Rheumatology

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

Treatment of osteoporosis in older adults at increased risk for fractures declined from 2010 to 2014, based on a study of nearly 900,000 individuals.

Courtesy University of Alabama at Birmingham

Osteoporotic fractures are associated with morbidity and mortality, functional decline, increased nursing home admissions, and a significant economic burden, Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the American College of Rheumatology.

“The number of Americans at risk for fractures on the basis of having osteoporosis is expected to increase by 32% based on the graying of the population,” he said. “Underdiagnosis and undertreatment may be contributing to the increased burden that we are starting to see,” he added.

To assess the impact of osteoporosis management on patients at increased risk for fractures, Dr. Curtis and his colleagues examined temporal trends over 5 years from 885,676 Medicare fee-for-service members with a closed fragility (or osteoporosis-related) fracture between Jan. 1, 2010, and Dec. 31, 2014. The average age of the patients was 81 years; 91% were white, and 94% were women.

The researchers used diagnosis and procedure codes to create an algorithm with a positive predictive value of more than 90%. Individuals with Paget’s disease or a malignancy other than nonmelanoma skin cancer at baseline were excluded.

Overall, use of dual x-ray absorptiometry (DXA) screening in this high-risk population decreased over the study period, with rates during 2010-2014 of 25%, 24%, 23%, 22%, and 16%, respectively. The presence of an osteoporosis diagnosis in the study population decreased over the same period, with rates of 7%, 6%, 6%, 5%, and 4%, respectively. In addition, the percentage of high-risk patients undergoing osteoporosis treatment at the time of fracture during 2010-2014 was 29%, 24%, 20%, 16%, and 11%, respectively.

Despite their history of fracture, more than half of individuals in each year’s database had a comorbidity or were taking a medication that increased fall risk. The most common comorbidity was impaired mobility (about 20% of each yearly cohort), followed by history of falls, history of stroke, impaired vision, muscle atrophy or weakness, and Parkinson’s disease. Approximately half of the patients in each year’s group were taking opioids, and approximately 20% were taking oral corticosteroids.

The findings were limited by several factors, including those common to studies involving administrative claims databases, such as a lack of complete medical and treatment history, lack of diagnostic validation for osteoporosis-related fractures, and lack of information on why use of DXA decreased over time, Dr. Curtis said. However, the results show the need to improve management of individuals at increased risk for falls and fractures to reduce not only the risk of morbidity and mortality, but also the economic impact.

Dr. Curtis disclosed serving as a consultant for Radius Health and Amgen, and the University of Alabama at Birmingham Medical Center received grants from these companies.

SOURCE: Curtis et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1872.

Treatment of osteoporosis in older adults at increased risk for fractures declined from 2010 to 2014, based on a study of nearly 900,000 individuals.

Courtesy University of Alabama at Birmingham

Osteoporotic fractures are associated with morbidity and mortality, functional decline, increased nursing home admissions, and a significant economic burden, Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the American College of Rheumatology.

“The number of Americans at risk for fractures on the basis of having osteoporosis is expected to increase by 32% based on the graying of the population,” he said. “Underdiagnosis and undertreatment may be contributing to the increased burden that we are starting to see,” he added.

To assess the impact of osteoporosis management on patients at increased risk for fractures, Dr. Curtis and his colleagues examined temporal trends over 5 years from 885,676 Medicare fee-for-service members with a closed fragility (or osteoporosis-related) fracture between Jan. 1, 2010, and Dec. 31, 2014. The average age of the patients was 81 years; 91% were white, and 94% were women.

The researchers used diagnosis and procedure codes to create an algorithm with a positive predictive value of more than 90%. Individuals with Paget’s disease or a malignancy other than nonmelanoma skin cancer at baseline were excluded.

Overall, use of dual x-ray absorptiometry (DXA) screening in this high-risk population decreased over the study period, with rates during 2010-2014 of 25%, 24%, 23%, 22%, and 16%, respectively. The presence of an osteoporosis diagnosis in the study population decreased over the same period, with rates of 7%, 6%, 6%, 5%, and 4%, respectively. In addition, the percentage of high-risk patients undergoing osteoporosis treatment at the time of fracture during 2010-2014 was 29%, 24%, 20%, 16%, and 11%, respectively.

