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ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.
When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
C-VIEW
In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.
This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.
The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.
Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.
“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.
Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.
Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.
“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”
AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.
The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.
“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.
C-axSpAnd
In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.
The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.
The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.
For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.
Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.
Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.
Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.
Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.
The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.
“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.
The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.
The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.
SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.
ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.
When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
C-VIEW
In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.
This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.
The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.
Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.
“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.
Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.
Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.
“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”
AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.
The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.
“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.
C-axSpAnd
In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.
The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.
The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.
For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.
Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.
Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.
Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.
Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.
The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.
“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.
The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.
The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.
SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.
ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.
When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
C-VIEW
In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.
This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.
The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.
Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.
“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.
Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.
Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.
“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”
AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.
The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.
“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.
C-axSpAnd
In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.
The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.
The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.
For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.
Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.
Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.
Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.
Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.
The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.
“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.
The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.
The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.
SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.
REPORTING FROM ACR 2019