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FDA approves infliximab-axxq for numerous indications
The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.
The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.
Full prescribing information can be found on the FDA website, as can more information about biosimilars.
The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.
The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.
Full prescribing information can be found on the FDA website, as can more information about biosimilars.
The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.
The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.
Full prescribing information can be found on the FDA website, as can more information about biosimilars.
Evidence grows for early axSpA treatment, uveitis flare prevention
The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.
We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.
Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.
The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.
We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.
Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.
The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.
We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.
Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.
Certolizumab may reduce uveitis flares, axSpA disease activity
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
Upadacitinib doubles ASAS 40 response vs. placebo in ankylosing spondylitis
ATLANTA – in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.
Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.
Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.
The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.
Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.
SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.
Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.
All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.
“Treatment was generally well tolerated,” she said.
The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.
Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”
AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.
SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.
ATLANTA – in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.
Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.
Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.
The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.
Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.
SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.
Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.
All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.
“Treatment was generally well tolerated,” she said.
The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.
Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”
AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.
SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.
ATLANTA – in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.
Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.
Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.
The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.
Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.
SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.
Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.
All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.
“Treatment was generally well tolerated,” she said.
The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.
Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”
AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.
SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.
REPORTING FROM ACR 2019
More studies like VERVE needed to test live vaccines in special populations
The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.
Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.
Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.
Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
Newer IL-17 inhibitors make their case in phase 3 nonradiographic axial spondyloarthritis trials
A major gap in interleukin-17 inhibitor (IL-17i) therapy for axial spondyloarthritis (axSpA) was evidence of efficacy in nonradiographic axSpA. At ACR 2019, we saw two different IL-17i studies showing efficacy in nr-axSpA patients. Now we know that both secukinumab and ixekizumab are effective in the full spectrum of axSpA patients (ankylosing spondylitis [AS] and nr-axSpA).
The majority of clinicians would consider both AS and nr-axSpA to be driven by common processes and so drugs that are effective on one should have the same effect in the other as well. Hence the results are not a big surprise. In certain places, an approved indication for use may be important especially for reimbursement purposes. These results are likely to have maximal impact there.
The COAST-X study on ixekizumab was designed in a way similar to that of the C-axSpAnd study with certolizumab pegol. There was an extended 52-week placebo arm to study the natural history of nr-axSpA patients who are not actively treated with biologics. This design was necessary to respond to the Food and Drug Administration’s concern that, in the absence of this prolonged observation on placebo, we cannot be sure that nr-axSpA patients are not spontaneously remitting (not due to biologics).
However, the results here did surprise me. Unlike in the C-axSpAnd trial where only 13% of actively treated patients (on certolizumab pegol) switched to open-label treatment, in the COAST-X study 40% of patients on both doses of ixekizumab opted for open-label treatment. The number of patients moving out of the placebo arm was around 60% (similar in both studies). There are no straightforward factors evidently explaining this discrepancy. Between 15% and 25% of patients who switched had achieved the primary endpoint of ASAS40. Does this reflect that ASAS40 is not acceptable to patients? As the results show responses plateaued after week 16, it could be that the patients who switched might have done so well into the 52-week observation period.
Patients in the COAST-X study had slightly longer disease duration and marginally lower HLA-B27 prevalence (both factors may indicate lower chance of treatment response).
The primary endpoint of ASAS40 was met at weeks 16 and 52 with significantly higher rates seen with ixekizumab than with placebo. Again the response seems to plateau around 16 weeks with minimal gain up to week 52.
The results from the secukinumab PREVENT study are very similar to those of the COAST-X study showing the superiority of secukinumab over placebo in treating nr-axSpA patients. Interestingly, if we do not use the loading dose for secukinumab, there does not seem to be any difference from standard treatment with loading. This may have economic and administrative implications on the decision to use loading doses of secukinumab. We should carefully consider the MEASURE 4 trial results before making decisions on the utility of loading doses. In the MEASURE 4 study on AS patients, although there was no difference between load and no load arms of secukinumab (around 60% ASAS20 response in both arms), there was no significant gain above placebo with both doses. (The primary endpoint was not met.) This is likely due to the high placebo response (47% ASAS20 response). Similarly, we see a high placebo response in the COAST-X study as well, with an ASAS40 response rate of about 40% in active secukinumab arms vs. 30% in the placebo arm.
The number of patients dropping out over the 52-week follow-up period was not discussed in the PREVENT trial presentation.
There is not much here to favor one IL-17i over the other.
Dr. Haroon is codirector of the Spondylitis Program at University Health Network and associate professor of medicine and rheumatology at the University of Toronto. He is chair of the scientific committee of the Spondyloarthritis Research and Treatment Network. He disclosed serving as a consultant for Amgen, AbbVie, Janssen, Lilly, Novartis, and UCB.