Despite their history of fracture, more than half of individuals in each year’s database had a comorbidity or were taking a medication that increased fall risk. The most common comorbidity was impaired mobility (about 20% of each yearly cohort), followed by history of falls, history of stroke, impaired vision, muscle atrophy or weakness, and Parkinson’s disease. Approximately half of the patients in each year’s group were taking opioids, and approximately 20% were taking oral corticosteroids.

The findings were limited by several factors, including those common to studies involving administrative claims databases, such as a lack of complete medical and treatment history, lack of diagnostic validation for osteoporosis-related fractures, and lack of information on why use of DXA decreased over time, Dr. Curtis said. However, the results show the need to improve management of individuals at increased risk for falls and fractures to reduce not only the risk of morbidity and mortality, but also the economic impact.

Dr. Curtis disclosed serving as a consultant for Radius Health and Amgen, and the University of Alabama at Birmingham Medical Center received grants from these companies.

SOURCE: Curtis et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1872.

Treatment of osteoporosis in older adults at increased risk for fractures declined from 2010 to 2014, based on a study of nearly 900,000 individuals.

Courtesy University of Alabama at Birmingham

Osteoporotic fractures are associated with morbidity and mortality, functional decline, increased nursing home admissions, and a significant economic burden, Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the American College of Rheumatology.

“The number of Americans at risk for fractures on the basis of having osteoporosis is expected to increase by 32% based on the graying of the population,” he said. “Underdiagnosis and undertreatment may be contributing to the increased burden that we are starting to see,” he added.

To assess the impact of osteoporosis management on patients at increased risk for fractures, Dr. Curtis and his colleagues examined temporal trends over 5 years from 885,676 Medicare fee-for-service members with a closed fragility (or osteoporosis-related) fracture between Jan. 1, 2010, and Dec. 31, 2014. The average age of the patients was 81 years; 91% were white, and 94% were women.

The researchers used diagnosis and procedure codes to create an algorithm with a positive predictive value of more than 90%. Individuals with Paget’s disease or a malignancy other than nonmelanoma skin cancer at baseline were excluded.

Overall, use of dual x-ray absorptiometry (DXA) screening in this high-risk population decreased over the study period, with rates during 2010-2014 of 25%, 24%, 23%, 22%, and 16%, respectively. The presence of an osteoporosis diagnosis in the study population decreased over the same period, with rates of 7%, 6%, 6%, 5%, and 4%, respectively. In addition, the percentage of high-risk patients undergoing osteoporosis treatment at the time of fracture during 2010-2014 was 29%, 24%, 20%, 16%, and 11%, respectively.

Despite their history of fracture, more than half of individuals in each year’s database had a comorbidity or were taking a medication that increased fall risk. The most common comorbidity was impaired mobility (about 20% of each yearly cohort), followed by history of falls, history of stroke, impaired vision, muscle atrophy or weakness, and Parkinson’s disease. Approximately half of the patients in each year’s group were taking opioids, and approximately 20% were taking oral corticosteroids.

The findings were limited by several factors, including those common to studies involving administrative claims databases, such as a lack of complete medical and treatment history, lack of diagnostic validation for osteoporosis-related fractures, and lack of information on why use of DXA decreased over time, Dr. Curtis said. However, the results show the need to improve management of individuals at increased risk for falls and fractures to reduce not only the risk of morbidity and mortality, but also the economic impact.

Dr. Curtis disclosed serving as a consultant for Radius Health and Amgen, and the University of Alabama at Birmingham Medical Center received grants from these companies.

SOURCE: Curtis et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1872.

ATLANTA – Use of high-concentration topical capsaicin was associated with reduced pain, a longer duration of clinical response, and was well tolerated in patients with knee osteoarthritis, compared with lower concentrations of capsaicin and placebo, according to recent research presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

While the ACR has recommended topical capsaicin for the relief of hand and knee OA pain, there are issues with using low-dose capsaicin, including the need for multiple applications and burning, stinging sensations at applications sites. As repeat exposure to capsaicin results in depletion of pain neurotransmitters and a reduction in nerve fibers in a dose-dependent fashion, higher doses of topical capsaicin are a potential topical treatment for OA pain relief, but their tolerability is low, Tim Warneke, vice president of clinical operations at Vizuri Health Sciences in Columbia, Md., said in his presentation.

