Spondyloarthropathies

Interrupting biologic therapy before surgery led to flares in psoriasis and psoriatic arthritis and did not appear to prevent postoperative complications in a small, retrospective cohort study.

“Our findings are in keeping with most of the existing literature on this topic,” said Dr. Waseem Bakkour and his associates at the University of Manchester (England). “However, it is important to acknowledge the deficiencies of our data, in particular the small data set and retrospective study design with numerous complexities associated with interpreting it” (J. Eur. Acad. Dermatol. Venereol. 2015 Mar. 2 [doi:10.1111/jdv.12997]).

The British Association of Dermatologists and the British Society for Rheumatology recommend stopping biologics for at least four half-lives before surgery, but the guideline is based mostly on retrospective studies of rheumatoid arthritis and inflammatory bowel disease, the researchers said. For their study, they reviewed electronic health records from 42 patients with psoriasis and psoriatic arthritis who underwent 77 major and minor surgical procedures during a 6-year period. Discontinuing biologic therapy before surgery was linked to a significant risk of flare of psoriasis or psoriatic arthritis (40% with stoppage vs. 8.7% with continuation; P = .003). For three-quarters of procedures, patients continued biologic therapy (usually etanercept, but also adalimumab and infliximab), with no apparent effect on rates of postoperative infections or delayed wound healing. About 48% of procedures required general anesthesia, and most of the rest were skin surgeries.

The findings contradict those from a larger retrospective study (Arthritis Care Res. 2006;55:333-7) that linked biologic therapy before orthopedic surgery to a fourfold rise in the odds of postoperative infections, the investigators noted. “Whilst the current evidence, not surprisingly, suggests a link between stopping treatment and disease flare, it remains equivocal regarding the question of whether continuing biologic therapy perioperatively increases the risk of postsurgical complications,” they wrote.

The authors reported no funding sources. They disclosed financial and advisory relationships with many companies that manufacture biologic therapies.

Interrupting biologic therapy before surgery led to flares in psoriasis and psoriatic arthritis and did not appear to prevent postoperative complications in a small, retrospective cohort study.

“Our findings are in keeping with most of the existing literature on this topic,” said Dr. Waseem Bakkour and his associates at the University of Manchester (England). “However, it is important to acknowledge the deficiencies of our data, in particular the small data set and retrospective study design with numerous complexities associated with interpreting it” (J. Eur. Acad. Dermatol. Venereol. 2015 Mar. 2 [doi:10.1111/jdv.12997]).

The British Association of Dermatologists and the British Society for Rheumatology recommend stopping biologics for at least four half-lives before surgery, but the guideline is based mostly on retrospective studies of rheumatoid arthritis and inflammatory bowel disease, the researchers said. For their study, they reviewed electronic health records from 42 patients with psoriasis and psoriatic arthritis who underwent 77 major and minor surgical procedures during a 6-year period. Discontinuing biologic therapy before surgery was linked to a significant risk of flare of psoriasis or psoriatic arthritis (40% with stoppage vs. 8.7% with continuation; P = .003). For three-quarters of procedures, patients continued biologic therapy (usually etanercept, but also adalimumab and infliximab), with no apparent effect on rates of postoperative infections or delayed wound healing. About 48% of procedures required general anesthesia, and most of the rest were skin surgeries.

The findings contradict those from a larger retrospective study (Arthritis Care Res. 2006;55:333-7) that linked biologic therapy before orthopedic surgery to a fourfold rise in the odds of postoperative infections, the investigators noted. “Whilst the current evidence, not surprisingly, suggests a link between stopping treatment and disease flare, it remains equivocal regarding the question of whether continuing biologic therapy perioperatively increases the risk of postsurgical complications,” they wrote.

The authors reported no funding sources. They disclosed financial and advisory relationships with many companies that manufacture biologic therapies.

Interrupting biologic therapy before surgery led to flares in psoriasis and psoriatic arthritis and did not appear to prevent postoperative complications in a small, retrospective cohort study.

“Our findings are in keeping with most of the existing literature on this topic,” said Dr. Waseem Bakkour and his associates at the University of Manchester (England). “However, it is important to acknowledge the deficiencies of our data, in particular the small data set and retrospective study design with numerous complexities associated with interpreting it” (J. Eur. Acad. Dermatol. Venereol. 2015 Mar. 2 [doi:10.1111/jdv.12997]).

The British Association of Dermatologists and the British Society for Rheumatology recommend stopping biologics for at least four half-lives before surgery, but the guideline is based mostly on retrospective studies of rheumatoid arthritis and inflammatory bowel disease, the researchers said. For their study, they reviewed electronic health records from 42 patients with psoriasis and psoriatic arthritis who underwent 77 major and minor surgical procedures during a 6-year period. Discontinuing biologic therapy before surgery was linked to a significant risk of flare of psoriasis or psoriatic arthritis (40% with stoppage vs. 8.7% with continuation; P = .003). For three-quarters of procedures, patients continued biologic therapy (usually etanercept, but also adalimumab and infliximab), with no apparent effect on rates of postoperative infections or delayed wound healing. About 48% of procedures required general anesthesia, and most of the rest were skin surgeries.

The findings contradict those from a larger retrospective study (Arthritis Care Res. 2006;55:333-7) that linked biologic therapy before orthopedic surgery to a fourfold rise in the odds of postoperative infections, the investigators noted. “Whilst the current evidence, not surprisingly, suggests a link between stopping treatment and disease flare, it remains equivocal regarding the question of whether continuing biologic therapy perioperatively increases the risk of postsurgical complications,” they wrote.

The authors reported no funding sources. They disclosed financial and advisory relationships with many companies that manufacture biologic therapies.

A monoclonal antibody targeting an interleukin-23 subunit has shown a significant reduction in psoriasis area and disease severity in 77 psoriasis patients, according to data from a randomized, placebo-controlled phase I trial.

Three doses of intravenous tildrakizumab (0.05–10 mg/kg1) – given 1-2 months apart – were associated with 50%-80% reductions in mean placebo-corrected psoriasis area and severity index (PASI) scores at 112 days after commencing treatment, and was well tolerated with minor adverse events.

Researchers observed 50% reductions in PASI score 308 days after the last administered dose, and all subjects given 3 or 10 mg/kg achieved a 75% reduction in PASI score by day 196, according to a paper published online March 9 in Nature (doi: 10.1038/nature14175).

“Further development of tildrakizumab is warranted based on these results to determine whether selective targeting of IL-23 can provide similar or better efficacy while reducing safety concerns that are associated with other biologic agents currently approved for the treatment of psoriasis,” wrote Dr. Tamara Kopp, from the Juvenis Medical Center, Vienna, and coauthors.

The study was funded by tildrakizumab-developer Merck & Co. Inc, and several authors were employees of Merck & Co. Inc.

A monoclonal antibody targeting an interleukin-23 subunit has shown a significant reduction in psoriasis area and disease severity in 77 psoriasis patients, according to data from a randomized, placebo-controlled phase I trial.

