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Psoriasis registry study provides more data on infliximab’s infection risk
that led to hospitalization, the use of intravenous antimicrobial therapy, or death, according to a prospective cohort study of cases in the United Kingdom and the Republic of Ireland.
The new data suggest a risk associated with infliximab treatment that previous clinical trials and observational studies were insufficiently powered to detect, according to the investigators, led by Zenas Yiu, of the University of Manchester (England). They found no associations between infection risk and treatment with etanercept, adalimumab, or ustekinumab, and they noted that there are no such data yet on more recently approved biologic therapies for psoriasis, such as secukinumab or ixekizumab.
The British Association of Dermatologists (BAD) recommends infliximab, a tumor necrosis factor (TNF)–blocker, only for severe cases of psoriasis (Psoriasis Area and Severity Index greater than or equal to 20 and a Dermatology Life Quality Index greater than 18), or when other biologics fail or cannot be used.
To address the insufficient power of earlier studies, the researchers used data from the BAD Biologic Interventions Register (BADBIR), a large, prospective psoriasis registry in the United Kingdom and Ireland established in 2007. The analysis included 3,421 subjects in the nonbiologic systemic therapy cohort, and 422 subjects in the all-lines infliximab cohort. The median follow-up period was 1.49 person-years (interquartile range, 2.50 person-years) for the all-lines (not just first-line) infliximab group, and 1.51 person-years (1.84 person-years) for the nonbiologics group.*
Treatment with infliximab was associated with a statistically significant increased risk of serious infection (defined as an infection associated with prolonged hospitalization or use of IV antimicrobial therapy; or an infection that resulted in death), with an adjusted hazard ratio of 1.95 (95% confidence interval, 1.01-3.75), compared with nonbiologic systemic treatments. The risk was higher in the first 6 months (adjusted HR, 3.49; 95% CI, 1.14-10.70), and from 6 months to 1 year (aHR, 2.99; 95% CI, 1.10-8.14,) but did not reach statistical significance at 1 year to 2 years (aHR, 2.03; 95% CI, 0.61-6.79).
There was also an increased risk of serious infection with infliximab compared with methotrexate (aHR, 2.96; 95% CI, 1.58-5.57).
“Given our findings of a higher risk of serious infection associated with infliximab, we provide real-world evidence to reinforce the position of infliximab in the psoriasis treatment hierarchy,” the authors wrote, adding that “patients with severe psoriasis who fulfill the criteria for the prescription of infliximab should be counseled” about the risk of serious infection.
Dr. Yiu disclosed having received nonfinancial support form Novartis, two authors had no disclosures, and the remainder had various disclosures related to pharmaceutical companies. BADBIR is funded by BAD, which receives funding from Pfizer, Janssen Cilag, AbbVie, Novartis, Samsung Bioepis and Eli Lilly for providing pharmacovigilance services.
SOURCE: Yiu ZZN et al. Br J Dermatol. 2018 Aug 2. doi: 10.1111/bjd.17036.
*This article was updated to correctly indicate that the median follow-up period was 1.49 person-years (interquartile range, 2.50 person-years) for the all-lines (not just first-line) infliximab group, and 1.51 person-years (1.84 person-years) for the nonbiologics group.
that led to hospitalization, the use of intravenous antimicrobial therapy, or death, according to a prospective cohort study of cases in the United Kingdom and the Republic of Ireland.
The new data suggest a risk associated with infliximab treatment that previous clinical trials and observational studies were insufficiently powered to detect, according to the investigators, led by Zenas Yiu, of the University of Manchester (England). They found no associations between infection risk and treatment with etanercept, adalimumab, or ustekinumab, and they noted that there are no such data yet on more recently approved biologic therapies for psoriasis, such as secukinumab or ixekizumab.
The British Association of Dermatologists (BAD) recommends infliximab, a tumor necrosis factor (TNF)–blocker, only for severe cases of psoriasis (Psoriasis Area and Severity Index greater than or equal to 20 and a Dermatology Life Quality Index greater than 18), or when other biologics fail or cannot be used.
To address the insufficient power of earlier studies, the researchers used data from the BAD Biologic Interventions Register (BADBIR), a large, prospective psoriasis registry in the United Kingdom and Ireland established in 2007. The analysis included 3,421 subjects in the nonbiologic systemic therapy cohort, and 422 subjects in the all-lines infliximab cohort. The median follow-up period was 1.49 person-years (interquartile range, 2.50 person-years) for the all-lines (not just first-line) infliximab group, and 1.51 person-years (1.84 person-years) for the nonbiologics group.*
Treatment with infliximab was associated with a statistically significant increased risk of serious infection (defined as an infection associated with prolonged hospitalization or use of IV antimicrobial therapy; or an infection that resulted in death), with an adjusted hazard ratio of 1.95 (95% confidence interval, 1.01-3.75), compared with nonbiologic systemic treatments. The risk was higher in the first 6 months (adjusted HR, 3.49; 95% CI, 1.14-10.70), and from 6 months to 1 year (aHR, 2.99; 95% CI, 1.10-8.14,) but did not reach statistical significance at 1 year to 2 years (aHR, 2.03; 95% CI, 0.61-6.79).
There was also an increased risk of serious infection with infliximab compared with methotrexate (aHR, 2.96; 95% CI, 1.58-5.57).
“Given our findings of a higher risk of serious infection associated with infliximab, we provide real-world evidence to reinforce the position of infliximab in the psoriasis treatment hierarchy,” the authors wrote, adding that “patients with severe psoriasis who fulfill the criteria for the prescription of infliximab should be counseled” about the risk of serious infection.
Dr. Yiu disclosed having received nonfinancial support form Novartis, two authors had no disclosures, and the remainder had various disclosures related to pharmaceutical companies. BADBIR is funded by BAD, which receives funding from Pfizer, Janssen Cilag, AbbVie, Novartis, Samsung Bioepis and Eli Lilly for providing pharmacovigilance services.
SOURCE: Yiu ZZN et al. Br J Dermatol. 2018 Aug 2. doi: 10.1111/bjd.17036.
*This article was updated to correctly indicate that the median follow-up period was 1.49 person-years (interquartile range, 2.50 person-years) for the all-lines (not just first-line) infliximab group, and 1.51 person-years (1.84 person-years) for the nonbiologics group.
that led to hospitalization, the use of intravenous antimicrobial therapy, or death, according to a prospective cohort study of cases in the United Kingdom and the Republic of Ireland.
The new data suggest a risk associated with infliximab treatment that previous clinical trials and observational studies were insufficiently powered to detect, according to the investigators, led by Zenas Yiu, of the University of Manchester (England). They found no associations between infection risk and treatment with etanercept, adalimumab, or ustekinumab, and they noted that there are no such data yet on more recently approved biologic therapies for psoriasis, such as secukinumab or ixekizumab.
The British Association of Dermatologists (BAD) recommends infliximab, a tumor necrosis factor (TNF)–blocker, only for severe cases of psoriasis (Psoriasis Area and Severity Index greater than or equal to 20 and a Dermatology Life Quality Index greater than 18), or when other biologics fail or cannot be used.
To address the insufficient power of earlier studies, the researchers used data from the BAD Biologic Interventions Register (BADBIR), a large, prospective psoriasis registry in the United Kingdom and Ireland established in 2007. The analysis included 3,421 subjects in the nonbiologic systemic therapy cohort, and 422 subjects in the all-lines infliximab cohort. The median follow-up period was 1.49 person-years (interquartile range, 2.50 person-years) for the all-lines (not just first-line) infliximab group, and 1.51 person-years (1.84 person-years) for the nonbiologics group.*
Treatment with infliximab was associated with a statistically significant increased risk of serious infection (defined as an infection associated with prolonged hospitalization or use of IV antimicrobial therapy; or an infection that resulted in death), with an adjusted hazard ratio of 1.95 (95% confidence interval, 1.01-3.75), compared with nonbiologic systemic treatments. The risk was higher in the first 6 months (adjusted HR, 3.49; 95% CI, 1.14-10.70), and from 6 months to 1 year (aHR, 2.99; 95% CI, 1.10-8.14,) but did not reach statistical significance at 1 year to 2 years (aHR, 2.03; 95% CI, 0.61-6.79).