A major gap in interleukin-17 inhibitor (IL-17i) therapy for axial spondyloarthritis (axSpA) was evidence of efficacy in nonradiographic axSpA. At ACR 2019, we saw two different IL-17i studies showing efficacy in nr-axSpA patients. Now we know that both secukinumab and ixekizumab are effective in the full spectrum of axSpA patients (ankylosing spondylitis [AS] and nr-axSpA).
The majority of clinicians would consider both AS and nr-axSpA to be driven by common processes and so drugs that are effective on one should have the same effect in the other as well. Hence the results are not a big surprise. In certain places, an approved indication for use may be important especially for reimbursement purposes. These results are likely to have maximal impact there.
The COAST-X study on ixekizumab was designed in a way similar to that of the C-axSpAnd study with certolizumab pegol. There was an extended 52-week placebo arm to study the natural history of nr-axSpA patients who are not actively treated with biologics. This design was necessary to respond to the Food and Drug Administration’s concern that, in the absence of this prolonged observation on placebo, we cannot be sure that nr-axSpA patients are not spontaneously remitting (not due to biologics).
However, the results here did surprise me. Unlike in the C-axSpAnd trial where only 13% of actively treated patients (on certolizumab pegol) switched to open-label treatment, in the COAST-X study 40% of patients on both doses of ixekizumab opted for open-label treatment. The number of patients moving out of the placebo arm was around 60% (similar in both studies). There are no straightforward factors evidently explaining this discrepancy. Between 15% and 25% of patients who switched had achieved the primary endpoint of ASAS40. Does this reflect that ASAS40 is not acceptable to patients? As the results show responses plateaued after week 16, it could be that the patients who switched might have done so well into the 52-week observation period.
Patients in the COAST-X study had slightly longer disease duration and marginally lower HLA-B27 prevalence (both factors may indicate lower chance of treatment response).
The primary endpoint of ASAS40 was met at weeks 16 and 52 with significantly higher rates seen with ixekizumab than with placebo. Again the response seems to plateau around 16 weeks with minimal gain up to week 52.
The results from the secukinumab PREVENT study are very similar to those of the COAST-X study showing the superiority of secukinumab over placebo in treating nr-axSpA patients. Interestingly, if we do not use the loading dose for secukinumab, there does not seem to be any difference from standard treatment with loading. This may have economic and administrative implications on the decision to use loading doses of secukinumab. We should carefully consider the MEASURE 4 trial results before making decisions on the utility of loading doses. In the MEASURE 4 study on AS patients, although there was no difference between load and no load arms of secukinumab (around 60% ASAS20 response in both arms), there was no significant gain above placebo with both doses. (The primary endpoint was not met.) This is likely due to the high placebo response (47% ASAS20 response). Similarly, we see a high placebo response in the COAST-X study as well, with an ASAS40 response rate of about 40% in active secukinumab arms vs. 30% in the placebo arm.
The number of patients dropping out over the 52-week follow-up period was not discussed in the PREVENT trial presentation.
There is not much here to favor one IL-17i over the other.
Dr. Haroon is codirector of the Spondylitis Program at University Health Network and associate professor of medicine and rheumatology at the University of Toronto. He is chair of the scientific committee of the Spondyloarthritis Research and Treatment Network. He disclosed serving as a consultant for Amgen, AbbVie, Janssen, Lilly, Novartis, and UCB.
A major gap in interleukin-17 inhibitor (IL-17i) therapy for axial spondyloarthritis (axSpA) was evidence of efficacy in nonradiographic axSpA. At ACR 2019, we saw two different IL-17i studies showing efficacy in nr-axSpA patients. Now we know that both secukinumab and ixekizumab are effective in the full spectrum of axSpA patients (ankylosing spondylitis [AS] and nr-axSpA).
The majority of clinicians would consider both AS and nr-axSpA to be driven by common processes and so drugs that are effective on one should have the same effect in the other as well. Hence the results are not a big surprise. In certain places, an approved indication for use may be important especially for reimbursement purposes. These results are likely to have maximal impact there.
The COAST-X study on ixekizumab was designed in a way similar to that of the C-axSpAnd study with certolizumab pegol. There was an extended 52-week placebo arm to study the natural history of nr-axSpA patients who are not actively treated with biologics. This design was necessary to respond to the Food and Drug Administration’s concern that, in the absence of this prolonged observation on placebo, we cannot be sure that nr-axSpA patients are not spontaneously remitting (not due to biologics).
However, the results here did surprise me. Unlike in the C-axSpAnd trial where only 13% of actively treated patients (on certolizumab pegol) switched to open-label treatment, in the COAST-X study 40% of patients on both doses of ixekizumab opted for open-label treatment. The number of patients moving out of the placebo arm was around 60% (similar in both studies). There are no straightforward factors evidently explaining this discrepancy. Between 15% and 25% of patients who switched had achieved the primary endpoint of ASAS40. Does this reflect that ASAS40 is not acceptable to patients? As the results show responses plateaued after week 16, it could be that the patients who switched might have done so well into the 52-week observation period.