Three doses of intravenous tildrakizumab (0.05–10 mg/kg1) – given 1-2 months apart – were associated with 50%-80% reductions in mean placebo-corrected psoriasis area and severity index (PASI) scores at 112 days after commencing treatment, and was well tolerated with minor adverse events.

Researchers observed 50% reductions in PASI score 308 days after the last administered dose, and all subjects given 3 or 10 mg/kg achieved a 75% reduction in PASI score by day 196, according to a paper published online March 9 in Nature (doi: 10.1038/nature14175).

“Further development of tildrakizumab is warranted based on these results to determine whether selective targeting of IL-23 can provide similar or better efficacy while reducing safety concerns that are associated with other biologic agents currently approved for the treatment of psoriasis,” wrote Dr. Tamara Kopp, from the Juvenis Medical Center, Vienna, and coauthors.

The study was funded by tildrakizumab-developer Merck & Co. Inc, and several authors were employees of Merck & Co. Inc.

A monoclonal antibody targeting an interleukin-23 subunit has shown a significant reduction in psoriasis area and disease severity in 77 psoriasis patients, according to data from a randomized, placebo-controlled phase I trial.

Three doses of intravenous tildrakizumab (0.05–10 mg/kg1) – given 1-2 months apart – were associated with 50%-80% reductions in mean placebo-corrected psoriasis area and severity index (PASI) scores at 112 days after commencing treatment, and was well tolerated with minor adverse events.

Researchers observed 50% reductions in PASI score 308 days after the last administered dose, and all subjects given 3 or 10 mg/kg achieved a 75% reduction in PASI score by day 196, according to a paper published online March 9 in Nature (doi: 10.1038/nature14175).

“Further development of tildrakizumab is warranted based on these results to determine whether selective targeting of IL-23 can provide similar or better efficacy while reducing safety concerns that are associated with other biologic agents currently approved for the treatment of psoriasis,” wrote Dr. Tamara Kopp, from the Juvenis Medical Center, Vienna, and coauthors.

The study was funded by tildrakizumab-developer Merck & Co. Inc, and several authors were employees of Merck & Co. Inc.

SNOWMASS, COLO. – Ankylosing spondylitis, far and away, is the most common systemic disease in North America associated with uveitis, Dr. James T. Rosenbaum said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

The uveitis associated with ankylosing spondylitis and other HLA-B27-positive axial spondyloarthropathies is highly distinctive: It’s an anterior uveitis, meaning it occurs in front of the lens. It is sudden in onset, unilateral, often recurs in the opposite eye, and it resolves completely between attacks within several months. Also, it is associated with reduced intraocular pressure, according to Dr. Rosenbaum, professor of inflammatory diseases and chief of the division of arthritis and rheumatic diseases at Oregon Health & Science University and chief of ophthalmology at the Devers Eye Institute in Portland, Ore.

The differential diagnosis for a red eye is extensive. It includes conjunctivitis, scleritis, episcleritis, keratitis, and acute closed angle glaucoma, as well as anterior uveitis. But the only cause of a red eye that results in a constricted pupil is a sudden-onset acute anterior uveitis, he noted.

A patient with acute anterior uveitis has a 50% likelihood of being HLA-B27-positive. And a B27-positive patient with acute anterior uveitis and inflammatory back pain has nearly a 90% chance of having a spondyloarthropathy. Roughly half of these individuals meet diagnostic criteria for ankylosing spondylitis, and another 40% fulfill the Assessment of Spondyloarthritis International Society definition of spondyloarthritis, which doesn’t require definite evidence of inflammation of the sacroiliac joints on plain x-rays. An analysis of National Health and Nutrition Examination Survey data showed that 1% of U.S. adults have axial spondyloarthritis (Arthritis Care Res. 2012;64:905-10).

Yet in Dr. Rosenbaum’s experience, two-thirds of patients who present with HLA-B27-positive, unilateral, sudden-onset acute anterior uveitis have no idea that their inflammatory low back pain is a manifestation of ankylosing spondylitis or axial spondyloarthritis.

“Back pain is so endemic in our society that it’s rarely realized that the chronic back inflammation is related to the eye disease,” he observed.

Dr. Rosenbaum said that for most nonophthalmologists, uveitis flies under the radar.

“Most people don’t know what it is, but uveitis actually accounts for about 10% of all cases of blindness. And it’s a disease that often occurs in the prime of life, unlike macular degeneration or blindness due to diabetes,” he continued.

His uveitis treatment ladder starts with topical corticosteroids, which are often quite effective for anterior uveitis. Second-line therapy consists of periocular or intravitreal steroid injections, “just like you’d inject a shoulder or knee.” Oral corticosteroids are effective, but their long-term use is problematic, so Dr. Rosenbaum will quickly switch to an antimetabolite, with methotrexate his top choice.

“I would never use a TNF inhibitor to treat spondyloarthropathy-associated acute anterior uveitis per se, because this type of uveitis is typically short lived. As a practical matter, by the time I got approval from the third-party payer the uveitis would be gone. But if a patient is having recurrent severe episodes of uveitis, a TNF inhibitor will reduce the intensity and frequency of those flares. So will sulfasalazine. Methotrexate will, too, but it doesn’t affect the spondyloarthropathy,” he said.

Dr. Rosenbaum reported receiving consulting fees from a dozen pharmaceutical companies and research grants from AbbVie, Eyegate, Genentech, and Psivida.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Ankylosing spondylitis, far and away, is the most common systemic disease in North America associated with uveitis, Dr. James T. Rosenbaum said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

The uveitis associated with ankylosing spondylitis and other HLA-B27-positive axial spondyloarthropathies is highly distinctive: It’s an anterior uveitis, meaning it occurs in front of the lens. It is sudden in onset, unilateral, often recurs in the opposite eye, and it resolves completely between attacks within several months. Also, it is associated with reduced intraocular pressure, according to Dr. Rosenbaum, professor of inflammatory diseases and chief of the division of arthritis and rheumatic diseases at Oregon Health & Science University and chief of ophthalmology at the Devers Eye Institute in Portland, Ore.

The differential diagnosis for a red eye is extensive. It includes conjunctivitis, scleritis, episcleritis, keratitis, and acute closed angle glaucoma, as well as anterior uveitis. But the only cause of a red eye that results in a constricted pupil is a sudden-onset acute anterior uveitis, he noted.

A patient with acute anterior uveitis has a 50% likelihood of being HLA-B27-positive. And a B27-positive patient with acute anterior uveitis and inflammatory back pain has nearly a 90% chance of having a spondyloarthropathy. Roughly half of these individuals meet diagnostic criteria for ankylosing spondylitis, and another 40% fulfill the Assessment of Spondyloarthritis International Society definition of spondyloarthritis, which doesn’t require definite evidence of inflammation of the sacroiliac joints on plain x-rays. An analysis of National Health and Nutrition Examination Survey data showed that 1% of U.S. adults have axial spondyloarthritis (Arthritis Care Res. 2012;64:905-10).

