Ankylosing spondylitis

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, 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.

[email protected]

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, 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.

[email protected]

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, 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.

[email protected]

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

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.

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.

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.

Sharon Worcester/MDedge News

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.

[email protected]

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.

Sharon Worcester/MDedge News

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.

[email protected]

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.

Sharon Worcester/MDedge News

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.

[email protected]

SOURCE: Deodhar A et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2729.

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.

Olivier Le Moal/Getty Images

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.”

[email protected]

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.

Olivier Le Moal/Getty Images

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.”

[email protected]

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.

Olivier Le Moal/Getty Images

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.”

[email protected]

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.

Jeff Craven/MDedge News

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.

Jeff Craven/MDedge News

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.

Jeff Craven/MDedge News

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 – 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.

Patients with ankylosing spondylitis who are male, have evidence of spinal damage, or have higher levels of inflammatory markers may be at higher risk of disease progression, a study has found.

“Assessment of AS-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors,” Ismail Sari, MD, of the University of Toronto and coauthors wrote in Arthritis Care & Research. “This could help identify the mechanisms responsible for progression and thereby personalizing treatment.”

The researchers found that nearly one-quarter (24.3%) of 350 individuals with ankylosing spondylitis in a longitudinal cohort study showed radiographic evidence of progression, defined as a change of 2 units on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in 2 years. Overall, 76% of the group were males, and the group had a mean age of about 38 years with a mean symptom duration of nearly 15 years.

Over the 6-year follow-up, the mean mSASSS increased from 9.3 units at baseline to 17.7 units, with more progression seen in the cervical spine than the lumbar segments. During the first 2 years, the total mSASSS increased by a mean of 1.23 units; in years 2-4, it increased by a mean of 1.47 units, and from 4 to 6 years, it increased by a mean of 1.52 units.

Male sex was associated with more than double the risk of radiographic progression (hazard ratio, 2.46; 95% confidence interval, 1.05-5.76), while individuals with radiographic evidence of spinal damage at baseline had a nearly eightfold higher risk of progression (HR, 7.98; 95% CI, 3.98-16). The risk for disease progression also increased with higher levels of C-reactive protein.

The investigators also found that patients who had used tumor necrosis factor inhibitor therapy for at least 1 year had an 18% reduction in the rate of spinal progression.

However, other factors including symptom duration, presence of HLA-B27, smoking status, presence of radiographic hip disease, or use of disease-modifying antirheumatic drugs or NSAIDs did not appear to influence the risk of disease progression.

No funding or conflicts of interest were declared.

SOURCE: Sari I et al. Arthritis Care Res. 2019 Nov 1. doi: 10.1002/acr.24104.

Patients with ankylosing spondylitis who are male, have evidence of spinal damage, or have higher levels of inflammatory markers may be at higher risk of disease progression, a study has found.

“Assessment of AS-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors,” Ismail Sari, MD, of the University of Toronto and coauthors wrote in Arthritis Care & Research. “This could help identify the mechanisms responsible for progression and thereby personalizing treatment.”

The researchers found that nearly one-quarter (24.3%) of 350 individuals with ankylosing spondylitis in a longitudinal cohort study showed radiographic evidence of progression, defined as a change of 2 units on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in 2 years. Overall, 76% of the group were males, and the group had a mean age of about 38 years with a mean symptom duration of nearly 15 years.

Over the 6-year follow-up, the mean mSASSS increased from 9.3 units at baseline to 17.7 units, with more progression seen in the cervical spine than the lumbar segments. During the first 2 years, the total mSASSS increased by a mean of 1.23 units; in years 2-4, it increased by a mean of 1.47 units, and from 4 to 6 years, it increased by a mean of 1.52 units.

Male sex was associated with more than double the risk of radiographic progression (hazard ratio, 2.46; 95% confidence interval, 1.05-5.76), while individuals with radiographic evidence of spinal damage at baseline had a nearly eightfold higher risk of progression (HR, 7.98; 95% CI, 3.98-16). The risk for disease progression also increased with higher levels of C-reactive protein.

The investigators also found that patients who had used tumor necrosis factor inhibitor therapy for at least 1 year had an 18% reduction in the rate of spinal progression.

