Ankylosing spondylitis

The presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA), according to recent research.

The findings suggest HLA-B27-positive patients have worse radiographic damage, more typical marginal syndesmophytes, and a greater number of bilateral fused sacroiliac joints in the spine, reported Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues. Their report was published in Arthritis Care & Research.

“In order to achieve phenotypic diversity, we studied patients with PsA [psoriatic arthritis] and axial involvement (a group of patients recognized to have less frequent carriage of HLA-B27), and AS [ankylosing spondylitis],” they wrote.

The researchers conducted a multicenter, cross-sectional cohort study involving 198 patients with AS and 244 with PsA. Various clinical, radiographic, and laboratory data were collected from databases in Ireland, Spain, Germany, Russia, Canada, and Italy.

HLA-B27-positive patients were older (mean 49.1 years vs. 53.8 years), were more often male (73% vs. 59%), and had longer disease duration (mean 13.6 years vs. 11.0 years).

The team compared HLA-B27 carriers and noncarriers on syndesmophyte morphology, the symmetry of the sacroiliac joints and syndesmophytes, in addition to radiographic damage, as measured by the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA Spondylitis Radiology Index (PASRI).

After analysis, the researchers found that HLA-B27 positivity was associated with higher median mSASSS (6 vs. 2; P = .04) and PASRI scores (12 vs. 6; P less than .0001), marginal syndesmophytes (odds ratio, 1.97; 95% confidence interval, 1.16-3.36), and syndesmophyte symmetry (OR, 3.02; 95% CI, 1.38-6.61).

“[Our] study [showed] no difference in sacroiliac symmetry, and no difference in nonmarginal syndesmophytes, according to HLA-B27 status,” they reported.

In addition, they reported that male sex (OR, 1.66; 95% CI, 1.04-2.66) and age (OR, 1.08; 95% CI, 1.05-1.10) were positive predictors of marginal syndesmophytes.

In contrast, only male sex (OR, 2.55; 95% CI, 1.46-4.64) and age (OR, 1.05; 95% CI, 1.03-1.07) predicted the presence of nonmarginal syndesmophytes.

The researchers acknowledged that two key limitations of the study were the absence of disease-group matching and lack of independent central reading of radiographs.

“This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously found but emphasizes the importance of HLA-B27 status in severity and the phenotypic expression of disease radiographically,” they concluded.

The study was funded by the Academy of Medical Sciences (U.K.). The authors reported having no conflicts of interest.

SOURCE: Coates LC et al. Arthritis Care Res. 2020 Feb 26. doi: 10.1002/acr.24174.

The presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA), according to recent research.

The findings suggest HLA-B27-positive patients have worse radiographic damage, more typical marginal syndesmophytes, and a greater number of bilateral fused sacroiliac joints in the spine, reported Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues. Their report was published in Arthritis Care & Research.

“In order to achieve phenotypic diversity, we studied patients with PsA [psoriatic arthritis] and axial involvement (a group of patients recognized to have less frequent carriage of HLA-B27), and AS [ankylosing spondylitis],” they wrote.

The researchers conducted a multicenter, cross-sectional cohort study involving 198 patients with AS and 244 with PsA. Various clinical, radiographic, and laboratory data were collected from databases in Ireland, Spain, Germany, Russia, Canada, and Italy.

HLA-B27-positive patients were older (mean 49.1 years vs. 53.8 years), were more often male (73% vs. 59%), and had longer disease duration (mean 13.6 years vs. 11.0 years).

The team compared HLA-B27 carriers and noncarriers on syndesmophyte morphology, the symmetry of the sacroiliac joints and syndesmophytes, in addition to radiographic damage, as measured by the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA Spondylitis Radiology Index (PASRI).

After analysis, the researchers found that HLA-B27 positivity was associated with higher median mSASSS (6 vs. 2; P = .04) and PASRI scores (12 vs. 6; P less than .0001), marginal syndesmophytes (odds ratio, 1.97; 95% confidence interval, 1.16-3.36), and syndesmophyte symmetry (OR, 3.02; 95% CI, 1.38-6.61).

“[Our] study [showed] no difference in sacroiliac symmetry, and no difference in nonmarginal syndesmophytes, according to HLA-B27 status,” they reported.

In addition, they reported that male sex (OR, 1.66; 95% CI, 1.04-2.66) and age (OR, 1.08; 95% CI, 1.05-1.10) were positive predictors of marginal syndesmophytes.