“[P]oor tolerability has limited the ability to maximize the analgesic effect of capsaicin,” Mr. Warneke said. “While [over-the-counter] preparations of capsaicin provide some pain relief, poor tolerability with higher doses has really left us wondering if we haven’t maximized capsaicin’s ability to provide pain relief.”

Mr. Warneke and colleagues conducted a phase 2, multicenter, double-blind, parallel-group, vehicle-controlled trial where 120 patients with knee OA were randomized in a 1:1:1 ratio to receive 5% capsaicin topical liquid (CGS-200-5), 1% capsaicin topical liquid (CGS-200-1), or vehicle (CGS-200-0) and then followed up to 90 days. “The CGS-200 vehicle was developed to mitigate the burning, stinging pain of capsaicin,” Mr. Warneke said. “It allows the 5% concentration to be well tolerated, which opens the door for increased efficacy, including durability of response.”

Inclusion criteria were radiographically confirmed knee OA using 1986 ACR classification criteria, a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 250 mm or greater, and more than 3 months of chronic knee pain. While patients were excluded for use of topical, oral, or injectable corticosteroids in the month prior to enrollment, they were allowed to continue using analgesics such as NSAIDs if they maintained their daily dose throughout the trial. Mr. Warneke noted the study population was typical of an OA population with a mostly female, mostly Caucasian cohort who had a median age of 60 years and a body mass index of 30 kg/m². Patients had moderate to severe OA and were refractory to previous pain treatments.

The interventions consisted of a single 60-minute application of capsaicin or vehicle to both knees once per day for 4 consecutive days, and patients performed the applications in the clinic. The investigators compared change in WOMAC pain scores between the groups at 31 days, 60 days, and 90 days post dose.

The results at 31 days showed a 46.2% reduction in WOMAC pain scores from baseline for patients using CGS-200-5, compared with a 28.3% reduction in the vehicle group (P = .02). At 60 days, there was a 49.1% reduction in WOMAC pain scores in the CGS-200-5 group, compared with 21.5% in patients using vehicle (P = .0001), and a 42.8% reduction for patients in the CGS-200-5 group at 90 days, compared with 22.8% in the vehicle group (P = .01). The CGS-200-1 group did not reach the primary efficacy WOMAC pain endpoint, compared with vehicle.

A post hoc analysis showed that there was a significantly greater mean reduction in WOMAC total score for patients using CGS-200-5, compared with vehicle at 31 days (P = .02), 60 days (P = .0005), and 90 days post dose (P = .005). “This durability of clinical response for single applications seems to be a promising feature of CGS-200-5,” Mr. Warneke said.

Concerning safety and tolerability, there were no serious adverse events, and one patient discontinued treatment in the CGS-200-5 group. When assessing tolerability at predose, 15-minute, 30-minute, 60-minute, and 90-minute postdose time intervals, the investigators found patients experienced mild or moderate adverse events such as erythema, edema, scaling, and pruritus, with symptoms decreasing by the fourth consecutive day of application.

Mr. Warneke acknowledged the “robust placebo response” in the trial and noted it is not unusual to see in pain studies. “It’s something that is a challenge for all of us who are in this space to overcome, but we still have significant differences here and they are statistically significant as well,” he said. “You have to be pretty good these days to beat the wonder drug placebo, it appears.”

Four authors in addition to Mr. Warneke reported being employees of Vizuri Health Sciences, the company developing CGS-200-5. One author reported being a former consultant for Vizuri. Three authors reported they were current or former employees of CT Clinical Trial & Consulting, a contract research organization employed by Vizuri to execute and manage the study, perform data analysis, and create reports.

SOURCE: Warneke T et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2760.

ATLANTA – Use of high-concentration topical capsaicin was associated with reduced pain, a longer duration of clinical response, and was well tolerated in patients with knee osteoarthritis, compared with lower concentrations of capsaicin and placebo, according to recent research presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

While the ACR has recommended topical capsaicin for the relief of hand and knee OA pain, there are issues with using low-dose capsaicin, including the need for multiple applications and burning, stinging sensations at applications sites. As repeat exposure to capsaicin results in depletion of pain neurotransmitters and a reduction in nerve fibers in a dose-dependent fashion, higher doses of topical capsaicin are a potential topical treatment for OA pain relief, but their tolerability is low, Tim Warneke, vice president of clinical operations at Vizuri Health Sciences in Columbia, Md., said in his presentation.