Patients in the COAST-X study had slightly longer disease duration and marginally lower HLA-B27 prevalence (both factors may indicate lower chance of treatment response).
The primary endpoint of ASAS40 was met at weeks 16 and 52 with significantly higher rates seen with ixekizumab than with placebo. Again the response seems to plateau around 16 weeks with minimal gain up to week 52.
The results from the secukinumab PREVENT study are very similar to those of the COAST-X study showing the superiority of secukinumab over placebo in treating nr-axSpA patients. Interestingly, if we do not use the loading dose for secukinumab, there does not seem to be any difference from standard treatment with loading. This may have economic and administrative implications on the decision to use loading doses of secukinumab. We should carefully consider the MEASURE 4 trial results before making decisions on the utility of loading doses. In the MEASURE 4 study on AS patients, although there was no difference between load and no load arms of secukinumab (around 60% ASAS20 response in both arms), there was no significant gain above placebo with both doses. (The primary endpoint was not met.) This is likely due to the high placebo response (47% ASAS20 response). Similarly, we see a high placebo response in the COAST-X study as well, with an ASAS40 response rate of about 40% in active secukinumab arms vs. 30% in the placebo arm.
The number of patients dropping out over the 52-week follow-up period was not discussed in the PREVENT trial presentation.
There is not much here to favor one IL-17i over the other.
Dr. Haroon is codirector of the Spondylitis Program at University Health Network and associate professor of medicine and rheumatology at the University of Toronto. He is chair of the scientific committee of the Spondyloarthritis Research and Treatment Network. He disclosed serving as a consultant for Amgen, AbbVie, Janssen, Lilly, Novartis, and UCB.
COAST-X top-line results: Ixekizumab improves nonradiographic axSpA vs. placebo
ATLANTA – Adding ixekizumab (Taltz) to conventional background medications significantly improved the signs and symptoms of nonradiographic axial spondyloarthritis (axSpA) in the randomized, double-blind, placebo-controlled phase 3 COAST-X trial.
The high-affinity interleukin-17A monoclonal antibody ixekizumab “has shown efficacy in ankylosing spondylitis – also called radiographic axial spondyloarthritis – [and] it recently was approved by the [Food and Drug Administration] for the treatment of active ankylosing spondylitis,” said Atul Deodhar, MD, explaining that COAST-X sought to assess its efficacy in patients with active nonradiographic axSpA and objective evidence of inflammation. He presented the results of the trial at the annual meeting of the American College of Rheumatology.
Of 303 adults with an established diagnosis of axSpA who met Assessment of Spondyloarthritis International Society (ASAS) classification criteria and who were enrolled in the 52-week trial, 105 were randomized to receive background medications plus placebo, and 102 and 96 received background medications plus ixekizumab every 2 or 4 weeks, respectively. The primary endpoint of a 40% improvement in ASAS response criteria (ASAS 40) was reached at week 16 by 19% of the placebo-group patients and by 35% and 40% of the 2- and 4-week ixekizumab-group patients, and at week 52 by 13%, 30%, and 31% of the patients in the groups, respectively, Dr. Deodhar reported.
Additionally, “all major secondary endpoints were met for each ixekizumab regimen, both at week 16 and week 52,” said Dr. Deodhar, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland.
For example, Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 16 declined by 0.6 with placebo, 1.3 with 2-week ixekizumab dosing, and 1.1 points with 4-week ixekizumab dosing; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index changes were –1.5, –2.5, and –2.2, and –1.3, –2.3 and –2.0; Short Form–36 physical component score changes were 5.3, 8.0, and 8.1 points; and MRI sacroiliac joint Spondyloarthritis Research Consortium of Canada score changes were –0.3, –4.5 and –3.4, in the groups, respectively.
“ASDAS less than 2.1 – low disease activity – was achieved by 32% and 27% [in the 2- and 4-week ixekizumab groups] versus 12% in the placebo [group],” he said, noting that similarly significant results were seen at week 52.
Notably, the differences in ASAS 40 response rates between the treatment and placebo groups were observed beginning at week 1, and “a notable proportion” of patients who escaped to the open-label 2-week ixekizumab group, as allowed per study protocol starting at week 16, had an ASAS 40 response at the time of escape; the ASAS 40 response rates at that time were 6.5%, 16.7%, 25% in the groups, respectively, and the rates increased further on open-label ixekizumab, he said.
Study participants were adults diagnosed with axSpA by a physician and treated for at least 3 months. Inclusion criteria also included BASDAI score of at least 4, back pain score of at least 4, inflammation as evidenced by sacroiliitis on MRI or elevated C-reactive protein levels of greater than 5 mg/L, and inadequate response or intolerance to at least two NSAIDs.
Ixekizumab in both treatment groups was given at a dose of 80 mg, and changes to conventional background medications, including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, analgesics, and low-dose corticosteroids, were allowed, as was escape to open-label ixekizumab given every 2 weeks at investigators’ discretion after week 16.