Yet in Dr. Rosenbaum’s experience, two-thirds of patients who present with HLA-B27-positive, unilateral, sudden-onset acute anterior uveitis have no idea that their inflammatory low back pain is a manifestation of ankylosing spondylitis or axial spondyloarthritis.

“Back pain is so endemic in our society that it’s rarely realized that the chronic back inflammation is related to the eye disease,” he observed.

Dr. Rosenbaum said that for most nonophthalmologists, uveitis flies under the radar.

“Most people don’t know what it is, but uveitis actually accounts for about 10% of all cases of blindness. And it’s a disease that often occurs in the prime of life, unlike macular degeneration or blindness due to diabetes,” he continued.

His uveitis treatment ladder starts with topical corticosteroids, which are often quite effective for anterior uveitis. Second-line therapy consists of periocular or intravitreal steroid injections, “just like you’d inject a shoulder or knee.” Oral corticosteroids are effective, but their long-term use is problematic, so Dr. Rosenbaum will quickly switch to an antimetabolite, with methotrexate his top choice.

“I would never use a TNF inhibitor to treat spondyloarthropathy-associated acute anterior uveitis per se, because this type of uveitis is typically short lived. As a practical matter, by the time I got approval from the third-party payer the uveitis would be gone. But if a patient is having recurrent severe episodes of uveitis, a TNF inhibitor will reduce the intensity and frequency of those flares. So will sulfasalazine. Methotrexate will, too, but it doesn’t affect the spondyloarthropathy,” he said.

Dr. Rosenbaum reported receiving consulting fees from a dozen pharmaceutical companies and research grants from AbbVie, Eyegate, Genentech, and Psivida.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Ankylosing spondylitis, far and away, is the most common systemic disease in North America associated with uveitis, Dr. James T. Rosenbaum said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

The uveitis associated with ankylosing spondylitis and other HLA-B27-positive axial spondyloarthropathies is highly distinctive: It’s an anterior uveitis, meaning it occurs in front of the lens. It is sudden in onset, unilateral, often recurs in the opposite eye, and it resolves completely between attacks within several months. Also, it is associated with reduced intraocular pressure, according to Dr. Rosenbaum, professor of inflammatory diseases and chief of the division of arthritis and rheumatic diseases at Oregon Health & Science University and chief of ophthalmology at the Devers Eye Institute in Portland, Ore.

The differential diagnosis for a red eye is extensive. It includes conjunctivitis, scleritis, episcleritis, keratitis, and acute closed angle glaucoma, as well as anterior uveitis. But the only cause of a red eye that results in a constricted pupil is a sudden-onset acute anterior uveitis, he noted.

A patient with acute anterior uveitis has a 50% likelihood of being HLA-B27-positive. And a B27-positive patient with acute anterior uveitis and inflammatory back pain has nearly a 90% chance of having a spondyloarthropathy. Roughly half of these individuals meet diagnostic criteria for ankylosing spondylitis, and another 40% fulfill the Assessment of Spondyloarthritis International Society definition of spondyloarthritis, which doesn’t require definite evidence of inflammation of the sacroiliac joints on plain x-rays. An analysis of National Health and Nutrition Examination Survey data showed that 1% of U.S. adults have axial spondyloarthritis (Arthritis Care Res. 2012;64:905-10).

Yet in Dr. Rosenbaum’s experience, two-thirds of patients who present with HLA-B27-positive, unilateral, sudden-onset acute anterior uveitis have no idea that their inflammatory low back pain is a manifestation of ankylosing spondylitis or axial spondyloarthritis.

“Back pain is so endemic in our society that it’s rarely realized that the chronic back inflammation is related to the eye disease,” he observed.

Dr. Rosenbaum said that for most nonophthalmologists, uveitis flies under the radar.

“Most people don’t know what it is, but uveitis actually accounts for about 10% of all cases of blindness. And it’s a disease that often occurs in the prime of life, unlike macular degeneration or blindness due to diabetes,” he continued.

His uveitis treatment ladder starts with topical corticosteroids, which are often quite effective for anterior uveitis. Second-line therapy consists of periocular or intravitreal steroid injections, “just like you’d inject a shoulder or knee.” Oral corticosteroids are effective, but their long-term use is problematic, so Dr. Rosenbaum will quickly switch to an antimetabolite, with methotrexate his top choice.

“I would never use a TNF inhibitor to treat spondyloarthropathy-associated acute anterior uveitis per se, because this type of uveitis is typically short lived. As a practical matter, by the time I got approval from the third-party payer the uveitis would be gone. But if a patient is having recurrent severe episodes of uveitis, a TNF inhibitor will reduce the intensity and frequency of those flares. So will sulfasalazine. Methotrexate will, too, but it doesn’t affect the spondyloarthropathy,” he said.

Dr. Rosenbaum reported receiving consulting fees from a dozen pharmaceutical companies and research grants from AbbVie, Eyegate, Genentech, and Psivida.

bjancin@frontlinemedcom.com

Infliximab caused liver injury in 8.3% of treated patients in a prospective study, exceeding rates for other tumor necrosis factor-alpha antagonists, investigators reported online in Clinical Gastroenterology and Hepatology.

The findings show that “liver injury associated with the use of TNF-alpha antagonists is more common than previously reported, occurring in 1 in 120 of those exposed to infliximab,” said Dr. Einar S. Björnsson at the University of Iceland in Reykjavik and his associates. Furthermore, neither anti-TNF treatment dose nor baseline antinuclear acid antibody (ANA) status predicted which patients would develop drug-induced liver injury (DILI), the researchers said.

Since emerging in the 1990s, anti-TNF agents have dramatically altered the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Although they are known to cause liver damage in some patients, data on the topic mainly come from single case reports, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi: http://dx.doi.org/10.1016/j.cgh.2014.07.062]) To better understand the association, the researchers prospectively studied patients who received anti-TNF agents between 2009 and 2013 at the University Hospital in Iceland. They defined liver injury as aspartate aminotransferase or alanine aminotransferase (ALT) levels that were at least triple the normal upper limit, or alkaline phosphatase levels of at least double the upper limit.

A total of 1,776 patients were treated with anti-TNF agents during the 5-year study period, the researchers reported. In all, 11 developed drug-induced liver injury (DILI), of which nine cases were caused by infliximab, they said. Liver injury developed in 8.3% of patients treated with infliximab, compared with only 3.7% of those who received adalimumab and 2.3% of those given etanercept, they added. In a past analysis, the researchers calculated that one in every 148 patients would develop DILI during 2 years of treatment with infliximab (Gastroenterology 2014;144:1419-25). Patients who developed DILI on one anti-TNF agent were able to switch therapies without DILI recurring, the investigators said. Seven patients were switched from infliximab to adalimumab, etanercept, or both, and one was switched to infliximab after developing DILI on adalimumab, they added.

