more extensive skin involvement, while for patients with little or no skin symptoms clinicians will likely stick with the more established TNF inhibitors as the first drug class to prescribe for PsA.
SPIRIT-H2H was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Mease has been a consultant to, speaker for, and received research funding from Eli Lilly and from several other companies. Dr. Fleischmann has been a consultant to and has received research funding from several companies including Eli Lilly.
SOURCE: Mease PJ et al. Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709.
MADRID – The interleukin-17A inhibitor ixekizumab surpassed the tumor necrosis factor inhibitor adalimumab for treatment of patients with psoriatic arthritis in a multicenter, randomized study with 566 enrolled patients, the first reported results from a head-to-head comparison for this disease of two different classes of biological drugs.
The results showed that a standard, 24-week regimen with each of these agents, both of which already have regulatory approval for treating psoriatic arthritis (PsA), led to achievement of the primary endpoint in 36% of patients treated with ixekizumab (Taltz) and 28% of patients treated with adalimumab (Humira), a statistically significant difference, Philip J. Mease, MD, said at the European Congress of Rheumatology.
“Ixekizumab was superior to adalimumab for improving signs and symptoms of active PsA, as measured by simultaneous achievement of ACR50 [American College of Rheumatology] and PASI 100 [Psoriasis Area and Severity Index],” the study’s primary endpoint that combined a measure of joint disease activity with a measure of skin involvement, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.
This unconventional primary endpoint for testing drugs that treat PsA was called out during discussion of the report for having an inherent bias favoring ixekizumab by its inclusion of a skin outcome that received equal weight with an assessment tool that focused on joint responses. “This was a very unusual primary endpoint that favored ixekizumab,” Roy M. Fleischmann, MD, a Dallas rheumatologist, commented during the discussion.
Dr. Mease readily admitted that the study’s design stacked the deck in favor of ixekizumab, but he added that this decision reflected a desire by the researchers who ran the study to choose a primary endpoint that represented both of the prominent pathologies seen in patients with PsA.
The primary endpoint used in the study “looks at PsA more holistically,” Dr. Mease said in an interview. “It forced clinicians to look beyond just the joints,” in PsA patients. “That has been a limitation of prior PsA treatment assessments,” which until this study have uniformly used single primary outcomes that focus on joint responses, most commonly the ACR20 measure of joint disease activity.
The SPIRIT-H2H (A Study of Ixekizumab [LY2439821] Versus Adalimumab in Participants With Psoriatic Arthritis) study enrolled adults with active PsA who had never before received treatment with a biological drug. Enrolled patients had to have both active disease in their joints and active plaque psoriasis, with an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug. The 566 patients randomized in the study averaged about 48 years old, a bit more than half were men, and patients averaged about 6 years with diagnosed PsA and about 15 years diagnosed with psoriasis. Just over two-thirds of the patients were on concurrent treatment with a conventional synthetic agent, most often methotrexate.
The two components of the primary endpoint each showed the anticipated result. Among the 269 patients treated with adalimumab for the full 24 weeks, 47% had an ACR50 response, as did 51% of the 262 patients who completed their full course of ixekizumab, a between-group difference that was not statistically significant. In contrast, the PASI 100 measure of complete skin resolution occurred in 47% of the adalimumab-treated patients and 60% of those on ixekizumab, a statistically significant difference.
Dr. Mease reported results for several other efficacy measures, and what was notable was statistically significant superiority for ixekizumab in a measure of entheses disease activity, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, which fell to zero in 57% of the ixekizumab patients and 45% of those on adalimumab. “It makes you wonder whether there is something special about interleukin-17 in enthesitis,” Dr. Mease said.
The safety results of the study were consistent with the known adverse effect profiles of both drugs.
The impact of these findings on practice remains to be seen, and will likely depend on both cost considerations as well as clinicians trying to tailor drug choices to individual patients. The relatively new drug, ixekizumab, is consequentially more expensive than the older adalimumab, which has had its price depressed by the recent introduction of a biosimilar agent as well as long-standing competition from multiple TNF inhibitors.
“I think in the United States insurers will continue to steer patients toward whichever drug is cheapest among the highly-effective options,” but this result should lead to more use of interleukin-17 inhibitors as second-line agents for PsA, and it might push some clinicians to prescribe it as the first-line treatment, Dr. Mease said. He was confident that the efficacy profile shown by ixekizumab in SPIRIT-H2H was likely a class effect. Economics aside, the impetus to prescribe ixekizumab or another interleukin-17 inhibitor will be greatest when a patient has more extensive skin involvement, while for patients with little or no skin symptoms clinicians will likely stick with the more established TNF inhibitors as the first drug class to prescribe for PsA.
SPIRIT-H2H was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Mease has been a consultant to, speaker for, and received research funding from Eli Lilly and from several other companies. Dr. Fleischmann has been a consultant to and has received research funding from several companies including Eli Lilly.
SOURCE: Mease PJ et al. Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709.
REPORTING FROM THE EULAR 2019 CONGRESS