There was also an increased risk of serious infection with infliximab compared with methotrexate (aHR, 2.96; 95% CI, 1.58-5.57).
“Given our findings of a higher risk of serious infection associated with infliximab, we provide real-world evidence to reinforce the position of infliximab in the psoriasis treatment hierarchy,” the authors wrote, adding that “patients with severe psoriasis who fulfill the criteria for the prescription of infliximab should be counseled” about the risk of serious infection.
Dr. Yiu disclosed having received nonfinancial support form Novartis, two authors had no disclosures, and the remainder had various disclosures related to pharmaceutical companies. BADBIR is funded by BAD, which receives funding from Pfizer, Janssen Cilag, AbbVie, Novartis, Samsung Bioepis and Eli Lilly for providing pharmacovigilance services.
SOURCE: Yiu ZZN et al. Br J Dermatol. 2018 Aug 2. doi: 10.1111/bjd.17036.
*This article was updated to correctly indicate that the median follow-up period was 1.49 person-years (interquartile range, 2.50 person-years) for the all-lines (not just first-line) infliximab group, and 1.51 person-years (1.84 person-years) for the nonbiologics group.
FROM BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: The study reinforces British guidelines that infliximab should be restricted to most severe cases.
Major finding: Infliximab was associated with a hazard ratio of 1.95 for severe infections, compared with non-biologic systemic therapies.
Study details: Prospective cohort analysis of a psoriasis treatment database of 3,843 individuals.
Disclosures: Dr. Yiu disclosed having received non-financial support form Novartis, two authors had no disclosures, and the remainder had various disclosures related to pharmaceutical companies. BADBIR is funded by BAD, which receives funding from Pfizer, Janssen Cilag, AbbVie, Novartis, Samsung Bioepis and Eli Lilly for providing pharmacovigilance services.
Source: Yiu ZZN et al. Br J Dermatol. 2018 Aug 2. doi: 10.1111/bjd.17036.
AS inflammatory back pain criteria fall short in PsA
Established criteria for identifying inflammatory back pain in people with ankylosing spondylitis do not perform well in identifying axial involvement in people with psoriatic arthritis and neither does clinical judgment, a study shows.
There’s reason to believe that the natural history of patients with psoriatic arthritis (PsA) who have axial disease could differ from those without it, and there are differences in how well criteria that are currently used to identify inflammatory back pain (IBP) in people with ankylosing spondylitis (AS) perform in people with PsA, study first author Kristy S. Yap, MBBS, and her colleagues at the University of Toronto Psoriatic Arthritis Clinic wrote in Annals of the Rheumatic Diseases.
“Axial involvement in PsA is a marker of disease severity, and those with axial disease often have worse outcomes, compared with peripheral arthritis alone,” they wrote.
This is backed up by European League Against Rheumatism recommendations that advise clinicians to consider prescribing tumor necrosis factor inhibitors for people with PsA who have active axial involvement.
“Thus, an important question when evaluating a patient with PsA is to determine if axial PsA is present,” they wrote, noting that it was currently unclear whether the three sets of criteria that exist for defining inflammatory back pain in AS – Calin, Rudwaleit, and Assessment of Spondyloarthritis International Society (ASAS) – were useful for screening for axial involvement in people with PsA.
The researchers therefore set out to determine the agreement between rheumatologist judgment of the presence of IBP as well as the presence of IBP according to the three criteria in 171 patients with PsA (52% male, average age 46.6 years), 96 of whom reported chronic back pain, including 65 with IBP and 31 with nonspecific back pain.
Radiology data from these patients showed that 27 with baseline x-rays fulfilled the New York radiographic criteria for AS, and 45 had radiographic sacroiliitis not satisfying NY criteria (excluding grade 1) and/or syndesmophytes. Nine out of 31 patients with no axial disease on x-ray had evidence of axial disease on MRI. Eighteen out of 54 patients had axial involvement without back pain.
Results showed that agreement (kappa coefficient) between rheumatologist judgment of IBP and IBP criteria in patients with back pain was moderate and was highest for the Calin criteria (0.70; 95% confidence interval, 0.56-0.85), followed by the ASAS criteria (0.61; 95% CI, 0.46-0.76) and the Rudwaleit criteria (0.59; 95% CI, 0.44-0.74).
When x-ray or MRI change was considered “gold standard” for axial involvement for all patients, the specificity was high for rheumatologist judgment of IBP as well as Calin, Rudwaleit, and ASAS criteria, but their sensitivity was low, the researchers reported.
When the investigators compared positive likelihood ratios (LRs) for the presence of back pain, the Rudwaleit criteria (2.17) performed the best in ruling in axial disease, whereas the LRs were 1.75 for Calin and 1.86 for ASAS criteria. Rheumatologist-reported back pain (0.68) performed the best for ruling out axial disease when comparing negative LRs.
“The low positive LRs of the Calin, Rudwaleit, and ASAS criteria as well as that of rheumatologist report of back pain or judgment of IBP for [axial] PsA defined as any axial radiological change found in our study suggests that none of these criteria performed well in detecting axial disease in patients with PsA,” the study authors wrote.
The authors also conducted an exploratory analysis within patients with PsA with back involvement (defined by x-rays or MRI) and compared those with back pain (n = 36) or without (n = 18). The back pain group had a significantly higher Bath Ankylosing Spondylitis Disease Activity Index score (5.72 vs. 4.27), a finding that the authors said they expected because it is a patient-reported measure.
The back pain group also had a lower prevalence of human leukocyte antigen-B*38 (2.78 vs. 27.78), a finding that the authors said was interesting but would need to be replicated in future studies.
The prevalence of HLA-B*27, HLA-B*08, and HLA-C*06 was similar between patients with and without back pain, indicating “that the two groups are largely similar and hence, for the purpose of defining axial disease in PsA, symptoms (back pain) may not be important.”
“The findings of this study suggest that rheumatologist-judged IBP or the criteria for IBP developed for AS may not perform well when ascertaining axial involvement in PsA,” the study authors concluded.
“Moreover, patients with axial radiological changes without back pain were similar to those with back pain. ... In order to stratify patients with poorer prognosis, rheumatologists should consider conducting axial imaging in all patients with PsA regardless of the presence or the nature of back pain,” they added.
The study was funded by the University of Toronto Psoriatic Arthritis Program, which is supported by the Krembil Foundation.
SOURCE: Yap KS et al. Ann Rheum Dis. 2018 Aug 4. doi: 10.1136/annrheumdis-2018-213334.
Identifying psoriatic arthritis with axial disease (AxPsA) is important because it changes the treatment selection and also may be associated with a more severe disease course. In a recent paper by Yap et al, the investigators underscore the challenges in identifying the prevalence of axial disease in PsA. Many of our patients with PsA report back pain at some point in their disease course, and as the rheumatologist, we must grapple with whether their symptoms represent inflammatory disease that requires a change in therapy.
In this study, the authors examined the correlation of three definitions of inflammatory back pain (IBP) with both the rheumatologist’s assessment of whether the patient has IBP and with the presence of imaging findings such as x-ray or MRI abnormalities in the sacroiliac joints or lumbar spine. Of the 171 patients studied, 38% were reported to have IBP per the rheumatologist, 18% were thought to have noninflammatory back pain, and 32% had imaging findings consistent with AxSpA. The agreement between the rheumatologist and the inflammatory back pain criteria was reasonable (kappa 0.6-0.7). Rheumatologists and IBP criteria had moderate sensitivity (0.73-0.82) for having x-ray or MRI changes consistent with axial disease but low specificity (0.33-0.46). Surprisingly, HLA markers were not good markers of having axial disease in this population, aside from HLA-B38, which was protective but relatively uncommon.
The bottom line is that using IBP criteria or our general gestalt is still not as good as getting appropriate imaging and further underscores the potential need to screen patients with PsA, particularly those reporting back pain, for axial involvement.
Alexis R. Ogdie, MD, is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the steering committee for the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Identifying psoriatic arthritis with axial disease (AxPsA) is important because it changes the treatment selection and also may be associated with a more severe disease course. In a recent paper by Yap et al, the investigators underscore the challenges in identifying the prevalence of axial disease in PsA. Many of our patients with PsA report back pain at some point in their disease course, and as the rheumatologist, we must grapple with whether their symptoms represent inflammatory disease that requires a change in therapy.