The researchers also compared the 11 cases to 22 randomized controls matched by age, sex, underlying condition, and treatment. Notably, among the 11 patients diagnosed with DILI, just 1 (9%) was receiving methotrexate at the time of diagnosis, compared with 59% of the controls (P = .009), they reported. “The reason for this is not clear,” they added. “Methotrexate has been shown to lead to a decrease in circulating autoantibodies in cutaneous lupus erythematosus, but the influence of methotrexate could not be confirmed during infliximab treatment.”

Five of the 11 patients with DILI had liver biopsies, of which three showed severe acute hepatitis, two indicated mild unspecified chronic hepatitis, and one showed pure canalicular cholestasis, the researchers reported. About half the patients needed steroids acutely, but “the vast majority” did not need long-term steroid treatment, they said. Exactly how anti-TNF agents cause liver injury remains unclear, they added. Future studies might evaluate whether these drugs trigger CD4 T cells to react against liver cells, as is the case in classic autoimmune hepatitis, they said.

The researchers reported no funding sources and declared having no conflicts of interest.

Infliximab caused liver injury in 8.3% of treated patients in a prospective study, exceeding rates for other tumor necrosis factor-alpha antagonists, investigators reported online in Clinical Gastroenterology and Hepatology.

The findings show that “liver injury associated with the use of TNF-alpha antagonists is more common than previously reported, occurring in 1 in 120 of those exposed to infliximab,” said Dr. Einar S. Björnsson at the University of Iceland in Reykjavik and his associates. Furthermore, neither anti-TNF treatment dose nor baseline antinuclear acid antibody (ANA) status predicted which patients would develop drug-induced liver injury (DILI), the researchers said.

Since emerging in the 1990s, anti-TNF agents have dramatically altered the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Although they are known to cause liver damage in some patients, data on the topic mainly come from single case reports, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi: http://dx.doi.org/10.1016/j.cgh.2014.07.062]) To better understand the association, the researchers prospectively studied patients who received anti-TNF agents between 2009 and 2013 at the University Hospital in Iceland. They defined liver injury as aspartate aminotransferase or alanine aminotransferase (ALT) levels that were at least triple the normal upper limit, or alkaline phosphatase levels of at least double the upper limit.

A total of 1,776 patients were treated with anti-TNF agents during the 5-year study period, the researchers reported. In all, 11 developed drug-induced liver injury (DILI), of which nine cases were caused by infliximab, they said. Liver injury developed in 8.3% of patients treated with infliximab, compared with only 3.7% of those who received adalimumab and 2.3% of those given etanercept, they added. In a past analysis, the researchers calculated that one in every 148 patients would develop DILI during 2 years of treatment with infliximab (Gastroenterology 2014;144:1419-25). Patients who developed DILI on one anti-TNF agent were able to switch therapies without DILI recurring, the investigators said. Seven patients were switched from infliximab to adalimumab, etanercept, or both, and one was switched to infliximab after developing DILI on adalimumab, they added.

The researchers also compared the 11 cases to 22 randomized controls matched by age, sex, underlying condition, and treatment. Notably, among the 11 patients diagnosed with DILI, just 1 (9%) was receiving methotrexate at the time of diagnosis, compared with 59% of the controls (P = .009), they reported. “The reason for this is not clear,” they added. “Methotrexate has been shown to lead to a decrease in circulating autoantibodies in cutaneous lupus erythematosus, but the influence of methotrexate could not be confirmed during infliximab treatment.”

Five of the 11 patients with DILI had liver biopsies, of which three showed severe acute hepatitis, two indicated mild unspecified chronic hepatitis, and one showed pure canalicular cholestasis, the researchers reported. About half the patients needed steroids acutely, but “the vast majority” did not need long-term steroid treatment, they said. Exactly how anti-TNF agents cause liver injury remains unclear, they added. Future studies might evaluate whether these drugs trigger CD4 T cells to react against liver cells, as is the case in classic autoimmune hepatitis, they said.

The researchers reported no funding sources and declared having no conflicts of interest.

Infliximab caused liver injury in 8.3% of treated patients in a prospective study, exceeding rates for other tumor necrosis factor-alpha antagonists, investigators reported online in Clinical Gastroenterology and Hepatology.

The findings show that “liver injury associated with the use of TNF-alpha antagonists is more common than previously reported, occurring in 1 in 120 of those exposed to infliximab,” said Dr. Einar S. Björnsson at the University of Iceland in Reykjavik and his associates. Furthermore, neither anti-TNF treatment dose nor baseline antinuclear acid antibody (ANA) status predicted which patients would develop drug-induced liver injury (DILI), the researchers said.

Since emerging in the 1990s, anti-TNF agents have dramatically altered the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Although they are known to cause liver damage in some patients, data on the topic mainly come from single case reports, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi: http://dx.doi.org/10.1016/j.cgh.2014.07.062]) To better understand the association, the researchers prospectively studied patients who received anti-TNF agents between 2009 and 2013 at the University Hospital in Iceland. They defined liver injury as aspartate aminotransferase or alanine aminotransferase (ALT) levels that were at least triple the normal upper limit, or alkaline phosphatase levels of at least double the upper limit.

A total of 1,776 patients were treated with anti-TNF agents during the 5-year study period, the researchers reported. In all, 11 developed drug-induced liver injury (DILI), of which nine cases were caused by infliximab, they said. Liver injury developed in 8.3% of patients treated with infliximab, compared with only 3.7% of those who received adalimumab and 2.3% of those given etanercept, they added. In a past analysis, the researchers calculated that one in every 148 patients would develop DILI during 2 years of treatment with infliximab (Gastroenterology 2014;144:1419-25). Patients who developed DILI on one anti-TNF agent were able to switch therapies without DILI recurring, the investigators said. Seven patients were switched from infliximab to adalimumab, etanercept, or both, and one was switched to infliximab after developing DILI on adalimumab, they added.

The researchers also compared the 11 cases to 22 randomized controls matched by age, sex, underlying condition, and treatment. Notably, among the 11 patients diagnosed with DILI, just 1 (9%) was receiving methotrexate at the time of diagnosis, compared with 59% of the controls (P = .009), they reported. “The reason for this is not clear,” they added. “Methotrexate has been shown to lead to a decrease in circulating autoantibodies in cutaneous lupus erythematosus, but the influence of methotrexate could not be confirmed during infliximab treatment.”

Five of the 11 patients with DILI had liver biopsies, of which three showed severe acute hepatitis, two indicated mild unspecified chronic hepatitis, and one showed pure canalicular cholestasis, the researchers reported. About half the patients needed steroids acutely, but “the vast majority” did not need long-term steroid treatment, they said. Exactly how anti-TNF agents cause liver injury remains unclear, they added. Future studies might evaluate whether these drugs trigger CD4 T cells to react against liver cells, as is the case in classic autoimmune hepatitis, they said.

The researchers reported no funding sources and declared having no conflicts of interest.

MIAMI BEACH – Two of the newest treatments available for psoriasis – apremilast and secukinumab – are true “game-changers,” according to Dr. David M. Pariser.