In contrast, only male sex (OR, 2.55; 95% CI, 1.46-4.64) and age (OR, 1.05; 95% CI, 1.03-1.07) predicted the presence of nonmarginal syndesmophytes.

The researchers acknowledged that two key limitations of the study were the absence of disease-group matching and lack of independent central reading of radiographs.

“This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously found but emphasizes the importance of HLA-B27 status in severity and the phenotypic expression of disease radiographically,” they concluded.

The study was funded by the Academy of Medical Sciences (U.K.). The authors reported having no conflicts of interest.

SOURCE: Coates LC et al. Arthritis Care Res. 2020 Feb 26. doi: 10.1002/acr.24174.

The presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA), according to recent research.

The findings suggest HLA-B27-positive patients have worse radiographic damage, more typical marginal syndesmophytes, and a greater number of bilateral fused sacroiliac joints in the spine, reported Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues. Their report was published in Arthritis Care & Research.

“In order to achieve phenotypic diversity, we studied patients with PsA [psoriatic arthritis] and axial involvement (a group of patients recognized to have less frequent carriage of HLA-B27), and AS [ankylosing spondylitis],” they wrote.

The researchers conducted a multicenter, cross-sectional cohort study involving 198 patients with AS and 244 with PsA. Various clinical, radiographic, and laboratory data were collected from databases in Ireland, Spain, Germany, Russia, Canada, and Italy.

HLA-B27-positive patients were older (mean 49.1 years vs. 53.8 years), were more often male (73% vs. 59%), and had longer disease duration (mean 13.6 years vs. 11.0 years).

The team compared HLA-B27 carriers and noncarriers on syndesmophyte morphology, the symmetry of the sacroiliac joints and syndesmophytes, in addition to radiographic damage, as measured by the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA Spondylitis Radiology Index (PASRI).

After analysis, the researchers found that HLA-B27 positivity was associated with higher median mSASSS (6 vs. 2; P = .04) and PASRI scores (12 vs. 6; P less than .0001), marginal syndesmophytes (odds ratio, 1.97; 95% confidence interval, 1.16-3.36), and syndesmophyte symmetry (OR, 3.02; 95% CI, 1.38-6.61).

“[Our] study [showed] no difference in sacroiliac symmetry, and no difference in nonmarginal syndesmophytes, according to HLA-B27 status,” they reported.

In addition, they reported that male sex (OR, 1.66; 95% CI, 1.04-2.66) and age (OR, 1.08; 95% CI, 1.05-1.10) were positive predictors of marginal syndesmophytes.

In contrast, only male sex (OR, 2.55; 95% CI, 1.46-4.64) and age (OR, 1.05; 95% CI, 1.03-1.07) predicted the presence of nonmarginal syndesmophytes.

The researchers acknowledged that two key limitations of the study were the absence of disease-group matching and lack of independent central reading of radiographs.

“This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously found but emphasizes the importance of HLA-B27 status in severity and the phenotypic expression of disease radiographically,” they concluded.

The study was funded by the Academy of Medical Sciences (U.K.). The authors reported having no conflicts of interest.

SOURCE: Coates LC et al. Arthritis Care Res. 2020 Feb 26. doi: 10.1002/acr.24174.

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

[email protected]

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

[email protected]

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

[email protected]

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.

We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.

Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.

The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.

We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.

Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.

The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.

We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.

Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.

ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.

Sharon Worcester/MDedge News

When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
 

C-VIEW

In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.

This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.

The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.

Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.

“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.

Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.

Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.

“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”

AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.

The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.

“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.

C-axSpAnd

In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.

The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.

The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.

For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.

Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.

Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.

Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.

Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.

The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.

“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.

The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.

The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.

[email protected]

SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.

ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.

Sharon Worcester/MDedge News

When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
 

C-VIEW

In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.

This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.

The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.

Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.

“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.

Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.

Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.

“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”

AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.

The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.

“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.

C-axSpAnd

In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.

The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.

The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.

For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.

Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.

Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.

Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.

Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.

The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.

“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.

The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.

The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.

[email protected]

SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.

ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.

Sharon Worcester/MDedge News

When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
 

C-VIEW

In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.

This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.

The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.

Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.

“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.

Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.

Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.

“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”

AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.

The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.

“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.

C-axSpAnd

In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.

The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.

The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.

For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.

Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.

Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.

Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.

Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.

The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.

“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.

The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.

The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.

[email protected]

SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.