In this study, the authors examined the correlation of three definitions of inflammatory back pain (IBP) with both the rheumatologist’s assessment of whether the patient has IBP and with the presence of imaging findings such as x-ray or MRI abnormalities in the sacroiliac joints or lumbar spine. Of the 171 patients studied, 38% were reported to have IBP per the rheumatologist, 18% were thought to have noninflammatory back pain, and 32% had imaging findings consistent with AxSpA. The agreement between the rheumatologist and the inflammatory back pain criteria was reasonable (kappa 0.6-0.7). Rheumatologists and IBP criteria had moderate sensitivity (0.73-0.82) for having x-ray or MRI changes consistent with axial disease but low specificity (0.33-0.46). Surprisingly, HLA markers were not good markers of having axial disease in this population, aside from HLA-B38, which was protective but relatively uncommon.
The bottom line is that using IBP criteria or our general gestalt is still not as good as getting appropriate imaging and further underscores the potential need to screen patients with PsA, particularly those reporting back pain, for axial involvement.
Alexis R. Ogdie, MD, is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the steering committee for the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Identifying psoriatic arthritis with axial disease (AxPsA) is important because it changes the treatment selection and also may be associated with a more severe disease course. In a recent paper by Yap et al, the investigators underscore the challenges in identifying the prevalence of axial disease in PsA. Many of our patients with PsA report back pain at some point in their disease course, and as the rheumatologist, we must grapple with whether their symptoms represent inflammatory disease that requires a change in therapy.
In this study, the authors examined the correlation of three definitions of inflammatory back pain (IBP) with both the rheumatologist’s assessment of whether the patient has IBP and with the presence of imaging findings such as x-ray or MRI abnormalities in the sacroiliac joints or lumbar spine. Of the 171 patients studied, 38% were reported to have IBP per the rheumatologist, 18% were thought to have noninflammatory back pain, and 32% had imaging findings consistent with AxSpA. The agreement between the rheumatologist and the inflammatory back pain criteria was reasonable (kappa 0.6-0.7). Rheumatologists and IBP criteria had moderate sensitivity (0.73-0.82) for having x-ray or MRI changes consistent with axial disease but low specificity (0.33-0.46). Surprisingly, HLA markers were not good markers of having axial disease in this population, aside from HLA-B38, which was protective but relatively uncommon.
The bottom line is that using IBP criteria or our general gestalt is still not as good as getting appropriate imaging and further underscores the potential need to screen patients with PsA, particularly those reporting back pain, for axial involvement.
Alexis R. Ogdie, MD, is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the steering committee for the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Established criteria for identifying inflammatory back pain in people with ankylosing spondylitis do not perform well in identifying axial involvement in people with psoriatic arthritis and neither does clinical judgment, a study shows.
There’s reason to believe that the natural history of patients with psoriatic arthritis (PsA) who have axial disease could differ from those without it, and there are differences in how well criteria that are currently used to identify inflammatory back pain (IBP) in people with ankylosing spondylitis (AS) perform in people with PsA, study first author Kristy S. Yap, MBBS, and her colleagues at the University of Toronto Psoriatic Arthritis Clinic wrote in Annals of the Rheumatic Diseases.
“Axial involvement in PsA is a marker of disease severity, and those with axial disease often have worse outcomes, compared with peripheral arthritis alone,” they wrote.
This is backed up by European League Against Rheumatism recommendations that advise clinicians to consider prescribing tumor necrosis factor inhibitors for people with PsA who have active axial involvement.
“Thus, an important question when evaluating a patient with PsA is to determine if axial PsA is present,” they wrote, noting that it was currently unclear whether the three sets of criteria that exist for defining inflammatory back pain in AS – Calin, Rudwaleit, and Assessment of Spondyloarthritis International Society (ASAS) – were useful for screening for axial involvement in people with PsA.
The researchers therefore set out to determine the agreement between rheumatologist judgment of the presence of IBP as well as the presence of IBP according to the three criteria in 171 patients with PsA (52% male, average age 46.6 years), 96 of whom reported chronic back pain, including 65 with IBP and 31 with nonspecific back pain.
Radiology data from these patients showed that 27 with baseline x-rays fulfilled the New York radiographic criteria for AS, and 45 had radiographic sacroiliitis not satisfying NY criteria (excluding grade 1) and/or syndesmophytes. Nine out of 31 patients with no axial disease on x-ray had evidence of axial disease on MRI. Eighteen out of 54 patients had axial involvement without back pain.
Results showed that agreement (kappa coefficient) between rheumatologist judgment of IBP and IBP criteria in patients with back pain was moderate and was highest for the Calin criteria (0.70; 95% confidence interval, 0.56-0.85), followed by the ASAS criteria (0.61; 95% CI, 0.46-0.76) and the Rudwaleit criteria (0.59; 95% CI, 0.44-0.74).
When x-ray or MRI change was considered “gold standard” for axial involvement for all patients, the specificity was high for rheumatologist judgment of IBP as well as Calin, Rudwaleit, and ASAS criteria, but their sensitivity was low, the researchers reported.
When the investigators compared positive likelihood ratios (LRs) for the presence of back pain, the Rudwaleit criteria (2.17) performed the best in ruling in axial disease, whereas the LRs were 1.75 for Calin and 1.86 for ASAS criteria. Rheumatologist-reported back pain (0.68) performed the best for ruling out axial disease when comparing negative LRs.
“The low positive LRs of the Calin, Rudwaleit, and ASAS criteria as well as that of rheumatologist report of back pain or judgment of IBP for [axial] PsA defined as any axial radiological change found in our study suggests that none of these criteria performed well in detecting axial disease in patients with PsA,” the study authors wrote.
The authors also conducted an exploratory analysis within patients with PsA with back involvement (defined by x-rays or MRI) and compared those with back pain (n = 36) or without (n = 18). The back pain group had a significantly higher Bath Ankylosing Spondylitis Disease Activity Index score (5.72 vs. 4.27), a finding that the authors said they expected because it is a patient-reported measure.
The back pain group also had a lower prevalence of human leukocyte antigen-B*38 (2.78 vs. 27.78), a finding that the authors said was interesting but would need to be replicated in future studies.
The prevalence of HLA-B*27, HLA-B*08, and HLA-C*06 was similar between patients with and without back pain, indicating “that the two groups are largely similar and hence, for the purpose of defining axial disease in PsA, symptoms (back pain) may not be important.”
“The findings of this study suggest that rheumatologist-judged IBP or the criteria for IBP developed for AS may not perform well when ascertaining axial involvement in PsA,” the study authors concluded.
“Moreover, patients with axial radiological changes without back pain were similar to those with back pain. ... In order to stratify patients with poorer prognosis, rheumatologists should consider conducting axial imaging in all patients with PsA regardless of the presence or the nature of back pain,” they added.
The study was funded by the University of Toronto Psoriatic Arthritis Program, which is supported by the Krembil Foundation.
SOURCE: Yap KS et al. Ann Rheum Dis. 2018 Aug 4. doi: 10.1136/annrheumdis-2018-213334.
Established criteria for identifying inflammatory back pain in people with ankylosing spondylitis do not perform well in identifying axial involvement in people with psoriatic arthritis and neither does clinical judgment, a study shows.
There’s reason to believe that the natural history of patients with psoriatic arthritis (PsA) who have axial disease could differ from those without it, and there are differences in how well criteria that are currently used to identify inflammatory back pain (IBP) in people with ankylosing spondylitis (AS) perform in people with PsA, study first author Kristy S. Yap, MBBS, and her colleagues at the University of Toronto Psoriatic Arthritis Clinic wrote in Annals of the Rheumatic Diseases.
“Axial involvement in PsA is a marker of disease severity, and those with axial disease often have worse outcomes, compared with peripheral arthritis alone,” they wrote.
This is backed up by European League Against Rheumatism recommendations that advise clinicians to consider prescribing tumor necrosis factor inhibitors for people with PsA who have active axial involvement.
“Thus, an important question when evaluating a patient with PsA is to determine if axial PsA is present,” they wrote, noting that it was currently unclear whether the three sets of criteria that exist for defining inflammatory back pain in AS – Calin, Rudwaleit, and Assessment of Spondyloarthritis International Society (ASAS) – were useful for screening for axial involvement in people with PsA.