Ixekizumab treatment was well tolerated; the frequency of serious adverse events and AEs leading to treatment discontinuation was low and similar across all arms, Dr. Deodhar said.
For example, treatment-emergent AEs occurred in 55.7%, 77.5%, and 65.6% of patients, serious AEs occurred in 1.0%, 1.0%, and 2.1%, and AE-related discontinuations occurred in 1.9%, 1.0%, and 1.0% or patients in the groups, respectively.
No deaths occurred and no new safety signals were identified.
“The results demonstrate, for the first time, that blocking IL-17A is a potential treatment option for patients with nonradiographic axSpA,” he concluded.
COAST-X was sponsored by Eli Lilly. Dr. Deodhar and most coauthors reported receiving research grants and/or honoraria for consulting or speaking from Eli Lilly and other pharmaceutical companies. Four authors are current employees and shareholders of Eli Lilly.
SOURCE: Deodhar A et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2729.
ATLANTA – Adding ixekizumab (Taltz) to conventional background medications significantly improved the signs and symptoms of nonradiographic axial spondyloarthritis (axSpA) in the randomized, double-blind, placebo-controlled phase 3 COAST-X trial.
The high-affinity interleukin-17A monoclonal antibody ixekizumab “has shown efficacy in ankylosing spondylitis – also called radiographic axial spondyloarthritis – [and] it recently was approved by the [Food and Drug Administration] for the treatment of active ankylosing spondylitis,” said Atul Deodhar, MD, explaining that COAST-X sought to assess its efficacy in patients with active nonradiographic axSpA and objective evidence of inflammation. He presented the results of the trial at the annual meeting of the American College of Rheumatology.
Of 303 adults with an established diagnosis of axSpA who met Assessment of Spondyloarthritis International Society (ASAS) classification criteria and who were enrolled in the 52-week trial, 105 were randomized to receive background medications plus placebo, and 102 and 96 received background medications plus ixekizumab every 2 or 4 weeks, respectively. The primary endpoint of a 40% improvement in ASAS response criteria (ASAS 40) was reached at week 16 by 19% of the placebo-group patients and by 35% and 40% of the 2- and 4-week ixekizumab-group patients, and at week 52 by 13%, 30%, and 31% of the patients in the groups, respectively, Dr. Deodhar reported.
Additionally, “all major secondary endpoints were met for each ixekizumab regimen, both at week 16 and week 52,” said Dr. Deodhar, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland.
For example, Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 16 declined by 0.6 with placebo, 1.3 with 2-week ixekizumab dosing, and 1.1 points with 4-week ixekizumab dosing; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index changes were –1.5, –2.5, and –2.2, and –1.3, –2.3 and –2.0; Short Form–36 physical component score changes were 5.3, 8.0, and 8.1 points; and MRI sacroiliac joint Spondyloarthritis Research Consortium of Canada score changes were –0.3, –4.5 and –3.4, in the groups, respectively.
“ASDAS less than 2.1 – low disease activity – was achieved by 32% and 27% [in the 2- and 4-week ixekizumab groups] versus 12% in the placebo [group],” he said, noting that similarly significant results were seen at week 52.
Notably, the differences in ASAS 40 response rates between the treatment and placebo groups were observed beginning at week 1, and “a notable proportion” of patients who escaped to the open-label 2-week ixekizumab group, as allowed per study protocol starting at week 16, had an ASAS 40 response at the time of escape; the ASAS 40 response rates at that time were 6.5%, 16.7%, 25% in the groups, respectively, and the rates increased further on open-label ixekizumab, he said.
Study participants were adults diagnosed with axSpA by a physician and treated for at least 3 months. Inclusion criteria also included BASDAI score of at least 4, back pain score of at least 4, inflammation as evidenced by sacroiliitis on MRI or elevated C-reactive protein levels of greater than 5 mg/L, and inadequate response or intolerance to at least two NSAIDs.
Ixekizumab in both treatment groups was given at a dose of 80 mg, and changes to conventional background medications, including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, analgesics, and low-dose corticosteroids, were allowed, as was escape to open-label ixekizumab given every 2 weeks at investigators’ discretion after week 16.
Ixekizumab treatment was well tolerated; the frequency of serious adverse events and AEs leading to treatment discontinuation was low and similar across all arms, Dr. Deodhar said.
For example, treatment-emergent AEs occurred in 55.7%, 77.5%, and 65.6% of patients, serious AEs occurred in 1.0%, 1.0%, and 2.1%, and AE-related discontinuations occurred in 1.9%, 1.0%, and 1.0% or patients in the groups, respectively.
No deaths occurred and no new safety signals were identified.
“The results demonstrate, for the first time, that blocking IL-17A is a potential treatment option for patients with nonradiographic axSpA,” he concluded.