Apremilast (Otezla), a recently approved oral phosphodiesterase 4 inhibitor, will be a particularly attractive treatment option for many dermatologists and patients, he said at the South Beach Symposium.

Apremilast has a very limited effect on the immune system, and it’s an oral therapy and thus requires no needles. It is very safe – with “strikingly few” serious adverse events – and no laboratory monitoring is required, he explained.

Efficacy results with apremilast are modest. In the phase III ESTEEM trial, for example, 33% of patients achieved at least 75% improvement (PASI-75), compared with 5% of patients who received placebo, said Dr. Pariser of Eastern Virginia Medical School, Norfolk, and an investigator for the trial.

Further, the drug can be used for almost any patient and type of psoriasis; it is an option for those who want systemic therapy, but who don’t want to go on a biologic or methotrexate, and its use is not precluded by a history of cancer or infections, as is the case with biologics, he added.

Apremilast also will be attractive for dermatologists who do not currently prescribe systemic therapy for psoriasis, or who don’t use aggressive systemic therapy for psoriasis, he said.

“If a prescriber feels safety is more important than efficacy, this might be a good choice,” he said.

Secukinumab (Cosentyx), on the other hand, is a “big gun,” Dr. Pariser said of the biologic, which was approved in January 2015 for the treatment of adults with moderate to severe plaque psoriasis.

“It’s the biggest gun we’ve got now … and it really has a safety profile similar to existing biologics so far,” he said.

The fully human monoclonal antibody inhibits interleukin-17A and is administered by subcutaneous injection. Its safety and efficacy were demonstrated in numerous of studies involving about 4,500 patients. Treatment was associated with significant improvement, compared with placebo, said Dr. Pariser, who also was an investigator on secukinumab trials.

Of note, while the PASI-75 findings for secukinumab are “a nice number but not dramatically higher than things we have had in the past,” the PASI-90 and PASI-100 scores are remarkable, he said.

At the highest dose studied (300 mg given at weeks 1, 2, 3, 4, and 8, and monthly thereafter), PASI-90 was achieved by 59% of patients in one study, and PASI-100 was achieved in 28%.

“That’s significant. We haven’t had that before, and that is really, really, really nice,” he said.

Further, the primary efficacy endpoint of the study was outcome at 12 weeks, but patients continued to improve at least until 16 weeks.

PASI-100 – no psoriasis whatsoever – was 40% at 16 weeks, he said.

In another phase III trial, secukinumab was again shown to be superior to placebo, but it also compared favorably with etanercept, he noted.

Safety was reasonable in the secukinumab trials. No deaths occurred, but there were more serious adverse events and discontinuations in the active treatment group. Nasopharyngitis was the most common serious adverse events, and it occurred in all groups. Upper respiratory tract infections appeared to be more common in the secukinumab patients, he noted.

An important consideration with secukinumab, however, is the need for continuous treatment, he said.

“The bottom line, really, is that patients should stay on it. They will lose effectiveness if they go off of it or take it on an as-needed basis,” he said.

Dr. Pariser is a consultant and/or researcher for Amgen, AbbVie, Celgene, Eli Lilly, Janssen Pharmaceuticals, Merck, and Pfizer.

MIAMI BEACH – Two of the newest treatments available for psoriasis – apremilast and secukinumab – are true “game-changers,” according to Dr. David M. Pariser.

Apremilast (Otezla), a recently approved oral phosphodiesterase 4 inhibitor, will be a particularly attractive treatment option for many dermatologists and patients, he said at the South Beach Symposium.

Apremilast has a very limited effect on the immune system, and it’s an oral therapy and thus requires no needles. It is very safe – with “strikingly few” serious adverse events – and no laboratory monitoring is required, he explained.

Efficacy results with apremilast are modest. In the phase III ESTEEM trial, for example, 33% of patients achieved at least 75% improvement (PASI-75), compared with 5% of patients who received placebo, said Dr. Pariser of Eastern Virginia Medical School, Norfolk, and an investigator for the trial.

Further, the drug can be used for almost any patient and type of psoriasis; it is an option for those who want systemic therapy, but who don’t want to go on a biologic or methotrexate, and its use is not precluded by a history of cancer or infections, as is the case with biologics, he added.

Apremilast also will be attractive for dermatologists who do not currently prescribe systemic therapy for psoriasis, or who don’t use aggressive systemic therapy for psoriasis, he said.

“If a prescriber feels safety is more important than efficacy, this might be a good choice,” he said.

Secukinumab (Cosentyx), on the other hand, is a “big gun,” Dr. Pariser said of the biologic, which was approved in January 2015 for the treatment of adults with moderate to severe plaque psoriasis.

“It’s the biggest gun we’ve got now … and it really has a safety profile similar to existing biologics so far,” he said.

The fully human monoclonal antibody inhibits interleukin-17A and is administered by subcutaneous injection. Its safety and efficacy were demonstrated in numerous of studies involving about 4,500 patients. Treatment was associated with significant improvement, compared with placebo, said Dr. Pariser, who also was an investigator on secukinumab trials.

Of note, while the PASI-75 findings for secukinumab are “a nice number but not dramatically higher than things we have had in the past,” the PASI-90 and PASI-100 scores are remarkable, he said.

At the highest dose studied (300 mg given at weeks 1, 2, 3, 4, and 8, and monthly thereafter), PASI-90 was achieved by 59% of patients in one study, and PASI-100 was achieved in 28%.

“That’s significant. We haven’t had that before, and that is really, really, really nice,” he said.

Further, the primary efficacy endpoint of the study was outcome at 12 weeks, but patients continued to improve at least until 16 weeks.

PASI-100 – no psoriasis whatsoever – was 40% at 16 weeks, he said.

In another phase III trial, secukinumab was again shown to be superior to placebo, but it also compared favorably with etanercept, he noted.

Safety was reasonable in the secukinumab trials. No deaths occurred, but there were more serious adverse events and discontinuations in the active treatment group. Nasopharyngitis was the most common serious adverse events, and it occurred in all groups. Upper respiratory tract infections appeared to be more common in the secukinumab patients, he noted.

An important consideration with secukinumab, however, is the need for continuous treatment, he said.

“The bottom line, really, is that patients should stay on it. They will lose effectiveness if they go off of it or take it on an as-needed basis,” he said.

Dr. Pariser is a consultant and/or researcher for Amgen, AbbVie, Celgene, Eli Lilly, Janssen Pharmaceuticals, Merck, and Pfizer.

MIAMI BEACH – Two of the newest treatments available for psoriasis – apremilast and secukinumab – are true “game-changers,” according to Dr. David M. Pariser.

Apremilast (Otezla), a recently approved oral phosphodiesterase 4 inhibitor, will be a particularly attractive treatment option for many dermatologists and patients, he said at the South Beach Symposium.

Apremilast has a very limited effect on the immune system, and it’s an oral therapy and thus requires no needles. It is very safe – with “strikingly few” serious adverse events – and no laboratory monitoring is required, he explained.