The researchers therefore set out to determine the agreement between rheumatologist judgment of the presence of IBP as well as the presence of IBP according to the three criteria in 171 patients with PsA (52% male, average age 46.6 years), 96 of whom reported chronic back pain, including 65 with IBP and 31 with nonspecific back pain.
Radiology data from these patients showed that 27 with baseline x-rays fulfilled the New York radiographic criteria for AS, and 45 had radiographic sacroiliitis not satisfying NY criteria (excluding grade 1) and/or syndesmophytes. Nine out of 31 patients with no axial disease on x-ray had evidence of axial disease on MRI. Eighteen out of 54 patients had axial involvement without back pain.
Results showed that agreement (kappa coefficient) between rheumatologist judgment of IBP and IBP criteria in patients with back pain was moderate and was highest for the Calin criteria (0.70; 95% confidence interval, 0.56-0.85), followed by the ASAS criteria (0.61; 95% CI, 0.46-0.76) and the Rudwaleit criteria (0.59; 95% CI, 0.44-0.74).
When x-ray or MRI change was considered “gold standard” for axial involvement for all patients, the specificity was high for rheumatologist judgment of IBP as well as Calin, Rudwaleit, and ASAS criteria, but their sensitivity was low, the researchers reported.
When the investigators compared positive likelihood ratios (LRs) for the presence of back pain, the Rudwaleit criteria (2.17) performed the best in ruling in axial disease, whereas the LRs were 1.75 for Calin and 1.86 for ASAS criteria. Rheumatologist-reported back pain (0.68) performed the best for ruling out axial disease when comparing negative LRs.
“The low positive LRs of the Calin, Rudwaleit, and ASAS criteria as well as that of rheumatologist report of back pain or judgment of IBP for [axial] PsA defined as any axial radiological change found in our study suggests that none of these criteria performed well in detecting axial disease in patients with PsA,” the study authors wrote.
The authors also conducted an exploratory analysis within patients with PsA with back involvement (defined by x-rays or MRI) and compared those with back pain (n = 36) or without (n = 18). The back pain group had a significantly higher Bath Ankylosing Spondylitis Disease Activity Index score (5.72 vs. 4.27), a finding that the authors said they expected because it is a patient-reported measure.
The back pain group also had a lower prevalence of human leukocyte antigen-B*38 (2.78 vs. 27.78), a finding that the authors said was interesting but would need to be replicated in future studies.
The prevalence of HLA-B*27, HLA-B*08, and HLA-C*06 was similar between patients with and without back pain, indicating “that the two groups are largely similar and hence, for the purpose of defining axial disease in PsA, symptoms (back pain) may not be important.”
“The findings of this study suggest that rheumatologist-judged IBP or the criteria for IBP developed for AS may not perform well when ascertaining axial involvement in PsA,” the study authors concluded.
“Moreover, patients with axial radiological changes without back pain were similar to those with back pain. ... In order to stratify patients with poorer prognosis, rheumatologists should consider conducting axial imaging in all patients with PsA regardless of the presence or the nature of back pain,” they added.
The study was funded by the University of Toronto Psoriatic Arthritis Program, which is supported by the Krembil Foundation.
SOURCE: Yap KS et al. Ann Rheum Dis. 2018 Aug 4. doi: 10.1136/annrheumdis-2018-213334.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Agreement as measured by kappa coefficient between rheumatologist judgment of inflammatory back pain and IBP criteria in patients with back pain was moderate and was highest for the Calin criteria (0.70; 95% confidence interval, 0.56-0.85), followed by the ASAS criteria (0.61; 95% CI, 0.46-0.76) and the Rudwaleit criteria (0.59; 95% CI, 0.44-0.74).
Study details: Prospectively collected data from 171 patients attending a PsA clinic
Disclosures: The study was funded by the University of Toronto Psoriatic Arthritis Program, which is supported by the Krembil Foundation.
Source: Yap KS et al. Ann Rheum Dis. 2018 Aug 4. doi: 10.1136/annrheumdis-2018-213334.
Psoriasis pipeline is full of biologics
CHICAGO – Most psoriasis therapies in the pipeline are biologics, including several interleukin (IL)-23 inhibitors and a promising dual inhibitor of IL-17A and IL-17F, so dermatologists are likely to gain a few more options for treating psoriasis patients who have not responded well to or tolerated existing therapies.
“The IL-23 blockers are ideal for patients who want a few injections,” Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and chair of the department of dermatology of the Mount Sinai Health System, said after the American Academy of Dermatology summer meeting. He discussed clinical trial results for risankizumab, mirikizumab, certolizumab pegol (which was recently approved for psoriasis), bimekizumab, as well as tildrakizumab, which has been approved by the Food and Drug Administration, but has not yet been released.
Tildrakizumab: The FDA approved tildrakizumab (Ilumya), a selective IL-23p19 inhibitor, for treatment of moderate to severe plaque psoriasis in March 2018 based on data from the reSURFACE 1 and reSURFACE 2 trials. After initial doses at weeks 0 and 4, patients received a 100-mg subcutaneous injection dose every 12 weeks. Results of reSURFACE 1 showed that 14% of trial participants achieved a Psoriasis Area and Severity Index (PASI) score of 100 with tildrakizumab at week 12, compared with 1% of those receiving a placebo. Similarly, 35% achieved a PASI 90 and 64% achieved a PASI 75 with the drug, compared with 3% and 6%, respectively, in the placebo group. Findings for reSURFACE 2 were similar; in a pooled analysis, a quarter of the 371 patients reached PASI 100 by week 28, 36% reached PASI 90-PASI 99, 24% reached PASI 75-PASI 89, and 10% reached PASI 50-PASI 74. Efficacy remained high 2 years after treatment, although body weight affected the efficacy. “The authors concluded that PASI and PGA [Physician Global Assessment] responses were numerically greater in patients with lower versus higher body weight,” Dr. Lebwohl said at the meeting.
Tildrakizumab also has an “overall clean safety profile,” he said. Among all patients treated in the trials, the rate of severe infections, malignancies and major adverse cardiac events did not significantly differ from placebo.*
Risankizumab: Also an IL-23 inhibitor, risankizumab, under FDA review for treatment of moderate to severe plaque psoriasis, outperformed both ustekinumab and adalimumab in pivotal phase 3 trials reported in October 2017. In the two ultlMMa trials, 75% of 598 total patients achieved a PASI 90 score after 16 weeks of treatment, compared with 2%-5% of placebo participants and 42%-48% of those on ustekinumab. In ultlMMa-1, just over a third of patients treated with achieved PASI 100, and just over half did in ultlMMa-2, compared with 12% and 24% of those on ustekinumab, respectively.
At 1 year, the proportion of those with PASI 90 rose to 82% in ultlMMa-1 and 81% in ultlMMa-2, with over half the participants achieving PASI 100 in both studies. The risankizumab trial findings were “among highest efficacy results reported to date, with impressive durability of response on and off drug,” Dr. Lebwohl said. “Preliminary safety is encouraging,” but “long-term data are required.”
Mirikizumab: Although not as far along in clinical trials, mirikizumab is another IL-23 inhibitor with “interesting and impressive preliminary results,” Dr. Lebwohl said. In a phase 2 trial of 205 participants whose baseline demographics indicated more severe psoriasis, 67% achieved PASI 90 at week 16 with a 300-mg dose (administered every 8 weeks). Doses of 100 mg and 30 mg resulted in 59% and 29% of participants achieving PASI 90 at week 16.
“The most common treatment emergent adverse events included upper respiratory tract infection [including viral], injection site pain, hypertension and diarrhea,” Dr. Lebwohl said. Patients are now being recruited for two phase 3 studies of mirikizumab (OASIS-1 and OASIS-2).
Certolizumab pegol: Certolizumab pegol is a tumor necrosis factor blocker approved in 2013 for treatment of psoriatic arthritis, and for moderate to severe plaque psoriasis in May 2018. In a pooled data analysis of three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT), 52.3% of participants taking 400 mg subcutaneously every 2 weeks and 44.5% of those taking 200 mg every 2 weeks achieved PASI 90 at week 16, compared with 1.6% of those on placebo. In addition, a trial evaluating maternal transfer of certolizumab to the fetus via placenta found minimal drug concentration levels in the umbilical cord and infant’s plasma. “Certolizumab is ideal for women of childbearing potential,” Dr. Lebwohl said after the meeting.