COAST-X was sponsored by Eli Lilly. Dr. Deodhar and most coauthors reported receiving research grants and/or honoraria for consulting or speaking from Eli Lilly and other pharmaceutical companies. Four authors are current employees and shareholders of Eli Lilly.
SOURCE: Deodhar A et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2729.
ATLANTA – Adding ixekizumab (Taltz) to conventional background medications significantly improved the signs and symptoms of nonradiographic axial spondyloarthritis (axSpA) in the randomized, double-blind, placebo-controlled phase 3 COAST-X trial.
The high-affinity interleukin-17A monoclonal antibody ixekizumab “has shown efficacy in ankylosing spondylitis – also called radiographic axial spondyloarthritis – [and] it recently was approved by the [Food and Drug Administration] for the treatment of active ankylosing spondylitis,” said Atul Deodhar, MD, explaining that COAST-X sought to assess its efficacy in patients with active nonradiographic axSpA and objective evidence of inflammation. He presented the results of the trial at the annual meeting of the American College of Rheumatology.
Of 303 adults with an established diagnosis of axSpA who met Assessment of Spondyloarthritis International Society (ASAS) classification criteria and who were enrolled in the 52-week trial, 105 were randomized to receive background medications plus placebo, and 102 and 96 received background medications plus ixekizumab every 2 or 4 weeks, respectively. The primary endpoint of a 40% improvement in ASAS response criteria (ASAS 40) was reached at week 16 by 19% of the placebo-group patients and by 35% and 40% of the 2- and 4-week ixekizumab-group patients, and at week 52 by 13%, 30%, and 31% of the patients in the groups, respectively, Dr. Deodhar reported.
Additionally, “all major secondary endpoints were met for each ixekizumab regimen, both at week 16 and week 52,” said Dr. Deodhar, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland.
For example, Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 16 declined by 0.6 with placebo, 1.3 with 2-week ixekizumab dosing, and 1.1 points with 4-week ixekizumab dosing; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index changes were –1.5, –2.5, and –2.2, and –1.3, –2.3 and –2.0; Short Form–36 physical component score changes were 5.3, 8.0, and 8.1 points; and MRI sacroiliac joint Spondyloarthritis Research Consortium of Canada score changes were –0.3, –4.5 and –3.4, in the groups, respectively.
“ASDAS less than 2.1 – low disease activity – was achieved by 32% and 27% [in the 2- and 4-week ixekizumab groups] versus 12% in the placebo [group],” he said, noting that similarly significant results were seen at week 52.
Notably, the differences in ASAS 40 response rates between the treatment and placebo groups were observed beginning at week 1, and “a notable proportion” of patients who escaped to the open-label 2-week ixekizumab group, as allowed per study protocol starting at week 16, had an ASAS 40 response at the time of escape; the ASAS 40 response rates at that time were 6.5%, 16.7%, 25% in the groups, respectively, and the rates increased further on open-label ixekizumab, he said.
Study participants were adults diagnosed with axSpA by a physician and treated for at least 3 months. Inclusion criteria also included BASDAI score of at least 4, back pain score of at least 4, inflammation as evidenced by sacroiliitis on MRI or elevated C-reactive protein levels of greater than 5 mg/L, and inadequate response or intolerance to at least two NSAIDs.
Ixekizumab in both treatment groups was given at a dose of 80 mg, and changes to conventional background medications, including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, analgesics, and low-dose corticosteroids, were allowed, as was escape to open-label ixekizumab given every 2 weeks at investigators’ discretion after week 16.
Ixekizumab treatment was well tolerated; the frequency of serious adverse events and AEs leading to treatment discontinuation was low and similar across all arms, Dr. Deodhar said.
For example, treatment-emergent AEs occurred in 55.7%, 77.5%, and 65.6% of patients, serious AEs occurred in 1.0%, 1.0%, and 2.1%, and AE-related discontinuations occurred in 1.9%, 1.0%, and 1.0% or patients in the groups, respectively.
No deaths occurred and no new safety signals were identified.
“The results demonstrate, for the first time, that blocking IL-17A is a potential treatment option for patients with nonradiographic axSpA,” he concluded.
COAST-X was sponsored by Eli Lilly. Dr. Deodhar and most coauthors reported receiving research grants and/or honoraria for consulting or speaking from Eli Lilly and other pharmaceutical companies. Four authors are current employees and shareholders of Eli Lilly.
SOURCE: Deodhar A et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2729.
REPORTING FROM ACR 2019
FDA announces approval of fifth adalimumab biosimilar, Abrilada
The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.
According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.
Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.
Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”
The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.
According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.
Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.
Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”
The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.
According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.
Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.
Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”
PREVENT trial shows benefits of secukinumab for nonradiographic axSpA
ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.
For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.
“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.
Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.
The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.
At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).
Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).
Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and –1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).
Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.
There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.
Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”
When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.
“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.
The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.
SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.
ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.
For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.
“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.
Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.
The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.
At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).
Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).
Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and –1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).
Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.
There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.
Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”
When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.
“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.