Efficacy results with apremilast are modest. In the phase III ESTEEM trial, for example, 33% of patients achieved at least 75% improvement (PASI-75), compared with 5% of patients who received placebo, said Dr. Pariser of Eastern Virginia Medical School, Norfolk, and an investigator for the trial.

Further, the drug can be used for almost any patient and type of psoriasis; it is an option for those who want systemic therapy, but who don’t want to go on a biologic or methotrexate, and its use is not precluded by a history of cancer or infections, as is the case with biologics, he added.

Apremilast also will be attractive for dermatologists who do not currently prescribe systemic therapy for psoriasis, or who don’t use aggressive systemic therapy for psoriasis, he said.

“If a prescriber feels safety is more important than efficacy, this might be a good choice,” he said.

Secukinumab (Cosentyx), on the other hand, is a “big gun,” Dr. Pariser said of the biologic, which was approved in January 2015 for the treatment of adults with moderate to severe plaque psoriasis.

“It’s the biggest gun we’ve got now … and it really has a safety profile similar to existing biologics so far,” he said.

The fully human monoclonal antibody inhibits interleukin-17A and is administered by subcutaneous injection. Its safety and efficacy were demonstrated in numerous of studies involving about 4,500 patients. Treatment was associated with significant improvement, compared with placebo, said Dr. Pariser, who also was an investigator on secukinumab trials.

Of note, while the PASI-75 findings for secukinumab are “a nice number but not dramatically higher than things we have had in the past,” the PASI-90 and PASI-100 scores are remarkable, he said.

At the highest dose studied (300 mg given at weeks 1, 2, 3, 4, and 8, and monthly thereafter), PASI-90 was achieved by 59% of patients in one study, and PASI-100 was achieved in 28%.

“That’s significant. We haven’t had that before, and that is really, really, really nice,” he said.

Further, the primary efficacy endpoint of the study was outcome at 12 weeks, but patients continued to improve at least until 16 weeks.

PASI-100 – no psoriasis whatsoever – was 40% at 16 weeks, he said.

In another phase III trial, secukinumab was again shown to be superior to placebo, but it also compared favorably with etanercept, he noted.

Safety was reasonable in the secukinumab trials. No deaths occurred, but there were more serious adverse events and discontinuations in the active treatment group. Nasopharyngitis was the most common serious adverse events, and it occurred in all groups. Upper respiratory tract infections appeared to be more common in the secukinumab patients, he noted.

An important consideration with secukinumab, however, is the need for continuous treatment, he said.

“The bottom line, really, is that patients should stay on it. They will lose effectiveness if they go off of it or take it on an as-needed basis,” he said.

Dr. Pariser is a consultant and/or researcher for Amgen, AbbVie, Celgene, Eli Lilly, Janssen Pharmaceuticals, Merck, and Pfizer.

MIAMI BEACH – If all else fails in treating psoriasis, a tonsillectomy may do the trick – at least in patients whose psoriasis is associated with recurrent tonsillitis, according to findings from a systematic review of available data.

“Maybe taking the tonsils out removes resident bacteria like strep whose antigens tend to promote psoriasis,” Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston, suggested during a presentation at the South Beach Symposium.

The relationship between streptococcal pharyngitis and guttate psoriasis is well known, he explained during the talk on the latest findings in clinical dermatology.

Indeed, the authors of the systematic review noted that streptococcal infection is associated with psoriasis onset in some patients, but said it was unknown whether tonsillectomy decreases psoriasis symptoms in those patients.

Dr. Tara D. Rachakonda of Salt Lake City and her colleagues included studies dating back to 1960, and identified 20 relevant studies – including 5 controlled studies – involving 545 patients with psoriasis who were evaluated for or underwent tonsillectomy. The overall improvement rate across the studies was about 70% in 410 patients who underwent tonsillectomy, and in one of the studies the response rate was 86%.

In some cases, the response was sustained, but some patients experienced relapse, they reported (JAAD 2015;72:261-75).

The authors concluded that tonsillectomy may be a potential treatment option in patients with recalcitrant psoriasis associated with episodes of tonsillitis, but noted that additional study with long-term follow-up is needed to examine both the extent and persistence of benefit of tonsillectomy in psoriasis patients.

“The evidence is not sufficient to recommend tonsillectomy in all of your psoriasis patients,” Dr. Rosen said, but he noted that it may be something worth considering in patients who still have their tonsils and who are not responding to psoriasis treatments.

Dr. Rosen reported having no relevant financial disclosures.

MIAMI BEACH – If all else fails in treating psoriasis, a tonsillectomy may do the trick – at least in patients whose psoriasis is associated with recurrent tonsillitis, according to findings from a systematic review of available data.

“Maybe taking the tonsils out removes resident bacteria like strep whose antigens tend to promote psoriasis,” Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston, suggested during a presentation at the South Beach Symposium.

The relationship between streptococcal pharyngitis and guttate psoriasis is well known, he explained during the talk on the latest findings in clinical dermatology.

Indeed, the authors of the systematic review noted that streptococcal infection is associated with psoriasis onset in some patients, but said it was unknown whether tonsillectomy decreases psoriasis symptoms in those patients.

Dr. Tara D. Rachakonda of Salt Lake City and her colleagues included studies dating back to 1960, and identified 20 relevant studies – including 5 controlled studies – involving 545 patients with psoriasis who were evaluated for or underwent tonsillectomy. The overall improvement rate across the studies was about 70% in 410 patients who underwent tonsillectomy, and in one of the studies the response rate was 86%.

In some cases, the response was sustained, but some patients experienced relapse, they reported (JAAD 2015;72:261-75).

The authors concluded that tonsillectomy may be a potential treatment option in patients with recalcitrant psoriasis associated with episodes of tonsillitis, but noted that additional study with long-term follow-up is needed to examine both the extent and persistence of benefit of tonsillectomy in psoriasis patients.

“The evidence is not sufficient to recommend tonsillectomy in all of your psoriasis patients,” Dr. Rosen said, but he noted that it may be something worth considering in patients who still have their tonsils and who are not responding to psoriasis treatments.

Dr. Rosen reported having no relevant financial disclosures.

MIAMI BEACH – If all else fails in treating psoriasis, a tonsillectomy may do the trick – at least in patients whose psoriasis is associated with recurrent tonsillitis, according to findings from a systematic review of available data.

“Maybe taking the tonsils out removes resident bacteria like strep whose antigens tend to promote psoriasis,” Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston, suggested during a presentation at the South Beach Symposium.

The relationship between streptococcal pharyngitis and guttate psoriasis is well known, he explained during the talk on the latest findings in clinical dermatology.

Indeed, the authors of the systematic review noted that streptococcal infection is associated with psoriasis onset in some patients, but said it was unknown whether tonsillectomy decreases psoriasis symptoms in those patients.