“[P]oor tolerability has limited the ability to maximize the analgesic effect of capsaicin,” Mr. Warneke said. “While [over-the-counter] preparations of capsaicin provide some pain relief, poor tolerability with higher doses has really left us wondering if we haven’t maximized capsaicin’s ability to provide pain relief.”

Mr. Warneke and colleagues conducted a phase 2, multicenter, double-blind, parallel-group, vehicle-controlled trial where 120 patients with knee OA were randomized in a 1:1:1 ratio to receive 5% capsaicin topical liquid (CGS-200-5), 1% capsaicin topical liquid (CGS-200-1), or vehicle (CGS-200-0) and then followed up to 90 days. “The CGS-200 vehicle was developed to mitigate the burning, stinging pain of capsaicin,” Mr. Warneke said. “It allows the 5% concentration to be well tolerated, which opens the door for increased efficacy, including durability of response.”

Inclusion criteria were radiographically confirmed knee OA using 1986 ACR classification criteria, a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 250 mm or greater, and more than 3 months of chronic knee pain. While patients were excluded for use of topical, oral, or injectable corticosteroids in the month prior to enrollment, they were allowed to continue using analgesics such as NSAIDs if they maintained their daily dose throughout the trial. Mr. Warneke noted the study population was typical of an OA population with a mostly female, mostly Caucasian cohort who had a median age of 60 years and a body mass index of 30 kg/m². Patients had moderate to severe OA and were refractory to previous pain treatments.

The interventions consisted of a single 60-minute application of capsaicin or vehicle to both knees once per day for 4 consecutive days, and patients performed the applications in the clinic. The investigators compared change in WOMAC pain scores between the groups at 31 days, 60 days, and 90 days post dose.

The results at 31 days showed a 46.2% reduction in WOMAC pain scores from baseline for patients using CGS-200-5, compared with a 28.3% reduction in the vehicle group (P = .02). At 60 days, there was a 49.1% reduction in WOMAC pain scores in the CGS-200-5 group, compared with 21.5% in patients using vehicle (P = .0001), and a 42.8% reduction for patients in the CGS-200-5 group at 90 days, compared with 22.8% in the vehicle group (P = .01). The CGS-200-1 group did not reach the primary efficacy WOMAC pain endpoint, compared with vehicle.

A post hoc analysis showed that there was a significantly greater mean reduction in WOMAC total score for patients using CGS-200-5, compared with vehicle at 31 days (P = .02), 60 days (P = .0005), and 90 days post dose (P = .005). “This durability of clinical response for single applications seems to be a promising feature of CGS-200-5,” Mr. Warneke said.

Concerning safety and tolerability, there were no serious adverse events, and one patient discontinued treatment in the CGS-200-5 group. When assessing tolerability at predose, 15-minute, 30-minute, 60-minute, and 90-minute postdose time intervals, the investigators found patients experienced mild or moderate adverse events such as erythema, edema, scaling, and pruritus, with symptoms decreasing by the fourth consecutive day of application.

Mr. Warneke acknowledged the “robust placebo response” in the trial and noted it is not unusual to see in pain studies. “It’s something that is a challenge for all of us who are in this space to overcome, but we still have significant differences here and they are statistically significant as well,” he said. “You have to be pretty good these days to beat the wonder drug placebo, it appears.”

Four authors in addition to Mr. Warneke reported being employees of Vizuri Health Sciences, the company developing CGS-200-5. One author reported being a former consultant for Vizuri. Three authors reported they were current or former employees of CT Clinical Trial & Consulting, a contract research organization employed by Vizuri to execute and manage the study, perform data analysis, and create reports.

SOURCE: Warneke T et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2760.

ATLANTA – Use of high-concentration topical capsaicin was associated with reduced pain, a longer duration of clinical response, and was well tolerated in patients with knee osteoarthritis, compared with lower concentrations of capsaicin and placebo, according to recent research presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

While the ACR has recommended topical capsaicin for the relief of hand and knee OA pain, there are issues with using low-dose capsaicin, including the need for multiple applications and burning, stinging sensations at applications sites. As repeat exposure to capsaicin results in depletion of pain neurotransmitters and a reduction in nerve fibers in a dose-dependent fashion, higher doses of topical capsaicin are a potential topical treatment for OA pain relief, but their tolerability is low, Tim Warneke, vice president of clinical operations at Vizuri Health Sciences in Columbia, Md., said in his presentation.