The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.
SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.
ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.
For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.
“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.
Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.
The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.
At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).
Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).
Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and –1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).
Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.
There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.
Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”
When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.
“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.
The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.
SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.
REPORTING FROM ACR 2019
Patients taking TNF inhibitors can safely receive Zostavax
ATLANTA – A group of patients using a tumor necrosis factor inhibitor safely received the live-attenuated varicella vaccine Zostavax without any cases of herpes zoster in the first 6 weeks after vaccination in the blinded, randomized, placebo-controlled Varicella Zoster Vaccine (VERVE) trial .
According to guidelines from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, there is a theoretical concern that patients using a tumor necrosis factor inhibitor (TNFi) and other biologic therapies who receive a live-attenuated version of the varicella vaccine (Zostavax) could become infected with varicella from the vaccine. Patients with RA and psoriatic arthritis as well as other autoimmune and inflammatory conditions who are likely to receive TNFi therapy are also at risk for herpes zoster reactivation, Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology of the University of Alabama at Birmingham, said in his presentation at the annual meeting of the American College of Rheumatology. There also exists a risk for patients receiving low-dose glucocorticoids.
“The challenge, of course, is there’s not a great definition and there certainly is not a well-standardized assay for how immunocompromised someone is, and so that led to the uncertainty in this patient population for this and other live-virus vaccines,” Dr. Curtis said.
Dr. Curtis and colleagues enrolled 627 participants from 33 centers into the VERVE trial. Participants were aged at least 50 years, were taking a TNFi, and had not previously received Zostavax.
Patients in both groups had a mean age of about 63 years and about two-thirds were women. The most common indications for TNFi use in the Zostavax group and the placebo group were RA (59.2% vs. 56.0%, respectively), psoriatic arthritis (24.3% vs. 23.9%), and ankylosing spondylitis (7.2% vs. 8.5%), while the anti-TNF agents used were adalimumab (38.1% vs. 27.4%), infliximab (28.4% vs. 34.2%), etanercept (19.0% vs. 23.5%), golimumab (10.0% vs. 8.1%), and certolizumab pegol (4.5% vs. 6.8%). In addition, some patients in the Zostavax and placebo groups were also taking concomitant therapies with TNFi, such as oral glucocorticoids (9.7% vs. 11.4%).
The researchers randomized participants to receive Zostavax or placebo (saline) and then followed them for 6 weeks, and looked for signs of wild-type or vaccine-strain varicella infection. If participants were suspected to have varicella, they were assessed clinically, underwent polymerase chain reaction testing, and rashes were photographed. At baseline and at 6 weeks, the researchers collected serum and peripheral blood mononuclear cells to determine patient immunity to varicella. After 6 months, participants were unmasked to the treatment arm of the study.
Dr. Curtis and colleagues found no confirmed varicella infection cases at 6 weeks. “To the extent that 0 cases out of 317 vaccinated people is reassuring, there were no cases, so that was exceedingly heartening as a result,” he said.
Out of 20 serious adverse events total in the groups, 15 events occurred before 6 months, including 8 suspected varicella cases in the Zostavax group and 7 in the placebo group. However, there were no positive cases of varicella – either wild type or vaccine type – after polymerase chain reaction tests. Overall, there were 268 adverse events in 195 participants, with 73 events (27.2%) consisting of injection-site reactions. The researchers also found no difference in the rate of disease flares, and found no differences in adverse reactions between groups, apart from a higher rate of injection-site reactions in the varicella group (19.4% vs. 4.2%).
With regard to immunogenicity, the humoral immune response was measured through IgG, which showed an immune response in the varicella group at 6 weeks (geometric mean fold ratio, 1.33; 95% confidence interval, 1.18-1.51), compared with the placebo group (GMFR, 1.02; 95% CI, 0.91-1.14); cell-mediated immune response was measured by interferon-gamma, which also showed an immune response in the live-vaccine group (GMFR, 1.49; 95% CI, 1.14-1.94), compared with participants who received placebo (GMFR, 1.14; 95% CI, 0.87-1.48). In preliminary 1-year data, IgG immune response was elevated in the varicella group (GMFR, 1.46; 95% CI, 1.08-1.99), but there was no elevated immune response for interferon-gamma (GMFR, 0.78; 95% CI, 0.49-1.25).
“I think the trial is encouraging not only for its result with the live zoster vaccine and TNF-treated patients, but also challenge the notion that, if you need to, a live-virus vaccine may in fact be able to be safely given to people with autoimmune and inflammatory diseases, even those treated with biologics like tumor necrosis factor inhibitors,” Dr. Curtis said.
As patients in VERVE consented to long-term follow-up in health plan claims and EHR data, it will be possible to follow these patients in the future to assess herpes zoster reactivation. Dr. Curtis also noted that a new trial involving the recombinant, adjuvanted zoster vaccine (Shingrix) is currently in development and should begin next year.