Dr. Tara D. Rachakonda of Salt Lake City and her colleagues included studies dating back to 1960, and identified 20 relevant studies – including 5 controlled studies – involving 545 patients with psoriasis who were evaluated for or underwent tonsillectomy. The overall improvement rate across the studies was about 70% in 410 patients who underwent tonsillectomy, and in one of the studies the response rate was 86%.

In some cases, the response was sustained, but some patients experienced relapse, they reported (JAAD 2015;72:261-75).

The authors concluded that tonsillectomy may be a potential treatment option in patients with recalcitrant psoriasis associated with episodes of tonsillitis, but noted that additional study with long-term follow-up is needed to examine both the extent and persistence of benefit of tonsillectomy in psoriasis patients.

“The evidence is not sufficient to recommend tonsillectomy in all of your psoriasis patients,” Dr. Rosen said, but he noted that it may be something worth considering in patients who still have their tonsils and who are not responding to psoriasis treatments.

Dr. Rosen reported having no relevant financial disclosures.

Patients with chronic plaque psoriasis who were given ixekizumab improved the severity of scalp and nail lesions in a phase 2 trial, according to Dr. Richard G. Langley of Dalhousie University in Halifax, N.S., and his associates.

In a 20-week randomized, placebo-controlled trial, 142 patients with moderate to severe plaque psoriasis at baseline were injected subcutaneously with ixekizumab at weeks 0, 2, 4, 8, 12, and 16. Ixekizumab, a monoclonal antibody, specifically targets IL-17A, a cytokine involved in the development of psoriasis.

Patients with scalp psoriasis were split into groups and given 10-, 25-, 75- and 150-mg doses of ixekizumab, or placebo; patients with nail psoriasis received 75- and 150-mg doses of ixekizumab. After 20 weeks, patients scalp psoriasis patients in the 25-, 75-, and 150-mg groups and nail psoriasis patients in the 75- and 150-mg groups showed significant improvement from baseline. By week 48, 78% of patients with scalp psoriasis and 51% of patients with nail psoriasis experienced complete resolution of lesions, the investigators reported.

Read the full article in the Journal of the European Academy of Dermatology and Venereology.

Patients with chronic plaque psoriasis who were given ixekizumab improved the severity of scalp and nail lesions in a phase 2 trial, according to Dr. Richard G. Langley of Dalhousie University in Halifax, N.S., and his associates.

In a 20-week randomized, placebo-controlled trial, 142 patients with moderate to severe plaque psoriasis at baseline were injected subcutaneously with ixekizumab at weeks 0, 2, 4, 8, 12, and 16. Ixekizumab, a monoclonal antibody, specifically targets IL-17A, a cytokine involved in the development of psoriasis.

Patients with scalp psoriasis were split into groups and given 10-, 25-, 75- and 150-mg doses of ixekizumab, or placebo; patients with nail psoriasis received 75- and 150-mg doses of ixekizumab. After 20 weeks, patients scalp psoriasis patients in the 25-, 75-, and 150-mg groups and nail psoriasis patients in the 75- and 150-mg groups showed significant improvement from baseline. By week 48, 78% of patients with scalp psoriasis and 51% of patients with nail psoriasis experienced complete resolution of lesions, the investigators reported.

Read the full article in the Journal of the European Academy of Dermatology and Venereology.

Patients with chronic plaque psoriasis who were given ixekizumab improved the severity of scalp and nail lesions in a phase 2 trial, according to Dr. Richard G. Langley of Dalhousie University in Halifax, N.S., and his associates.

In a 20-week randomized, placebo-controlled trial, 142 patients with moderate to severe plaque psoriasis at baseline were injected subcutaneously with ixekizumab at weeks 0, 2, 4, 8, 12, and 16. Ixekizumab, a monoclonal antibody, specifically targets IL-17A, a cytokine involved in the development of psoriasis.

Patients with scalp psoriasis were split into groups and given 10-, 25-, 75- and 150-mg doses of ixekizumab, or placebo; patients with nail psoriasis received 75- and 150-mg doses of ixekizumab. After 20 weeks, patients scalp psoriasis patients in the 25-, 75-, and 150-mg groups and nail psoriasis patients in the 75- and 150-mg groups showed significant improvement from baseline. By week 48, 78% of patients with scalp psoriasis and 51% of patients with nail psoriasis experienced complete resolution of lesions, the investigators reported.

Read the full article in the Journal of the European Academy of Dermatology and Venereology.

Patients with axial spondyloarthritis who smoke and have elevated C-reactive protein levels respond less well to anti–tumor necrosis factor treatment than do nonsmokers, Swiss researchers reported.

The influence of smoking on treatment response is well known in rheumatoid arthritis, but the impact of tobacco use on patients with axial spondyloarthritis is only beginning to emerge.

©pmphoto/iStockphoto.com

In this study of 698 patients with confirmed axial spondyloarthritis who were taking a first anti–tumor necrosis factor (TNF) agent, the effect of smoking on treatment response was measured at 1 year using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) after adjustment for potential confounders, such as sex, amount of exercise, age, and disease duration (Ann. Rheum. Dis. 2015 Feb. 9 [doi:10.1136/annrheumdis-2013-205133]).

Dr. Adrian Ciurea of the University Hospital Zurich and associates found that patients with elevated C-reactive protein (CRP) levels who smoked achieved significantly smaller reductions in BASDAI and ASDAS scores after initiation of TNF inhibitors, compared with nonsmokers (0.75 BASDAI and 0.69 ASDAS units less, P = .005 and P = .001, respectively).

The odds of reaching a 50% improvement in BASDAI score or meeting ASAS criteria for 40% improvement after 1 year was significantly lower in current smokers than in nonsmokers (odds ratio, 0.54; P = .03; and OR, 0.43; P = .004, respectively).

Past smoking had no significant effect on response to treatment, the researchers said.

The underlying mechanisms on the influence of smoking are unclear, but could be related to an interference with the pharmacokinetics of anti-TNFs or smoking may increase pain levels or starve tissues of oxygen, the researchers suggested.

“Whether quitting smoking might ameliorate the course of disease during treatment with TNFi remains to be confirmed in prospective studies,” they concluded.

Patients in the study were part of the Swiss Clinical Quality Management Cohort during 2005-2014. Almost two-thirds (62%) were smokers; 38% were nonsmokers.

Dr. Ciurea and two coauthors have received consulting and/or speaking fees from a variety of companies marketing biologic drugs for rheumatic diseases. The study was funded by grants from the Foundation for Arthritis Research and the Swiss Spondylitis Foundation.

Patients with axial spondyloarthritis who smoke and have elevated C-reactive protein levels respond less well to anti–tumor necrosis factor treatment than do nonsmokers, Swiss researchers reported.

The influence of smoking on treatment response is well known in rheumatoid arthritis, but the impact of tobacco use on patients with axial spondyloarthritis is only beginning to emerge.

©pmphoto/iStockphoto.com

In this study of 698 patients with confirmed axial spondyloarthritis who were taking a first anti–tumor necrosis factor (TNF) agent, the effect of smoking on treatment response was measured at 1 year using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) after adjustment for potential confounders, such as sex, amount of exercise, age, and disease duration (Ann. Rheum. Dis. 2015 Feb. 9 [doi:10.1136/annrheumdis-2013-205133]).