“[P]oor tolerability has limited the ability to maximize the analgesic effect of capsaicin,” Mr. Warneke said. “While [over-the-counter] preparations of capsaicin provide some pain relief, poor tolerability with higher doses has really left us wondering if we haven’t maximized capsaicin’s ability to provide pain relief.”

Mr. Warneke and colleagues conducted a phase 2, multicenter, double-blind, parallel-group, vehicle-controlled trial where 120 patients with knee OA were randomized in a 1:1:1 ratio to receive 5% capsaicin topical liquid (CGS-200-5), 1% capsaicin topical liquid (CGS-200-1), or vehicle (CGS-200-0) and then followed up to 90 days. “The CGS-200 vehicle was developed to mitigate the burning, stinging pain of capsaicin,” Mr. Warneke said. “It allows the 5% concentration to be well tolerated, which opens the door for increased efficacy, including durability of response.”

Inclusion criteria were radiographically confirmed knee OA using 1986 ACR classification criteria, a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 250 mm or greater, and more than 3 months of chronic knee pain. While patients were excluded for use of topical, oral, or injectable corticosteroids in the month prior to enrollment, they were allowed to continue using analgesics such as NSAIDs if they maintained their daily dose throughout the trial. Mr. Warneke noted the study population was typical of an OA population with a mostly female, mostly Caucasian cohort who had a median age of 60 years and a body mass index of 30 kg/m². Patients had moderate to severe OA and were refractory to previous pain treatments.

The interventions consisted of a single 60-minute application of capsaicin or vehicle to both knees once per day for 4 consecutive days, and patients performed the applications in the clinic. The investigators compared change in WOMAC pain scores between the groups at 31 days, 60 days, and 90 days post dose.

The results at 31 days showed a 46.2% reduction in WOMAC pain scores from baseline for patients using CGS-200-5, compared with a 28.3% reduction in the vehicle group (P = .02). At 60 days, there was a 49.1% reduction in WOMAC pain scores in the CGS-200-5 group, compared with 21.5% in patients using vehicle (P = .0001), and a 42.8% reduction for patients in the CGS-200-5 group at 90 days, compared with 22.8% in the vehicle group (P = .01). The CGS-200-1 group did not reach the primary efficacy WOMAC pain endpoint, compared with vehicle.

A post hoc analysis showed that there was a significantly greater mean reduction in WOMAC total score for patients using CGS-200-5, compared with vehicle at 31 days (P = .02), 60 days (P = .0005), and 90 days post dose (P = .005). “This durability of clinical response for single applications seems to be a promising feature of CGS-200-5,” Mr. Warneke said.

Concerning safety and tolerability, there were no serious adverse events, and one patient discontinued treatment in the CGS-200-5 group. When assessing tolerability at predose, 15-minute, 30-minute, 60-minute, and 90-minute postdose time intervals, the investigators found patients experienced mild or moderate adverse events such as erythema, edema, scaling, and pruritus, with symptoms decreasing by the fourth consecutive day of application.

Mr. Warneke acknowledged the “robust placebo response” in the trial and noted it is not unusual to see in pain studies. “It’s something that is a challenge for all of us who are in this space to overcome, but we still have significant differences here and they are statistically significant as well,” he said. “You have to be pretty good these days to beat the wonder drug placebo, it appears.”

Four authors in addition to Mr. Warneke reported being employees of Vizuri Health Sciences, the company developing CGS-200-5. One author reported being a former consultant for Vizuri. Three authors reported they were current or former employees of CT Clinical Trial & Consulting, a contract research organization employed by Vizuri to execute and manage the study, perform data analysis, and create reports.

SOURCE: Warneke T et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2760.

ATLANTA – Hydroxychloroquine (Plaquenil) 400 mg/day starting by pregnancy week 10 reduces recurrence of congenital heart block in infants born to women with anti-Ro antibodies, according to an open-label, prospective study presented at the annual meeting of the American College of Rheumatology.

M. Alexander Otto/MDedge News

Among antibody-positive women who had a previous pregnancy complicated by congenital heart block (CHB), the regimen reduced recurrence in a subsequent pregnancy from the expected historical rate of 18% to 7.4%, a more than 50% drop. “Given the potential benefit of hydroxychloroquine” (HCQ) and its relative safety during pregnancy, “testing all pregnancies for anti-Ro antibodies, regardless of maternal health, should be considered,” concluded investigators led by rheumatologist Peter Izmirly, MD, associate professor of medicine at New York (N.Y.) University.