However, other factors including symptom duration, presence of HLA-B27, smoking status, presence of radiographic hip disease, or use of disease-modifying antirheumatic drugs or NSAIDs did not appear to influence the risk of disease progression.

No funding or conflicts of interest were declared.

SOURCE: Sari I et al. Arthritis Care Res. 2019 Nov 1. doi: 10.1002/acr.24104.

Patients with ankylosing spondylitis who are male, have evidence of spinal damage, or have higher levels of inflammatory markers may be at higher risk of disease progression, a study has found.

“Assessment of AS-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors,” Ismail Sari, MD, of the University of Toronto and coauthors wrote in Arthritis Care & Research. “This could help identify the mechanisms responsible for progression and thereby personalizing treatment.”

The researchers found that nearly one-quarter (24.3%) of 350 individuals with ankylosing spondylitis in a longitudinal cohort study showed radiographic evidence of progression, defined as a change of 2 units on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in 2 years. Overall, 76% of the group were males, and the group had a mean age of about 38 years with a mean symptom duration of nearly 15 years.

Over the 6-year follow-up, the mean mSASSS increased from 9.3 units at baseline to 17.7 units, with more progression seen in the cervical spine than the lumbar segments. During the first 2 years, the total mSASSS increased by a mean of 1.23 units; in years 2-4, it increased by a mean of 1.47 units, and from 4 to 6 years, it increased by a mean of 1.52 units.

Male sex was associated with more than double the risk of radiographic progression (hazard ratio, 2.46; 95% confidence interval, 1.05-5.76), while individuals with radiographic evidence of spinal damage at baseline had a nearly eightfold higher risk of progression (HR, 7.98; 95% CI, 3.98-16). The risk for disease progression also increased with higher levels of C-reactive protein.

The investigators also found that patients who had used tumor necrosis factor inhibitor therapy for at least 1 year had an 18% reduction in the rate of spinal progression.

However, other factors including symptom duration, presence of HLA-B27, smoking status, presence of radiographic hip disease, or use of disease-modifying antirheumatic drugs or NSAIDs did not appear to influence the risk of disease progression.

No funding or conflicts of interest were declared.

SOURCE: Sari I et al. Arthritis Care Res. 2019 Nov 1. doi: 10.1002/acr.24104.

Three international clinical trials in Europe are examining the effectiveness of treat-to-target (T2T) therapeutic regimens in patients with axial spondyloarthritis (axSpA), including two that will be the first randomized trial evidence to support or refute the T2T strategy for patients ranging from those with nonradiographic disease to patients with ankylosing spondylitis.

T2T has proved before to work in patients with rheumatoid arthritis and psoriatic arthritis with evidence from the TICORA (Tight Control of Rheumatoid Arthritis) and TICOPA (Tight Control in Psoriatic Arthritis) trials.

Two T2T trials in axSpA are still in the recruiting phase, and one has completed enrollment, with no results available yet.
 

Tight control in spondyloarthritis (TICOSPA)

TICOSPA is a 1-year, ongoing, multinational, cluster-randomized, prospective cohort study that has enrolled 163 patients with a diagnosis of active axial spondyloarthritis to evaluate the potential benefit of a T2T strategy in which the rheumatologist will agree to monitor very closely – at least every 4 weeks – and treat patients in accordance with a predefined strategy. The T2T strategy is compared with usual care as given by the treating rheumatologist. Prior to the trial, patients were on nonoptimal NSAID treatment.

“Tight control” in this study refers to the time from treatment initiation to adequate assessment of efficacy and safety, which for efficacy should be at 2-4 weeks for NSAIDs and 12-16 weeks for tumor necrosis factor inhibitors but can be a very short time frame for evaluating safety, “based on the occurrence of adverse events,” according to the study description at clinicaltrials.gov.

The primary endpoint is change on the Assessment of SpondyloArthritis international Society (ASAS) Health Index-Numerical Rating Score over the 1 year of follow-up.

There are 11 secondary endpoints, including:

• Percentage reaching major improvement in the Ankylosing Spondylitis Disease Activity Scale score (ASDAS).
• Percentage reaching 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at 1 year.
• Change in the ASAS-NSAID score over 1 year.
• Change in the Work Productivity and Activity Impairment questionnaire.

The study is being conducted at 18 centers in Belgium, France, and the Netherlands and is sponsored by the Association de Recherche Clinique en Rhumatologie.
 