Bimekizumab: This is a dual inhibitor of IL-17A and IL-17F being studied for treatment of mild psoriasis but “is very promising for psoriatic arthritis, as well as psoriasis,” Dr. Lebwohl said. In the phase 2b BE ABLE 1 trial, up to 79% of patients receiving bimekizumab achieved PASI 90 at week 12, and up to 46% of psoriatic arthritis patients had at least a 50% improvement in joint symptoms, compared with 7% of those on placebo.
Dr. Lebwohl is a consultant for Allergan, Boehringer-Ingelheim, Leo and Promius Pharma, and is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, and ViDac Pharma.
*Correction, 8/6/18: An earlier version of this article misstated the adverse event data for tildrakizumab.
CHICAGO – Most psoriasis therapies in the pipeline are biologics, including several interleukin (IL)-23 inhibitors and a promising dual inhibitor of IL-17A and IL-17F, so dermatologists are likely to gain a few more options for treating psoriasis patients who have not responded well to or tolerated existing therapies.
“The IL-23 blockers are ideal for patients who want a few injections,” Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and chair of the department of dermatology of the Mount Sinai Health System, said after the American Academy of Dermatology summer meeting. He discussed clinical trial results for risankizumab, mirikizumab, certolizumab pegol (which was recently approved for psoriasis), bimekizumab, as well as tildrakizumab, which has been approved by the Food and Drug Administration, but has not yet been released.
Tildrakizumab: The FDA approved tildrakizumab (Ilumya), a selective IL-23p19 inhibitor, for treatment of moderate to severe plaque psoriasis in March 2018 based on data from the reSURFACE 1 and reSURFACE 2 trials. After initial doses at weeks 0 and 4, patients received a 100-mg subcutaneous injection dose every 12 weeks. Results of reSURFACE 1 showed that 14% of trial participants achieved a Psoriasis Area and Severity Index (PASI) score of 100 with tildrakizumab at week 12, compared with 1% of those receiving a placebo. Similarly, 35% achieved a PASI 90 and 64% achieved a PASI 75 with the drug, compared with 3% and 6%, respectively, in the placebo group. Findings for reSURFACE 2 were similar; in a pooled analysis, a quarter of the 371 patients reached PASI 100 by week 28, 36% reached PASI 90-PASI 99, 24% reached PASI 75-PASI 89, and 10% reached PASI 50-PASI 74. Efficacy remained high 2 years after treatment, although body weight affected the efficacy. “The authors concluded that PASI and PGA [Physician Global Assessment] responses were numerically greater in patients with lower versus higher body weight,” Dr. Lebwohl said at the meeting.
Tildrakizumab also has an “overall clean safety profile,” he said. Among all patients treated in the trials, the rate of severe infections, malignancies and major adverse cardiac events did not significantly differ from placebo.*
Risankizumab: Also an IL-23 inhibitor, risankizumab, under FDA review for treatment of moderate to severe plaque psoriasis, outperformed both ustekinumab and adalimumab in pivotal phase 3 trials reported in October 2017. In the two ultlMMa trials, 75% of 598 total patients achieved a PASI 90 score after 16 weeks of treatment, compared with 2%-5% of placebo participants and 42%-48% of those on ustekinumab. In ultlMMa-1, just over a third of patients treated with achieved PASI 100, and just over half did in ultlMMa-2, compared with 12% and 24% of those on ustekinumab, respectively.
At 1 year, the proportion of those with PASI 90 rose to 82% in ultlMMa-1 and 81% in ultlMMa-2, with over half the participants achieving PASI 100 in both studies. The risankizumab trial findings were “among highest efficacy results reported to date, with impressive durability of response on and off drug,” Dr. Lebwohl said. “Preliminary safety is encouraging,” but “long-term data are required.”
Mirikizumab: Although not as far along in clinical trials, mirikizumab is another IL-23 inhibitor with “interesting and impressive preliminary results,” Dr. Lebwohl said. In a phase 2 trial of 205 participants whose baseline demographics indicated more severe psoriasis, 67% achieved PASI 90 at week 16 with a 300-mg dose (administered every 8 weeks). Doses of 100 mg and 30 mg resulted in 59% and 29% of participants achieving PASI 90 at week 16.
“The most common treatment emergent adverse events included upper respiratory tract infection [including viral], injection site pain, hypertension and diarrhea,” Dr. Lebwohl said. Patients are now being recruited for two phase 3 studies of mirikizumab (OASIS-1 and OASIS-2).
Certolizumab pegol: Certolizumab pegol is a tumor necrosis factor blocker approved in 2013 for treatment of psoriatic arthritis, and for moderate to severe plaque psoriasis in May 2018. In a pooled data analysis of three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT), 52.3% of participants taking 400 mg subcutaneously every 2 weeks and 44.5% of those taking 200 mg every 2 weeks achieved PASI 90 at week 16, compared with 1.6% of those on placebo. In addition, a trial evaluating maternal transfer of certolizumab to the fetus via placenta found minimal drug concentration levels in the umbilical cord and infant’s plasma. “Certolizumab is ideal for women of childbearing potential,” Dr. Lebwohl said after the meeting.
Bimekizumab: This is a dual inhibitor of IL-17A and IL-17F being studied for treatment of mild psoriasis but “is very promising for psoriatic arthritis, as well as psoriasis,” Dr. Lebwohl said. In the phase 2b BE ABLE 1 trial, up to 79% of patients receiving bimekizumab achieved PASI 90 at week 12, and up to 46% of psoriatic arthritis patients had at least a 50% improvement in joint symptoms, compared with 7% of those on placebo.
Dr. Lebwohl is a consultant for Allergan, Boehringer-Ingelheim, Leo and Promius Pharma, and is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, and ViDac Pharma.
*Correction, 8/6/18: An earlier version of this article misstated the adverse event data for tildrakizumab.
CHICAGO – Most psoriasis therapies in the pipeline are biologics, including several interleukin (IL)-23 inhibitors and a promising dual inhibitor of IL-17A and IL-17F, so dermatologists are likely to gain a few more options for treating psoriasis patients who have not responded well to or tolerated existing therapies.
“The IL-23 blockers are ideal for patients who want a few injections,” Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and chair of the department of dermatology of the Mount Sinai Health System, said after the American Academy of Dermatology summer meeting. He discussed clinical trial results for risankizumab, mirikizumab, certolizumab pegol (which was recently approved for psoriasis), bimekizumab, as well as tildrakizumab, which has been approved by the Food and Drug Administration, but has not yet been released.
Tildrakizumab: The FDA approved tildrakizumab (Ilumya), a selective IL-23p19 inhibitor, for treatment of moderate to severe plaque psoriasis in March 2018 based on data from the reSURFACE 1 and reSURFACE 2 trials. After initial doses at weeks 0 and 4, patients received a 100-mg subcutaneous injection dose every 12 weeks. Results of reSURFACE 1 showed that 14% of trial participants achieved a Psoriasis Area and Severity Index (PASI) score of 100 with tildrakizumab at week 12, compared with 1% of those receiving a placebo. Similarly, 35% achieved a PASI 90 and 64% achieved a PASI 75 with the drug, compared with 3% and 6%, respectively, in the placebo group. Findings for reSURFACE 2 were similar; in a pooled analysis, a quarter of the 371 patients reached PASI 100 by week 28, 36% reached PASI 90-PASI 99, 24% reached PASI 75-PASI 89, and 10% reached PASI 50-PASI 74. Efficacy remained high 2 years after treatment, although body weight affected the efficacy. “The authors concluded that PASI and PGA [Physician Global Assessment] responses were numerically greater in patients with lower versus higher body weight,” Dr. Lebwohl said at the meeting.