About 40% of women with systemic lupus erythematosus and nearly 100% of women with Sjögren’s syndrome, as well as about 1% of women in the general population, have anti-Ro antibodies. They can be present in completely asymptomatic women, which is why the authors called for general screening. Indeed, half of the women in the trial had no or only mild, undifferentiated rheumatic symptoms. Often, “women who carry anti-Ro antibodies have no idea they have them” until they have a child with CHB and are tested, Dr. Izmirly said.

The antibodies cross the placenta and interfere with the normal development of the AV node; about 18% of infants die and most of the rest require lifelong pacing. The risk of CHB in antibody-positive women is about 2%, but once a child is born with the condition, the risk climbs to about 18% in subsequent pregnancies.

Years ago, Dr. Izmirly and his colleagues had a hunch that HCQ might help because it disrupts the toll-like receptor signaling involved in the disease process. A database review he led added weight to the idea, finding that among 257 anti-Ro positive pregnancies, the rate of CHB was 7.5% among the 40 women who happened to take HCQ, versus 21.2% among the 217 who did not. “We wanted to see if we could replicate that prospectively,” he said.

The Preventive Approach to Congenital Heart Block with Hydroxychloroquine (PATCH) trial enrolled 54 antibody positive women with a previous CHB pregnancy. They were started on 400 mg/day HCQ by gestation week 10.

There were four cases of second- or third-degree CHB among the women (7.4%, P = 0.02), all detected by fetal echocardiogram around week 20.

Nine of the women were treated with IVIG and/or dexamethasone for lupus flares or fetal heart issues other than advanced block, which confounded the results. To analyze the effect in a purely HCQ cohort, the team recruited an additional nine women not treated with any other medication during pregnancy, one of whose fetus developed third-degree heart block.

In total, 5 of 63 pregnancies (7.9%) resulted in advanced block. Among the 54 women exposed only to HCQ, the rate of second- or third-degree block was again 7.4% (4 of 54, P = .02). HCQ compliance, assessed by maternal blood levels above 200 ng/mL at least once, was 98%, and cord blood confirmed fetal exposure to HCQ.

Once detected, CHB was treated with dexamethasone or IVIG. One case progressed to cardiomyopathy, and the pregnancy was terminated. Another child required pacing after birth. Other children reverted to normal sinus rhythm but had intermittent second-degree block at age 2.

Overall, “the safety in this study was excellent,” said rheumatologist and senior investigator Jill Buyon, MD, director of the division of rheumatology at New York University.

The complications – nine births before 37 weeks, one infant small for gestational age – were not unexpected in a rheumatic population. “We were very nervous about Plaquenil cardiomyopathy” in the pregnancy that was terminated, but there was no evidence of it on histology.

The children will have ocular optical coherence tomography at age 5 to check for retinal toxicity; the 12 who have been tested so far show no obvious signs. Dr. Izmirly said he doesn’t expect to see any problems. “We are just being super cautious.”

The audience had questions about why the trial didn’t have a placebo arm. He explained that CHB is a rare event – one in 15,000 pregnancies – and it took 8 years just to adequately power the single-arm study; recruiting more than 100 additional women for a placebo-controlled trial wasn’t practical.

Also, “there was no way” women were going to be randomized to placebo when HCQ seemed so promising; 35% of the enrollees had already lost a child to CHB. “Everyone wanted the drug,” Dr. Izmirly said.

The majority of women were white, and about half met criteria for lupus and/or Sjögren’s. Anti-Ro levels remained above 1,000 EU throughout pregnancy. Women were excluded if they were taking high-dose prednisone or any dose of fluorinated corticosteroids at baseline.

The National Institutes of Health funded the work. The investigators had no relevant disclosures.

[email protected]

SOURCE: Izmirly P et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1761.

ATLANTA – Hydroxychloroquine (Plaquenil) 400 mg/day starting by pregnancy week 10 reduces recurrence of congenital heart block in infants born to women with anti-Ro antibodies, according to an open-label, prospective study presented at the annual meeting of the American College of Rheumatology.