Dr. Adrian Ciurea of the University Hospital Zurich and associates found that patients with elevated C-reactive protein (CRP) levels who smoked achieved significantly smaller reductions in BASDAI and ASDAS scores after initiation of TNF inhibitors, compared with nonsmokers (0.75 BASDAI and 0.69 ASDAS units less, P = .005 and P = .001, respectively).

The odds of reaching a 50% improvement in BASDAI score or meeting ASAS criteria for 40% improvement after 1 year was significantly lower in current smokers than in nonsmokers (odds ratio, 0.54; P = .03; and OR, 0.43; P = .004, respectively).

Past smoking had no significant effect on response to treatment, the researchers said.

The underlying mechanisms on the influence of smoking are unclear, but could be related to an interference with the pharmacokinetics of anti-TNFs or smoking may increase pain levels or starve tissues of oxygen, the researchers suggested.

“Whether quitting smoking might ameliorate the course of disease during treatment with TNFi remains to be confirmed in prospective studies,” they concluded.

Patients in the study were part of the Swiss Clinical Quality Management Cohort during 2005-2014. Almost two-thirds (62%) were smokers; 38% were nonsmokers.

Dr. Ciurea and two coauthors have received consulting and/or speaking fees from a variety of companies marketing biologic drugs for rheumatic diseases. The study was funded by grants from the Foundation for Arthritis Research and the Swiss Spondylitis Foundation.

Patients with axial spondyloarthritis who smoke and have elevated C-reactive protein levels respond less well to anti–tumor necrosis factor treatment than do nonsmokers, Swiss researchers reported.

The influence of smoking on treatment response is well known in rheumatoid arthritis, but the impact of tobacco use on patients with axial spondyloarthritis is only beginning to emerge.

©pmphoto/iStockphoto.com

In this study of 698 patients with confirmed axial spondyloarthritis who were taking a first anti–tumor necrosis factor (TNF) agent, the effect of smoking on treatment response was measured at 1 year using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) after adjustment for potential confounders, such as sex, amount of exercise, age, and disease duration (Ann. Rheum. Dis. 2015 Feb. 9 [doi:10.1136/annrheumdis-2013-205133]).

Dr. Adrian Ciurea of the University Hospital Zurich and associates found that patients with elevated C-reactive protein (CRP) levels who smoked achieved significantly smaller reductions in BASDAI and ASDAS scores after initiation of TNF inhibitors, compared with nonsmokers (0.75 BASDAI and 0.69 ASDAS units less, P = .005 and P = .001, respectively).

The odds of reaching a 50% improvement in BASDAI score or meeting ASAS criteria for 40% improvement after 1 year was significantly lower in current smokers than in nonsmokers (odds ratio, 0.54; P = .03; and OR, 0.43; P = .004, respectively).

Past smoking had no significant effect on response to treatment, the researchers said.

The underlying mechanisms on the influence of smoking are unclear, but could be related to an interference with the pharmacokinetics of anti-TNFs or smoking may increase pain levels or starve tissues of oxygen, the researchers suggested.

“Whether quitting smoking might ameliorate the course of disease during treatment with TNFi remains to be confirmed in prospective studies,” they concluded.

Patients in the study were part of the Swiss Clinical Quality Management Cohort during 2005-2014. Almost two-thirds (62%) were smokers; 38% were nonsmokers.

Dr. Ciurea and two coauthors have received consulting and/or speaking fees from a variety of companies marketing biologic drugs for rheumatic diseases. The study was funded by grants from the Foundation for Arthritis Research and the Swiss Spondylitis Foundation.

Several genetic risk loci unique to psoriatic arthritis have been identified in a study of samples from 1,962 patients with the disease and 8,923 healthy population controls of white ancestry, according to Dr. John Bowes and his associates.

The investigators used Immunochip genotyping array to fine map previously reported immune-related susceptibility loci, including known psoriasis susceptibility loci, to identify novel psoriatic arthritis (PsA) susceptibility loci.

They found a risk locus specific to PsA at chromosome 5q31, and they detected PsA risk variants at chromosome 1q31, a known psoriasis susceptibility locus. They found independent associations between PsA and three human leukocyte antigen (HLA) genes as well as three non-HLA loci. Finally, they determined that the PsA genetic risk variants preferentially associated with epigenetic markers of open chromatin in CD8+ memory primary T cells, supporting “their importance in the underlying disease mechanism.”

Until this point, the majority of risk loci associated with PsA were shared with psoriasis, but the discovery of unique risk loci could begin to explain fundamental differences between psoriasis and PsA, the investigators said.

Read the full study published Feb. 5 in Nature Communications (doi:10.1038/ncomms7046).

Several genetic risk loci unique to psoriatic arthritis have been identified in a study of samples from 1,962 patients with the disease and 8,923 healthy population controls of white ancestry, according to Dr. John Bowes and his associates.

The investigators used Immunochip genotyping array to fine map previously reported immune-related susceptibility loci, including known psoriasis susceptibility loci, to identify novel psoriatic arthritis (PsA) susceptibility loci.

They found a risk locus specific to PsA at chromosome 5q31, and they detected PsA risk variants at chromosome 1q31, a known psoriasis susceptibility locus. They found independent associations between PsA and three human leukocyte antigen (HLA) genes as well as three non-HLA loci. Finally, they determined that the PsA genetic risk variants preferentially associated with epigenetic markers of open chromatin in CD8+ memory primary T cells, supporting “their importance in the underlying disease mechanism.”

Until this point, the majority of risk loci associated with PsA were shared with psoriasis, but the discovery of unique risk loci could begin to explain fundamental differences between psoriasis and PsA, the investigators said.

Read the full study published Feb. 5 in Nature Communications (doi:10.1038/ncomms7046).

Several genetic risk loci unique to psoriatic arthritis have been identified in a study of samples from 1,962 patients with the disease and 8,923 healthy population controls of white ancestry, according to Dr. John Bowes and his associates.

The investigators used Immunochip genotyping array to fine map previously reported immune-related susceptibility loci, including known psoriasis susceptibility loci, to identify novel psoriatic arthritis (PsA) susceptibility loci.

They found a risk locus specific to PsA at chromosome 5q31, and they detected PsA risk variants at chromosome 1q31, a known psoriasis susceptibility locus. They found independent associations between PsA and three human leukocyte antigen (HLA) genes as well as three non-HLA loci. Finally, they determined that the PsA genetic risk variants preferentially associated with epigenetic markers of open chromatin in CD8+ memory primary T cells, supporting “their importance in the underlying disease mechanism.”

Until this point, the majority of risk loci associated with PsA were shared with psoriasis, but the discovery of unique risk loci could begin to explain fundamental differences between psoriasis and PsA, the investigators said.

Read the full study published Feb. 5 in Nature Communications (doi:10.1038/ncomms7046).