The VERVE trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis reported serving as a current member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices Herpes Zoster Work Group. He and some of the other authors reported financial relationships with many pharmaceutical companies.
SOURCE: Curtis J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 824.
ATLANTA – A group of patients using a tumor necrosis factor inhibitor safely received the live-attenuated varicella vaccine Zostavax without any cases of herpes zoster in the first 6 weeks after vaccination in the blinded, randomized, placebo-controlled Varicella Zoster Vaccine (VERVE) trial .
According to guidelines from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, there is a theoretical concern that patients using a tumor necrosis factor inhibitor (TNFi) and other biologic therapies who receive a live-attenuated version of the varicella vaccine (Zostavax) could become infected with varicella from the vaccine. Patients with RA and psoriatic arthritis as well as other autoimmune and inflammatory conditions who are likely to receive TNFi therapy are also at risk for herpes zoster reactivation, Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology of the University of Alabama at Birmingham, said in his presentation at the annual meeting of the American College of Rheumatology. There also exists a risk for patients receiving low-dose glucocorticoids.
“The challenge, of course, is there’s not a great definition and there certainly is not a well-standardized assay for how immunocompromised someone is, and so that led to the uncertainty in this patient population for this and other live-virus vaccines,” Dr. Curtis said.
Dr. Curtis and colleagues enrolled 627 participants from 33 centers into the VERVE trial. Participants were aged at least 50 years, were taking a TNFi, and had not previously received Zostavax.
Patients in both groups had a mean age of about 63 years and about two-thirds were women. The most common indications for TNFi use in the Zostavax group and the placebo group were RA (59.2% vs. 56.0%, respectively), psoriatic arthritis (24.3% vs. 23.9%), and ankylosing spondylitis (7.2% vs. 8.5%), while the anti-TNF agents used were adalimumab (38.1% vs. 27.4%), infliximab (28.4% vs. 34.2%), etanercept (19.0% vs. 23.5%), golimumab (10.0% vs. 8.1%), and certolizumab pegol (4.5% vs. 6.8%). In addition, some patients in the Zostavax and placebo groups were also taking concomitant therapies with TNFi, such as oral glucocorticoids (9.7% vs. 11.4%).
The researchers randomized participants to receive Zostavax or placebo (saline) and then followed them for 6 weeks, and looked for signs of wild-type or vaccine-strain varicella infection. If participants were suspected to have varicella, they were assessed clinically, underwent polymerase chain reaction testing, and rashes were photographed. At baseline and at 6 weeks, the researchers collected serum and peripheral blood mononuclear cells to determine patient immunity to varicella. After 6 months, participants were unmasked to the treatment arm of the study.
Dr. Curtis and colleagues found no confirmed varicella infection cases at 6 weeks. “To the extent that 0 cases out of 317 vaccinated people is reassuring, there were no cases, so that was exceedingly heartening as a result,” he said.
Out of 20 serious adverse events total in the groups, 15 events occurred before 6 months, including 8 suspected varicella cases in the Zostavax group and 7 in the placebo group. However, there were no positive cases of varicella – either wild type or vaccine type – after polymerase chain reaction tests. Overall, there were 268 adverse events in 195 participants, with 73 events (27.2%) consisting of injection-site reactions. The researchers also found no difference in the rate of disease flares, and found no differences in adverse reactions between groups, apart from a higher rate of injection-site reactions in the varicella group (19.4% vs. 4.2%).
With regard to immunogenicity, the humoral immune response was measured through IgG, which showed an immune response in the varicella group at 6 weeks (geometric mean fold ratio, 1.33; 95% confidence interval, 1.18-1.51), compared with the placebo group (GMFR, 1.02; 95% CI, 0.91-1.14); cell-mediated immune response was measured by interferon-gamma, which also showed an immune response in the live-vaccine group (GMFR, 1.49; 95% CI, 1.14-1.94), compared with participants who received placebo (GMFR, 1.14; 95% CI, 0.87-1.48). In preliminary 1-year data, IgG immune response was elevated in the varicella group (GMFR, 1.46; 95% CI, 1.08-1.99), but there was no elevated immune response for interferon-gamma (GMFR, 0.78; 95% CI, 0.49-1.25).
“I think the trial is encouraging not only for its result with the live zoster vaccine and TNF-treated patients, but also challenge the notion that, if you need to, a live-virus vaccine may in fact be able to be safely given to people with autoimmune and inflammatory diseases, even those treated with biologics like tumor necrosis factor inhibitors,” Dr. Curtis said.
As patients in VERVE consented to long-term follow-up in health plan claims and EHR data, it will be possible to follow these patients in the future to assess herpes zoster reactivation. Dr. Curtis also noted that a new trial involving the recombinant, adjuvanted zoster vaccine (Shingrix) is currently in development and should begin next year.
The VERVE trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis reported serving as a current member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices Herpes Zoster Work Group. He and some of the other authors reported financial relationships with many pharmaceutical companies.