AScalate: Treat-to-target in axial spondyloarthritis

The Novartis-sponsored AScalate study seeks to enroll 300 patients with active disease despite NSAID therapy. The 36-week, randomized, parallel-group, open-label, multicenter trial will be conducted at seven sites in Germany.

The study will randomize patients to either of two arms: An active group will receive T2T therapy with secukinumab as a first-line biologic in escalating doses of 150-300 mg, determined by patient response until the T2T goal had been reached. Patients who don’t respond to secukinumab will be switched to an adalimumab biosimilar. The comparator group will receive standard-of-care therapy up to the maximum recommended dose at the discretion of the investigator.

The primary endpoint is the percentage of patients in each group who meet ASAS 40 response criteria by 24 weeks.

There are 11 secondary endpoints, including:

• Percentage achieving an ASAS40 response at 12 weeks.
• Percentage achieving ASAS20 and ASAS partial response at 12 and 24 weeks.
• Proportion of patients meeting the ASDAS definition of inactive disease, ASDAS clinically important and major improvement, and ASDAS low disease activity.
• Proportion of patients achieving 50% improvement of the initial BASDAI score.

Treat-to-target with secukinumab in axial spondyloarthritis (TRACE)

TRACE is a Novartis-sponsored phase 4 study examining reductions of inflammation seen on MRI of sacroiliac joints and spine at 16-24 weeks in patients who achieve ASDAS remission (score of less than 1.3) on 150 mg secukinumab by 16 weeks. The comparator group will be patients who are not in remission by week 16 and need a dose increase to 300 mg. The Danish trial seeks 88 participants with high disease activity and MRI signs of inflammation in the sacroiliac joints and/ or the spine.

After an initial four weekly doses of secukinumab 150 mg, patients will receive monthly secukinumab 150-mg doses out to week 16. Nonresponders at week 16 will escalate to 300 mg. If by 24 weeks these patients do not respond, they will be switched to a TNF inhibitor.

The primary outcome is the proportion of patients with a positive change in MRI-inflammation as measured by the sum of the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint and spine inflammation indices.

[email protected]

Three international clinical trials in Europe are examining the effectiveness of treat-to-target (T2T) therapeutic regimens in patients with axial spondyloarthritis (axSpA), including two that will be the first randomized trial evidence to support or refute the T2T strategy for patients ranging from those with nonradiographic disease to patients with ankylosing spondylitis.

T2T has proved before to work in patients with rheumatoid arthritis and psoriatic arthritis with evidence from the TICORA (Tight Control of Rheumatoid Arthritis) and TICOPA (Tight Control in Psoriatic Arthritis) trials.

Two T2T trials in axSpA are still in the recruiting phase, and one has completed enrollment, with no results available yet.
 

Tight control in spondyloarthritis (TICOSPA)

TICOSPA is a 1-year, ongoing, multinational, cluster-randomized, prospective cohort study that has enrolled 163 patients with a diagnosis of active axial spondyloarthritis to evaluate the potential benefit of a T2T strategy in which the rheumatologist will agree to monitor very closely – at least every 4 weeks – and treat patients in accordance with a predefined strategy. The T2T strategy is compared with usual care as given by the treating rheumatologist. Prior to the trial, patients were on nonoptimal NSAID treatment.

“Tight control” in this study refers to the time from treatment initiation to adequate assessment of efficacy and safety, which for efficacy should be at 2-4 weeks for NSAIDs and 12-16 weeks for tumor necrosis factor inhibitors but can be a very short time frame for evaluating safety, “based on the occurrence of adverse events,” according to the study description at clinicaltrials.gov.

The primary endpoint is change on the Assessment of SpondyloArthritis international Society (ASAS) Health Index-Numerical Rating Score over the 1 year of follow-up.

There are 11 secondary endpoints, including:

• Percentage reaching major improvement in the Ankylosing Spondylitis Disease Activity Scale score (ASDAS).
• Percentage reaching 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at 1 year.
• Change in the ASAS-NSAID score over 1 year.
• Change in the Work Productivity and Activity Impairment questionnaire.

The study is being conducted at 18 centers in Belgium, France, and the Netherlands and is sponsored by the Association de Recherche Clinique en Rhumatologie.
 