Tildrakizumab also has an “overall clean safety profile,” he said. Among all patients treated in the trials, the rate of severe infections, malignancies and major adverse cardiac events did not significantly differ from placebo.*
Risankizumab: Also an IL-23 inhibitor, risankizumab, under FDA review for treatment of moderate to severe plaque psoriasis, outperformed both ustekinumab and adalimumab in pivotal phase 3 trials reported in October 2017. In the two ultlMMa trials, 75% of 598 total patients achieved a PASI 90 score after 16 weeks of treatment, compared with 2%-5% of placebo participants and 42%-48% of those on ustekinumab. In ultlMMa-1, just over a third of patients treated with achieved PASI 100, and just over half did in ultlMMa-2, compared with 12% and 24% of those on ustekinumab, respectively.
At 1 year, the proportion of those with PASI 90 rose to 82% in ultlMMa-1 and 81% in ultlMMa-2, with over half the participants achieving PASI 100 in both studies. The risankizumab trial findings were “among highest efficacy results reported to date, with impressive durability of response on and off drug,” Dr. Lebwohl said. “Preliminary safety is encouraging,” but “long-term data are required.”
Mirikizumab: Although not as far along in clinical trials, mirikizumab is another IL-23 inhibitor with “interesting and impressive preliminary results,” Dr. Lebwohl said. In a phase 2 trial of 205 participants whose baseline demographics indicated more severe psoriasis, 67% achieved PASI 90 at week 16 with a 300-mg dose (administered every 8 weeks). Doses of 100 mg and 30 mg resulted in 59% and 29% of participants achieving PASI 90 at week 16.
“The most common treatment emergent adverse events included upper respiratory tract infection [including viral], injection site pain, hypertension and diarrhea,” Dr. Lebwohl said. Patients are now being recruited for two phase 3 studies of mirikizumab (OASIS-1 and OASIS-2).
Certolizumab pegol: Certolizumab pegol is a tumor necrosis factor blocker approved in 2013 for treatment of psoriatic arthritis, and for moderate to severe plaque psoriasis in May 2018. In a pooled data analysis of three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT), 52.3% of participants taking 400 mg subcutaneously every 2 weeks and 44.5% of those taking 200 mg every 2 weeks achieved PASI 90 at week 16, compared with 1.6% of those on placebo. In addition, a trial evaluating maternal transfer of certolizumab to the fetus via placenta found minimal drug concentration levels in the umbilical cord and infant’s plasma. “Certolizumab is ideal for women of childbearing potential,” Dr. Lebwohl said after the meeting.
Bimekizumab: This is a dual inhibitor of IL-17A and IL-17F being studied for treatment of mild psoriasis but “is very promising for psoriatic arthritis, as well as psoriasis,” Dr. Lebwohl said. In the phase 2b BE ABLE 1 trial, up to 79% of patients receiving bimekizumab achieved PASI 90 at week 12, and up to 46% of psoriatic arthritis patients had at least a 50% improvement in joint symptoms, compared with 7% of those on placebo.
Dr. Lebwohl is a consultant for Allergan, Boehringer-Ingelheim, Leo and Promius Pharma, and is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, and ViDac Pharma.
*Correction, 8/6/18: An earlier version of this article misstated the adverse event data for tildrakizumab.
EXPERT ANALYSIS FROM SUMMER AAD 2018
FDA announces plan for biosimilar innovation and competition
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Extended data support ixekizumab for plaque psoriasis
followed over a 4-year extension of a randomized trial.
Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.
At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.
A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).
The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.
However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”
The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
followed over a 4-year extension of a randomized trial.
Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.
At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.
A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).
The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.
However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”
The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
followed over a 4-year extension of a randomized trial.
Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.
At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.
A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).
The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.
However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”
The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
FROM JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point: Ixekizumab appears to be an effective option for long-term treatment of patients with moderate to severe psoriasis.
Major finding: A total of 82% of patients achieved PASI 75 at week 208 of the open-label extension study.
Study details: The data come from a 4-year open-label extension of a phase 2 randomized, placebo-controlled trial including 120 adults with psoriasis.
Disclosures: The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
Source: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
Biosimilar switch accepted by most rheumatic disease patients
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
REPORTING FROM BSR 2018
Elderly patients with psoriasis can benefit from biologics with low rates of adverse events
according to a new retrospective study.
Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.
Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.
As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”
To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.
The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.
The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.
Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.
The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.
The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.
The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.
There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.
Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).
None of the authors had financial disclosures, and the study had no funding source.
SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.
according to a new retrospective study.
Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.
Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.
As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”
To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.
The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.
The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.
Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.
The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.
The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.
The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.
There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.
Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).
None of the authors had financial disclosures, and the study had no funding source.
SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.
according to a new retrospective study.
Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.
Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.
As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”
To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.
The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.
The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.
Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.
The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.
The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.
The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.
There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.
Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).
None of the authors had financial disclosures, and the study had no funding source.
SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Key clinical point: Patients aged 65 years and older responded well to biologics and had a low rate of serious adverse events.
Major finding: At 1 year, 65% achieved a PASI 75, 50% achieved a reached PASI 90, and 40% achieved a PASI 100, with a 9.4% rate of serious adverse events.
Study details: The retrospective study comprised 266 patients aged 65 years and older treated with biologics for psoriasis.
Disclosures: None of the authors had financial disclosures, and the study had no funding source.
Source: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018. doi: 10.1111/jdv.15139.
Adalimumab strikes out for aortic inflammation in psoriasis
ORLANDO – Adalimumab (Humira) did not reduce aortic inflammation in a year-long, randomized trial that pitted the tumor necrosis factor (TNF) blocker against phototherapy and placebo in 97 psoriasis patients.
a risk factor for cardiovascular events, said senior investigator Joel M. Gelfand, MD, a dermatology professor at the University of Pennsylvania, Philadelphia.
The other trial, from Canada, also found no effect in the ascending aorta after 52 weeks of treatment, but it did find a modest increase in carotid inflammation (J Invest Dermatol. 2017 Aug;137[8]:1638-45).
Both studies used positron emission tomography/computed tomography to assess vascular inflammation.
“We know patients with psoriasis are at increased risk for cardiovascular disease. We think the same kind of inflammation that occurs in atherosclerosis occurs in psoriasis, but we are still teasing out the impact of therapy and which one is most likely to lower the risk of heart attacks, strokes, and things of that nature,” Dr. Gelfand said at the International Investigative Dermatology meeting. The study was published when he gave his presentation (Circ Cardiovasc Imaging. 2018 Jun. doi: 10.1161/CIRCIMAGING.117.007394).
Although it didn’t reduce aortic inflammation, adalimumab had a positive effect on glycoprotein acetylation, a marker of inflammation and subclinical cardiovascular disease in psoriasis. Observational studies have also reported a drop in cardiovascular events with adalimumab. Taken together, the mixed findings “give us pause for thought,” Dr. Gelfand said.
In a previous trial, he and his colleagues had found that the interleukin blocker ustekinumab (Stelara) reduced aortic inflammation in psoriasis by about 19%, but Dr. Gelfand said at the meeting that it’s too early to opt for ustekinumab over adalimumab for cardiovascular protection: “I don’t think we are quite there yet; we are still not certain.”
Following washout of psoriasis treatments, the 97 subjects were randomized to either adalimumab for 12 months or ultraviolet B phototherapy or placebo for 12 weeks, followed by adalimumab for 12 months.
Aortic inflammation was used as a proxy for cardiovascular events because trials to assess actual event rates would require thousands of patients treated for several years. “They’re not likely to be done in psoriasis any time soon,” Dr. Gelfand said.
At both 12 and 52 weeks, adalimumab patients had no change in aortic inflammation, compared with placebo and baseline. Phototherapy patients had a 4% drop from baseline at 12 weeks, but it was not statistically significant when compared with placebo.
Both adalimumab and phototherapy decreased systemic inflammation as gauged by serum C-reactive protein and interleukin-6 levels, but only adalimumab reduced TNF levels and glycoprotein acetylation at 12 and 52 weeks. Neither treatment affected insulin, adiponectin, or leptin levels. Adalimumab dropped HDL cholesterol a bit, a known side effect, while phototherapy increased it.
About half of the patients in both treatment arms had a 75% reduction in the Psoriasis Area and Severity Index at 12 weeks, compared with 7% of those on placebo. Subjects were aged 43 years, on average, and more than two-thirds were men. They had a mean psoriasis duration of 17 years and a baseline PASI score of 19.
The work was funded by the National Institutes of Health and AbbVie, adalimumab’s maker. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.