SOURCE: Curtis J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 824.
ATLANTA – A group of patients using a tumor necrosis factor inhibitor safely received the live-attenuated varicella vaccine Zostavax without any cases of herpes zoster in the first 6 weeks after vaccination in the blinded, randomized, placebo-controlled Varicella Zoster Vaccine (VERVE) trial .
According to guidelines from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, there is a theoretical concern that patients using a tumor necrosis factor inhibitor (TNFi) and other biologic therapies who receive a live-attenuated version of the varicella vaccine (Zostavax) could become infected with varicella from the vaccine. Patients with RA and psoriatic arthritis as well as other autoimmune and inflammatory conditions who are likely to receive TNFi therapy are also at risk for herpes zoster reactivation, Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology of the University of Alabama at Birmingham, said in his presentation at the annual meeting of the American College of Rheumatology. There also exists a risk for patients receiving low-dose glucocorticoids.
“The challenge, of course, is there’s not a great definition and there certainly is not a well-standardized assay for how immunocompromised someone is, and so that led to the uncertainty in this patient population for this and other live-virus vaccines,” Dr. Curtis said.
Dr. Curtis and colleagues enrolled 627 participants from 33 centers into the VERVE trial. Participants were aged at least 50 years, were taking a TNFi, and had not previously received Zostavax.
Patients in both groups had a mean age of about 63 years and about two-thirds were women. The most common indications for TNFi use in the Zostavax group and the placebo group were RA (59.2% vs. 56.0%, respectively), psoriatic arthritis (24.3% vs. 23.9%), and ankylosing spondylitis (7.2% vs. 8.5%), while the anti-TNF agents used were adalimumab (38.1% vs. 27.4%), infliximab (28.4% vs. 34.2%), etanercept (19.0% vs. 23.5%), golimumab (10.0% vs. 8.1%), and certolizumab pegol (4.5% vs. 6.8%). In addition, some patients in the Zostavax and placebo groups were also taking concomitant therapies with TNFi, such as oral glucocorticoids (9.7% vs. 11.4%).
The researchers randomized participants to receive Zostavax or placebo (saline) and then followed them for 6 weeks, and looked for signs of wild-type or vaccine-strain varicella infection. If participants were suspected to have varicella, they were assessed clinically, underwent polymerase chain reaction testing, and rashes were photographed. At baseline and at 6 weeks, the researchers collected serum and peripheral blood mononuclear cells to determine patient immunity to varicella. After 6 months, participants were unmasked to the treatment arm of the study.
Dr. Curtis and colleagues found no confirmed varicella infection cases at 6 weeks. “To the extent that 0 cases out of 317 vaccinated people is reassuring, there were no cases, so that was exceedingly heartening as a result,” he said.
Out of 20 serious adverse events total in the groups, 15 events occurred before 6 months, including 8 suspected varicella cases in the Zostavax group and 7 in the placebo group. However, there were no positive cases of varicella – either wild type or vaccine type – after polymerase chain reaction tests. Overall, there were 268 adverse events in 195 participants, with 73 events (27.2%) consisting of injection-site reactions. The researchers also found no difference in the rate of disease flares, and found no differences in adverse reactions between groups, apart from a higher rate of injection-site reactions in the varicella group (19.4% vs. 4.2%).
With regard to immunogenicity, the humoral immune response was measured through IgG, which showed an immune response in the varicella group at 6 weeks (geometric mean fold ratio, 1.33; 95% confidence interval, 1.18-1.51), compared with the placebo group (GMFR, 1.02; 95% CI, 0.91-1.14); cell-mediated immune response was measured by interferon-gamma, which also showed an immune response in the live-vaccine group (GMFR, 1.49; 95% CI, 1.14-1.94), compared with participants who received placebo (GMFR, 1.14; 95% CI, 0.87-1.48). In preliminary 1-year data, IgG immune response was elevated in the varicella group (GMFR, 1.46; 95% CI, 1.08-1.99), but there was no elevated immune response for interferon-gamma (GMFR, 0.78; 95% CI, 0.49-1.25).
“I think the trial is encouraging not only for its result with the live zoster vaccine and TNF-treated patients, but also challenge the notion that, if you need to, a live-virus vaccine may in fact be able to be safely given to people with autoimmune and inflammatory diseases, even those treated with biologics like tumor necrosis factor inhibitors,” Dr. Curtis said.
As patients in VERVE consented to long-term follow-up in health plan claims and EHR data, it will be possible to follow these patients in the future to assess herpes zoster reactivation. Dr. Curtis also noted that a new trial involving the recombinant, adjuvanted zoster vaccine (Shingrix) is currently in development and should begin next year.
The VERVE trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis reported serving as a current member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices Herpes Zoster Work Group. He and some of the other authors reported financial relationships with many pharmaceutical companies.
SOURCE: Curtis J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 824.
REPORTING FROM ACR 2019