AScalate: Treat-to-target in axial spondyloarthritis

The Novartis-sponsored AScalate study seeks to enroll 300 patients with active disease despite NSAID therapy. The 36-week, randomized, parallel-group, open-label, multicenter trial will be conducted at seven sites in Germany.

The study will randomize patients to either of two arms: An active group will receive T2T therapy with secukinumab as a first-line biologic in escalating doses of 150-300 mg, determined by patient response until the T2T goal had been reached. Patients who don’t respond to secukinumab will be switched to an adalimumab biosimilar. The comparator group will receive standard-of-care therapy up to the maximum recommended dose at the discretion of the investigator.

The primary endpoint is the percentage of patients in each group who meet ASAS 40 response criteria by 24 weeks.

There are 11 secondary endpoints, including:

• Percentage achieving an ASAS40 response at 12 weeks.
• Percentage achieving ASAS20 and ASAS partial response at 12 and 24 weeks.
• Proportion of patients meeting the ASDAS definition of inactive disease, ASDAS clinically important and major improvement, and ASDAS low disease activity.
• Proportion of patients achieving 50% improvement of the initial BASDAI score.

Treat-to-target with secukinumab in axial spondyloarthritis (TRACE)

TRACE is a Novartis-sponsored phase 4 study examining reductions of inflammation seen on MRI of sacroiliac joints and spine at 16-24 weeks in patients who achieve ASDAS remission (score of less than 1.3) on 150 mg secukinumab by 16 weeks. The comparator group will be patients who are not in remission by week 16 and need a dose increase to 300 mg. The Danish trial seeks 88 participants with high disease activity and MRI signs of inflammation in the sacroiliac joints and/ or the spine.

After an initial four weekly doses of secukinumab 150 mg, patients will receive monthly secukinumab 150-mg doses out to week 16. Nonresponders at week 16 will escalate to 300 mg. If by 24 weeks these patients do not respond, they will be switched to a TNF inhibitor.

The primary outcome is the proportion of patients with a positive change in MRI-inflammation as measured by the sum of the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint and spine inflammation indices.

[email protected]

Three international clinical trials in Europe are examining the effectiveness of treat-to-target (T2T) therapeutic regimens in patients with axial spondyloarthritis (axSpA), including two that will be the first randomized trial evidence to support or refute the T2T strategy for patients ranging from those with nonradiographic disease to patients with ankylosing spondylitis.

T2T has proved before to work in patients with rheumatoid arthritis and psoriatic arthritis with evidence from the TICORA (Tight Control of Rheumatoid Arthritis) and TICOPA (Tight Control in Psoriatic Arthritis) trials.

Two T2T trials in axSpA are still in the recruiting phase, and one has completed enrollment, with no results available yet.
 

Tight control in spondyloarthritis (TICOSPA)

TICOSPA is a 1-year, ongoing, multinational, cluster-randomized, prospective cohort study that has enrolled 163 patients with a diagnosis of active axial spondyloarthritis to evaluate the potential benefit of a T2T strategy in which the rheumatologist will agree to monitor very closely – at least every 4 weeks – and treat patients in accordance with a predefined strategy. The T2T strategy is compared with usual care as given by the treating rheumatologist. Prior to the trial, patients were on nonoptimal NSAID treatment.

“Tight control” in this study refers to the time from treatment initiation to adequate assessment of efficacy and safety, which for efficacy should be at 2-4 weeks for NSAIDs and 12-16 weeks for tumor necrosis factor inhibitors but can be a very short time frame for evaluating safety, “based on the occurrence of adverse events,” according to the study description at clinicaltrials.gov.

The primary endpoint is change on the Assessment of SpondyloArthritis international Society (ASAS) Health Index-Numerical Rating Score over the 1 year of follow-up.

There are 11 secondary endpoints, including:

• Percentage reaching major improvement in the Ankylosing Spondylitis Disease Activity Scale score (ASDAS).
• Percentage reaching 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at 1 year.
• Change in the ASAS-NSAID score over 1 year.
• Change in the Work Productivity and Activity Impairment questionnaire.

The study is being conducted at 18 centers in Belgium, France, and the Netherlands and is sponsored by the Association de Recherche Clinique en Rhumatologie.
 