SOURCE: Gelfand JM et al. IID 2018, Abstract 393.
ORLANDO – Adalimumab (Humira) did not reduce aortic inflammation in a year-long, randomized trial that pitted the tumor necrosis factor (TNF) blocker against phototherapy and placebo in 97 psoriasis patients.
a risk factor for cardiovascular events, said senior investigator Joel M. Gelfand, MD, a dermatology professor at the University of Pennsylvania, Philadelphia.
The other trial, from Canada, also found no effect in the ascending aorta after 52 weeks of treatment, but it did find a modest increase in carotid inflammation (J Invest Dermatol. 2017 Aug;137[8]:1638-45).
Both studies used positron emission tomography/computed tomography to assess vascular inflammation.
“We know patients with psoriasis are at increased risk for cardiovascular disease. We think the same kind of inflammation that occurs in atherosclerosis occurs in psoriasis, but we are still teasing out the impact of therapy and which one is most likely to lower the risk of heart attacks, strokes, and things of that nature,” Dr. Gelfand said at the International Investigative Dermatology meeting. The study was published when he gave his presentation (Circ Cardiovasc Imaging. 2018 Jun. doi: 10.1161/CIRCIMAGING.117.007394).
Although it didn’t reduce aortic inflammation, adalimumab had a positive effect on glycoprotein acetylation, a marker of inflammation and subclinical cardiovascular disease in psoriasis. Observational studies have also reported a drop in cardiovascular events with adalimumab. Taken together, the mixed findings “give us pause for thought,” Dr. Gelfand said.
In a previous trial, he and his colleagues had found that the interleukin blocker ustekinumab (Stelara) reduced aortic inflammation in psoriasis by about 19%, but Dr. Gelfand said at the meeting that it’s too early to opt for ustekinumab over adalimumab for cardiovascular protection: “I don’t think we are quite there yet; we are still not certain.”
Following washout of psoriasis treatments, the 97 subjects were randomized to either adalimumab for 12 months or ultraviolet B phototherapy or placebo for 12 weeks, followed by adalimumab for 12 months.
Aortic inflammation was used as a proxy for cardiovascular events because trials to assess actual event rates would require thousands of patients treated for several years. “They’re not likely to be done in psoriasis any time soon,” Dr. Gelfand said.
At both 12 and 52 weeks, adalimumab patients had no change in aortic inflammation, compared with placebo and baseline. Phototherapy patients had a 4% drop from baseline at 12 weeks, but it was not statistically significant when compared with placebo.
Both adalimumab and phototherapy decreased systemic inflammation as gauged by serum C-reactive protein and interleukin-6 levels, but only adalimumab reduced TNF levels and glycoprotein acetylation at 12 and 52 weeks. Neither treatment affected insulin, adiponectin, or leptin levels. Adalimumab dropped HDL cholesterol a bit, a known side effect, while phototherapy increased it.
About half of the patients in both treatment arms had a 75% reduction in the Psoriasis Area and Severity Index at 12 weeks, compared with 7% of those on placebo. Subjects were aged 43 years, on average, and more than two-thirds were men. They had a mean psoriasis duration of 17 years and a baseline PASI score of 19.
The work was funded by the National Institutes of Health and AbbVie, adalimumab’s maker. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.
SOURCE: Gelfand JM et al. IID 2018, Abstract 393.
ORLANDO – Adalimumab (Humira) did not reduce aortic inflammation in a year-long, randomized trial that pitted the tumor necrosis factor (TNF) blocker against phototherapy and placebo in 97 psoriasis patients.
a risk factor for cardiovascular events, said senior investigator Joel M. Gelfand, MD, a dermatology professor at the University of Pennsylvania, Philadelphia.
The other trial, from Canada, also found no effect in the ascending aorta after 52 weeks of treatment, but it did find a modest increase in carotid inflammation (J Invest Dermatol. 2017 Aug;137[8]:1638-45).
Both studies used positron emission tomography/computed tomography to assess vascular inflammation.
“We know patients with psoriasis are at increased risk for cardiovascular disease. We think the same kind of inflammation that occurs in atherosclerosis occurs in psoriasis, but we are still teasing out the impact of therapy and which one is most likely to lower the risk of heart attacks, strokes, and things of that nature,” Dr. Gelfand said at the International Investigative Dermatology meeting. The study was published when he gave his presentation (Circ Cardiovasc Imaging. 2018 Jun. doi: 10.1161/CIRCIMAGING.117.007394).
Although it didn’t reduce aortic inflammation, adalimumab had a positive effect on glycoprotein acetylation, a marker of inflammation and subclinical cardiovascular disease in psoriasis. Observational studies have also reported a drop in cardiovascular events with adalimumab. Taken together, the mixed findings “give us pause for thought,” Dr. Gelfand said.
In a previous trial, he and his colleagues had found that the interleukin blocker ustekinumab (Stelara) reduced aortic inflammation in psoriasis by about 19%, but Dr. Gelfand said at the meeting that it’s too early to opt for ustekinumab over adalimumab for cardiovascular protection: “I don’t think we are quite there yet; we are still not certain.”
Following washout of psoriasis treatments, the 97 subjects were randomized to either adalimumab for 12 months or ultraviolet B phototherapy or placebo for 12 weeks, followed by adalimumab for 12 months.
Aortic inflammation was used as a proxy for cardiovascular events because trials to assess actual event rates would require thousands of patients treated for several years. “They’re not likely to be done in psoriasis any time soon,” Dr. Gelfand said.
At both 12 and 52 weeks, adalimumab patients had no change in aortic inflammation, compared with placebo and baseline. Phototherapy patients had a 4% drop from baseline at 12 weeks, but it was not statistically significant when compared with placebo.
Both adalimumab and phototherapy decreased systemic inflammation as gauged by serum C-reactive protein and interleukin-6 levels, but only adalimumab reduced TNF levels and glycoprotein acetylation at 12 and 52 weeks. Neither treatment affected insulin, adiponectin, or leptin levels. Adalimumab dropped HDL cholesterol a bit, a known side effect, while phototherapy increased it.
About half of the patients in both treatment arms had a 75% reduction in the Psoriasis Area and Severity Index at 12 weeks, compared with 7% of those on placebo. Subjects were aged 43 years, on average, and more than two-thirds were men. They had a mean psoriasis duration of 17 years and a baseline PASI score of 19.
The work was funded by the National Institutes of Health and AbbVie, adalimumab’s maker. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.
SOURCE: Gelfand JM et al. IID 2018, Abstract 393.
REPORTING FROM IID 2018
Key clinical point: Adalimumab does not appear to reduce aortic inflammation in psoriasis, a risk factor for cardiovascular events.
Major finding: After a year of treatment, patients had no change in aortic inflammation, compared with placebo and baseline.
Study details: Randomized, controlled trial of 97 patients
Disclosures: The National Institutes of Health and AbbVie, adalimumab’s maker, funded the work. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.
Source: Gelfand JM et al. IID 2018, abstract 393
Checkpoint inhibitors in autoimmune disease: More flares, better cancer outcomes
AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.
“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.
These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.
Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.
With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.
The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.
However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.
Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.
Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.
Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.
“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.
The study was not industry funded. Ms. Tison reported no potential conflicts of interest.
SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.
AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.
“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.
These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.
Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.
With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.
The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.
However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.
Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.
Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.
Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.
“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.
The study was not industry funded. Ms. Tison reported no potential conflicts of interest.
SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.
AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.
“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.
These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.
Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.
With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.
The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.
However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.
Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.
Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.
Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.
“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.
The study was not industry funded. Ms. Tison reported no potential conflicts of interest.
SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: Cancer patients who take a checkpoint inhibitor and have a preexisting autoimmune disease were significantly more likely to have a disease flare but also a better cancer outcome than were those without preexisting disease.
Major finding: In those with a disease flare, progression-free and overall survival were significantly improved (P = .016 and P = .004, respectively).
Study details: Retrospective multicenter study.
Disclosures: The study was not industry funded. Ms. Tison reported no potential conflicts of interest.
Source: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.