AScalate: Treat-to-target in axial spondyloarthritis

The Novartis-sponsored AScalate study seeks to enroll 300 patients with active disease despite NSAID therapy. The 36-week, randomized, parallel-group, open-label, multicenter trial will be conducted at seven sites in Germany.

The study will randomize patients to either of two arms: An active group will receive T2T therapy with secukinumab as a first-line biologic in escalating doses of 150-300 mg, determined by patient response until the T2T goal had been reached. Patients who don’t respond to secukinumab will be switched to an adalimumab biosimilar. The comparator group will receive standard-of-care therapy up to the maximum recommended dose at the discretion of the investigator.

The primary endpoint is the percentage of patients in each group who meet ASAS 40 response criteria by 24 weeks.

There are 11 secondary endpoints, including:

• Percentage achieving an ASAS40 response at 12 weeks.
• Percentage achieving ASAS20 and ASAS partial response at 12 and 24 weeks.
• Proportion of patients meeting the ASDAS definition of inactive disease, ASDAS clinically important and major improvement, and ASDAS low disease activity.
• Proportion of patients achieving 50% improvement of the initial BASDAI score.

Treat-to-target with secukinumab in axial spondyloarthritis (TRACE)

TRACE is a Novartis-sponsored phase 4 study examining reductions of inflammation seen on MRI of sacroiliac joints and spine at 16-24 weeks in patients who achieve ASDAS remission (score of less than 1.3) on 150 mg secukinumab by 16 weeks. The comparator group will be patients who are not in remission by week 16 and need a dose increase to 300 mg. The Danish trial seeks 88 participants with high disease activity and MRI signs of inflammation in the sacroiliac joints and/ or the spine.

After an initial four weekly doses of secukinumab 150 mg, patients will receive monthly secukinumab 150-mg doses out to week 16. Nonresponders at week 16 will escalate to 300 mg. If by 24 weeks these patients do not respond, they will be switched to a TNF inhibitor.

The primary outcome is the proportion of patients with a positive change in MRI-inflammation as measured by the sum of the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint and spine inflammation indices.

[email protected]

A new study has found that ankylosing spondylitis (AS) and axial psoriatic arthritis (axPsA) may be different diseases with overlapping features rather than entities on the spectrum of the same disease, building on previous research by analyzing AS patients with and without psoriasis and including a longitudinal analysis.

lolostock/Thinkstock

“Our study suggests that axial PsA and AS with psoriasis seem to be two different diseases with different genetics, demographics, and disease expression,” wrote Joy Feld, MD, of the University of Toronto and coauthors. Their findings were published in Rheumatology.

To investigate the similarities and differences between axPsA and AS patients, the researchers compared two adult cohorts recruited from Toronto clinics. The first was made up of AS patients and divided into two groups: with psoriasis (n = 91) and without psoriasis (n = 675). The second was made up of PsA patients and divided into two groups: axPsA (n = 477) and peripheral PsA (n = 826).

In comparing AS patients with and without psoriasis to axPsA patients, AS patients had a younger age at diagnosis (28.7 years and 30.4 years vs. 35.6 years; P less than .001), were more often male (76% and 72% vs. 64%; P less than .001), and were more likely to be HLA-B27 positive (82% and 75% vs. 19%; P less than .001).

At baseline, AS patients had more back pain (90% and 92% vs. 21%; P less than .001) and worse back metrology (Bath Ankylosing Spondylitis Metrology Index [BASMI] of 3.1 and 2.3 vs. 1.9; P less than .001).

The mean follow-up periods in the axial and peripheral PsA groups were 12.6 and 6.7 years, respectively, whereas in the AS groups with and without psoriasis the periods were 5.4 and 3.5 years. Over time and after longitudinal analysis, axPsA patients had more tender and swollen joints than AS patients with and without psoriasis (5.2 vs. 1.5 and 0.9; P less than .001) while AS patients with and without psoriasis had a higher BASMI (2.9 and 2.2 vs. 1.8; P less than .001) and worse axial disease activity scores (4.1 and 3.9 vs. 3.5; P = .02) as measured by the Bath Ankylosing Spondylitis Disease Activity Index.

After univariate analysis, AS with psoriasis was found to be more associated with HLA-B27 (odds ratio, 16.37; 95% confidence interval, 8.89-30.13; P less than .0001), a higher adjusted mean BASMI (OR, 1.41; 95% CI, 1.21-1.63; P less than .0001), worse sacroiliitis (OR, 7.58; 95% CI, 3.68-15.59; P less than .0001), and greater use of biologics (OR, 1.25; 95% CI, 0.77-1; P = .37), compared with axPsA. A multivariate analysis produced similar findings, including the lack of association between AS and active arthritis (OR, 0.75; 95% CI, 0.64-0.86; P less than .0001).

The authors acknowledged their study’s limitations, including the fact that symptoms often dictate which of the two clinics patients will be referred to, which can ultimately define the diagnosis. “Patients with significant back symptoms are more likely to be referred to the AS clinic,” they wrote, “while patients with more prominent peripheral symptoms are more likely to be referred to the PsA clinic.” Patients with AS in the study were also required to have back pain or limitations in spinal range of motion, while PsA patients were accepted even if they were asymptomatic.

Finally, they noted that some milder cases of the two diseases may have been missed in the cohort recruiting process, although they added that mild cases were, in fact, “present in the cohort, which might improve the generalizability of this study to primary rheumatology clinics.”

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation, but this study received no specific funding to carry out the research. Dr. Feld reported being supported by a grant from Novartis. The authors reported no conflicts of interest.

SOURCE: Feld J et al. Rheumatology. 2019 Oct 8. doi: 10.1093/rheumatology/kez457.

A new study has found that ankylosing spondylitis (AS) and axial psoriatic arthritis (axPsA) may be different diseases with overlapping features rather than entities on the spectrum of the same disease, building on previous research by analyzing AS patients with and without psoriasis and including a longitudinal analysis.

lolostock/Thinkstock

“Our study suggests that axial PsA and AS with psoriasis seem to be two different diseases with different genetics, demographics, and disease expression,” wrote Joy Feld, MD, of the University of Toronto and coauthors. Their findings were published in Rheumatology.

To investigate the similarities and differences between axPsA and AS patients, the researchers compared two adult cohorts recruited from Toronto clinics. The first was made up of AS patients and divided into two groups: with psoriasis (n = 91) and without psoriasis (n = 675). The second was made up of PsA patients and divided into two groups: axPsA (n = 477) and peripheral PsA (n = 826).

In comparing AS patients with and without psoriasis to axPsA patients, AS patients had a younger age at diagnosis (28.7 years and 30.4 years vs. 35.6 years; P less than .001), were more often male (76% and 72% vs. 64%; P less than .001), and were more likely to be HLA-B27 positive (82% and 75% vs. 19%; P less than .001).

At baseline, AS patients had more back pain (90% and 92% vs. 21%; P less than .001) and worse back metrology (Bath Ankylosing Spondylitis Metrology Index [BASMI] of 3.1 and 2.3 vs. 1.9; P less than .001).

The mean follow-up periods in the axial and peripheral PsA groups were 12.6 and 6.7 years, respectively, whereas in the AS groups with and without psoriasis the periods were 5.4 and 3.5 years. Over time and after longitudinal analysis, axPsA patients had more tender and swollen joints than AS patients with and without psoriasis (5.2 vs. 1.5 and 0.9; P less than .001) while AS patients with and without psoriasis had a higher BASMI (2.9 and 2.2 vs. 1.8; P less than .001) and worse axial disease activity scores (4.1 and 3.9 vs. 3.5; P = .02) as measured by the Bath Ankylosing Spondylitis Disease Activity Index.

After univariate analysis, AS with psoriasis was found to be more associated with HLA-B27 (odds ratio, 16.37; 95% confidence interval, 8.89-30.13; P less than .0001), a higher adjusted mean BASMI (OR, 1.41; 95% CI, 1.21-1.63; P less than .0001), worse sacroiliitis (OR, 7.58; 95% CI, 3.68-15.59; P less than .0001), and greater use of biologics (OR, 1.25; 95% CI, 0.77-1; P = .37), compared with axPsA. A multivariate analysis produced similar findings, including the lack of association between AS and active arthritis (OR, 0.75; 95% CI, 0.64-0.86; P less than .0001).

The authors acknowledged their study’s limitations, including the fact that symptoms often dictate which of the two clinics patients will be referred to, which can ultimately define the diagnosis. “Patients with significant back symptoms are more likely to be referred to the AS clinic,” they wrote, “while patients with more prominent peripheral symptoms are more likely to be referred to the PsA clinic.” Patients with AS in the study were also required to have back pain or limitations in spinal range of motion, while PsA patients were accepted even if they were asymptomatic.