Biologic efficacy differs in psoriatic arthritis by lymphocyte phenotype
AMSTERDAM – In patients with psoriatic arthritis (PsA), new evidence suggests selection of biologic disease-modifying antirheumatic drugs (bDMARDs) might be individualized by T-helper cell phenotype to improve disease control, according to the results of a study presented at the European Congress of Rheumatology.
“Our findings suggest a potential for precision medicine in patients with psoriatic arthritis,” reported Ippei Miyagawa, MD, of the University of Occupational and Environmental Health in Kitakyushu, Japan.
These phenotypes were employed to individualize therapy with the currently available targeted bDMARDs. Patients with a Th1-predominant phenotype received ustekinumab (Stelara), which blocks the p40 subunit of interleukin (IL)-12 and IL-23. Patients with a Th17-predominant phenotype received secukinumab (Cosentyx), which targets IL-17. Patients with the Th1/Th17-high phenotype received either secukinumab or a tumor necrosis factor inhibitor. Patients with the Th1/Th17-low phenotype received a TNF inhibitor.
The 26 patients whose bDMARD therapy was individualized were compared with 38 PsA patients who received bDMARDs selected according to EULAR recommendations. The groups were similar for baseline characteristics.
In both groups, there were significant decreases from baseline in essentially all clinical measures, including the Simplified Disease Activity Index, the Psoriasis Area and Severity Index, and the Patient Global Health Assessment. However, several disease markers suggested greater disease control in those receiving individualized therapy. For example, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) at 6 months was 0.76 in the Th17-predominant group versus 1.32 in those on an unselected bDMARD therapy (P = .008).
As a proportion of lymphocytes, Th1-predominant cells greater than 1.2% and Th17-predominant cells greater than 1.5% appeared to be sensitive cutoffs for predicting response to ustekinumab and secukinumab, respectively, according to data presented by Dr. Miyagawa. Although the results in this small series of patients are considered preliminary, Dr. Miyagawa said, “We think that this research is the first step toward the future use of precision medicine in PsA.”
Larger studies are needed to verify that lymphocyte phenotyping is an effective and reproducible strategy for individualizing selection of bDMARDs, but Dr. Miyagawa acknowledged other practical barriers to routine clinical application of this strategy. In particular, he called flow cytometry, which was employed in this study to phenotype lymphocyte expression, “complicated” for routine clinical use. However, this study strongly suggests that lymphocyte expression is a predictor of response to the different bDMARDs now available for treatment of PsA.
“The bDMARDs effective in PsA have different targets and may not offer the same degree of efficacy in all patients. Our study suggests an approach to optimal drug selection,” he said.
The study was not industry funded. Dr. Miyagawa reported no relevant financial disclosures.
SOURCE: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.
AMSTERDAM – In patients with psoriatic arthritis (PsA), new evidence suggests selection of biologic disease-modifying antirheumatic drugs (bDMARDs) might be individualized by T-helper cell phenotype to improve disease control, according to the results of a study presented at the European Congress of Rheumatology.
“Our findings suggest a potential for precision medicine in patients with psoriatic arthritis,” reported Ippei Miyagawa, MD, of the University of Occupational and Environmental Health in Kitakyushu, Japan.
These phenotypes were employed to individualize therapy with the currently available targeted bDMARDs. Patients with a Th1-predominant phenotype received ustekinumab (Stelara), which blocks the p40 subunit of interleukin (IL)-12 and IL-23. Patients with a Th17-predominant phenotype received secukinumab (Cosentyx), which targets IL-17. Patients with the Th1/Th17-high phenotype received either secukinumab or a tumor necrosis factor inhibitor. Patients with the Th1/Th17-low phenotype received a TNF inhibitor.
The 26 patients whose bDMARD therapy was individualized were compared with 38 PsA patients who received bDMARDs selected according to EULAR recommendations. The groups were similar for baseline characteristics.
In both groups, there were significant decreases from baseline in essentially all clinical measures, including the Simplified Disease Activity Index, the Psoriasis Area and Severity Index, and the Patient Global Health Assessment. However, several disease markers suggested greater disease control in those receiving individualized therapy. For example, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) at 6 months was 0.76 in the Th17-predominant group versus 1.32 in those on an unselected bDMARD therapy (P = .008).
As a proportion of lymphocytes, Th1-predominant cells greater than 1.2% and Th17-predominant cells greater than 1.5% appeared to be sensitive cutoffs for predicting response to ustekinumab and secukinumab, respectively, according to data presented by Dr. Miyagawa. Although the results in this small series of patients are considered preliminary, Dr. Miyagawa said, “We think that this research is the first step toward the future use of precision medicine in PsA.”
Larger studies are needed to verify that lymphocyte phenotyping is an effective and reproducible strategy for individualizing selection of bDMARDs, but Dr. Miyagawa acknowledged other practical barriers to routine clinical application of this strategy. In particular, he called flow cytometry, which was employed in this study to phenotype lymphocyte expression, “complicated” for routine clinical use. However, this study strongly suggests that lymphocyte expression is a predictor of response to the different bDMARDs now available for treatment of PsA.
“The bDMARDs effective in PsA have different targets and may not offer the same degree of efficacy in all patients. Our study suggests an approach to optimal drug selection,” he said.
The study was not industry funded. Dr. Miyagawa reported no relevant financial disclosures.
SOURCE: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.
AMSTERDAM – In patients with psoriatic arthritis (PsA), new evidence suggests selection of biologic disease-modifying antirheumatic drugs (bDMARDs) might be individualized by T-helper cell phenotype to improve disease control, according to the results of a study presented at the European Congress of Rheumatology.
“Our findings suggest a potential for precision medicine in patients with psoriatic arthritis,” reported Ippei Miyagawa, MD, of the University of Occupational and Environmental Health in Kitakyushu, Japan.
These phenotypes were employed to individualize therapy with the currently available targeted bDMARDs. Patients with a Th1-predominant phenotype received ustekinumab (Stelara), which blocks the p40 subunit of interleukin (IL)-12 and IL-23. Patients with a Th17-predominant phenotype received secukinumab (Cosentyx), which targets IL-17. Patients with the Th1/Th17-high phenotype received either secukinumab or a tumor necrosis factor inhibitor. Patients with the Th1/Th17-low phenotype received a TNF inhibitor.
The 26 patients whose bDMARD therapy was individualized were compared with 38 PsA patients who received bDMARDs selected according to EULAR recommendations. The groups were similar for baseline characteristics.
In both groups, there were significant decreases from baseline in essentially all clinical measures, including the Simplified Disease Activity Index, the Psoriasis Area and Severity Index, and the Patient Global Health Assessment. However, several disease markers suggested greater disease control in those receiving individualized therapy. For example, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) at 6 months was 0.76 in the Th17-predominant group versus 1.32 in those on an unselected bDMARD therapy (P = .008).
As a proportion of lymphocytes, Th1-predominant cells greater than 1.2% and Th17-predominant cells greater than 1.5% appeared to be sensitive cutoffs for predicting response to ustekinumab and secukinumab, respectively, according to data presented by Dr. Miyagawa. Although the results in this small series of patients are considered preliminary, Dr. Miyagawa said, “We think that this research is the first step toward the future use of precision medicine in PsA.”
Larger studies are needed to verify that lymphocyte phenotyping is an effective and reproducible strategy for individualizing selection of bDMARDs, but Dr. Miyagawa acknowledged other practical barriers to routine clinical application of this strategy. In particular, he called flow cytometry, which was employed in this study to phenotype lymphocyte expression, “complicated” for routine clinical use. However, this study strongly suggests that lymphocyte expression is a predictor of response to the different bDMARDs now available for treatment of PsA.
“The bDMARDs effective in PsA have different targets and may not offer the same degree of efficacy in all patients. Our study suggests an approach to optimal drug selection,” he said.
The study was not industry funded. Dr. Miyagawa reported no relevant financial disclosures.
SOURCE: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: Lymphocyte profile phenotypes appear to permit individualized biologic therapy in patients with PsA.
Major finding: Therapy individualized for Th17-predominant PsA produced a DAS28 score 0.56 points lower than did nonselected therapy (P = .008).
Study details: A prospective, nonrandomized study of 64 PsA patients with either individualized bDMARD therapy or bDMARDs selected according to EULAR recommendations.
Disclosures: The study was not industry funded. Dr. Miyagawa reported no relevant financial disclosures.
Source: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.