Finally, they noted that some milder cases of the two diseases may have been missed in the cohort recruiting process, although they added that mild cases were, in fact, “present in the cohort, which might improve the generalizability of this study to primary rheumatology clinics.”

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation, but this study received no specific funding to carry out the research. Dr. Feld reported being supported by a grant from Novartis. The authors reported no conflicts of interest.

SOURCE: Feld J et al. Rheumatology. 2019 Oct 8. doi: 10.1093/rheumatology/kez457.

A new study has found that ankylosing spondylitis (AS) and axial psoriatic arthritis (axPsA) may be different diseases with overlapping features rather than entities on the spectrum of the same disease, building on previous research by analyzing AS patients with and without psoriasis and including a longitudinal analysis.

lolostock/Thinkstock

“Our study suggests that axial PsA and AS with psoriasis seem to be two different diseases with different genetics, demographics, and disease expression,” wrote Joy Feld, MD, of the University of Toronto and coauthors. Their findings were published in Rheumatology.

To investigate the similarities and differences between axPsA and AS patients, the researchers compared two adult cohorts recruited from Toronto clinics. The first was made up of AS patients and divided into two groups: with psoriasis (n = 91) and without psoriasis (n = 675). The second was made up of PsA patients and divided into two groups: axPsA (n = 477) and peripheral PsA (n = 826).

In comparing AS patients with and without psoriasis to axPsA patients, AS patients had a younger age at diagnosis (28.7 years and 30.4 years vs. 35.6 years; P less than .001), were more often male (76% and 72% vs. 64%; P less than .001), and were more likely to be HLA-B27 positive (82% and 75% vs. 19%; P less than .001).

At baseline, AS patients had more back pain (90% and 92% vs. 21%; P less than .001) and worse back metrology (Bath Ankylosing Spondylitis Metrology Index [BASMI] of 3.1 and 2.3 vs. 1.9; P less than .001).

The mean follow-up periods in the axial and peripheral PsA groups were 12.6 and 6.7 years, respectively, whereas in the AS groups with and without psoriasis the periods were 5.4 and 3.5 years. Over time and after longitudinal analysis, axPsA patients had more tender and swollen joints than AS patients with and without psoriasis (5.2 vs. 1.5 and 0.9; P less than .001) while AS patients with and without psoriasis had a higher BASMI (2.9 and 2.2 vs. 1.8; P less than .001) and worse axial disease activity scores (4.1 and 3.9 vs. 3.5; P = .02) as measured by the Bath Ankylosing Spondylitis Disease Activity Index.

After univariate analysis, AS with psoriasis was found to be more associated with HLA-B27 (odds ratio, 16.37; 95% confidence interval, 8.89-30.13; P less than .0001), a higher adjusted mean BASMI (OR, 1.41; 95% CI, 1.21-1.63; P less than .0001), worse sacroiliitis (OR, 7.58; 95% CI, 3.68-15.59; P less than .0001), and greater use of biologics (OR, 1.25; 95% CI, 0.77-1; P = .37), compared with axPsA. A multivariate analysis produced similar findings, including the lack of association between AS and active arthritis (OR, 0.75; 95% CI, 0.64-0.86; P less than .0001).

The authors acknowledged their study’s limitations, including the fact that symptoms often dictate which of the two clinics patients will be referred to, which can ultimately define the diagnosis. “Patients with significant back symptoms are more likely to be referred to the AS clinic,” they wrote, “while patients with more prominent peripheral symptoms are more likely to be referred to the PsA clinic.” Patients with AS in the study were also required to have back pain or limitations in spinal range of motion, while PsA patients were accepted even if they were asymptomatic.

Finally, they noted that some milder cases of the two diseases may have been missed in the cohort recruiting process, although they added that mild cases were, in fact, “present in the cohort, which might improve the generalizability of this study to primary rheumatology clinics.”

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation, but this study received no specific funding to carry out the research. Dr. Feld reported being supported by a grant from Novartis. The authors reported no conflicts of interest.

SOURCE: Feld J et al. Rheumatology. 2019 Oct 8. doi: 10.1093/rheumatology/kez457.