M. Alexander Otto/MDedge News

Among antibody-positive women who had a previous pregnancy complicated by congenital heart block (CHB), the regimen reduced recurrence in a subsequent pregnancy from the expected historical rate of 18% to 7.4%, a more than 50% drop. “Given the potential benefit of hydroxychloroquine” (HCQ) and its relative safety during pregnancy, “testing all pregnancies for anti-Ro antibodies, regardless of maternal health, should be considered,” concluded investigators led by rheumatologist Peter Izmirly, MD, associate professor of medicine at New York (N.Y.) University.

About 40% of women with systemic lupus erythematosus and nearly 100% of women with Sjögren’s syndrome, as well as about 1% of women in the general population, have anti-Ro antibodies. They can be present in completely asymptomatic women, which is why the authors called for general screening. Indeed, half of the women in the trial had no or only mild, undifferentiated rheumatic symptoms. Often, “women who carry anti-Ro antibodies have no idea they have them” until they have a child with CHB and are tested, Dr. Izmirly said.

The antibodies cross the placenta and interfere with the normal development of the AV node; about 18% of infants die and most of the rest require lifelong pacing. The risk of CHB in antibody-positive women is about 2%, but once a child is born with the condition, the risk climbs to about 18% in subsequent pregnancies.

Years ago, Dr. Izmirly and his colleagues had a hunch that HCQ might help because it disrupts the toll-like receptor signaling involved in the disease process. A database review he led added weight to the idea, finding that among 257 anti-Ro positive pregnancies, the rate of CHB was 7.5% among the 40 women who happened to take HCQ, versus 21.2% among the 217 who did not. “We wanted to see if we could replicate that prospectively,” he said.

The Preventive Approach to Congenital Heart Block with Hydroxychloroquine (PATCH) trial enrolled 54 antibody positive women with a previous CHB pregnancy. They were started on 400 mg/day HCQ by gestation week 10.

There were four cases of second- or third-degree CHB among the women (7.4%, P = 0.02), all detected by fetal echocardiogram around week 20.

Nine of the women were treated with IVIG and/or dexamethasone for lupus flares or fetal heart issues other than advanced block, which confounded the results. To analyze the effect in a purely HCQ cohort, the team recruited an additional nine women not treated with any other medication during pregnancy, one of whose fetus developed third-degree heart block.

In total, 5 of 63 pregnancies (7.9%) resulted in advanced block. Among the 54 women exposed only to HCQ, the rate of second- or third-degree block was again 7.4% (4 of 54, P = .02). HCQ compliance, assessed by maternal blood levels above 200 ng/mL at least once, was 98%, and cord blood confirmed fetal exposure to HCQ.

Once detected, CHB was treated with dexamethasone or IVIG. One case progressed to cardiomyopathy, and the pregnancy was terminated. Another child required pacing after birth. Other children reverted to normal sinus rhythm but had intermittent second-degree block at age 2.

Overall, “the safety in this study was excellent,” said rheumatologist and senior investigator Jill Buyon, MD, director of the division of rheumatology at New York University.

The complications – nine births before 37 weeks, one infant small for gestational age – were not unexpected in a rheumatic population. “We were very nervous about Plaquenil cardiomyopathy” in the pregnancy that was terminated, but there was no evidence of it on histology.

The children will have ocular optical coherence tomography at age 5 to check for retinal toxicity; the 12 who have been tested so far show no obvious signs. Dr. Izmirly said he doesn’t expect to see any problems. “We are just being super cautious.”

The audience had questions about why the trial didn’t have a placebo arm. He explained that CHB is a rare event – one in 15,000 pregnancies – and it took 8 years just to adequately power the single-arm study; recruiting more than 100 additional women for a placebo-controlled trial wasn’t practical.

Also, “there was no way” women were going to be randomized to placebo when HCQ seemed so promising; 35% of the enrollees had already lost a child to CHB. “Everyone wanted the drug,” Dr. Izmirly said.

The majority of women were white, and about half met criteria for lupus and/or Sjögren’s. Anti-Ro levels remained above 1,000 EU throughout pregnancy. Women were excluded if they were taking high-dose prednisone or any dose of fluorinated corticosteroids at baseline.

The National Institutes of Health funded the work. The investigators had no relevant disclosures.

[email protected]

SOURCE: Izmirly P et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1761.

ATLANTA – Hydroxychloroquine (Plaquenil) 400 mg/day starting by pregnancy week 10 reduces recurrence of congenital heart block in infants born to women with anti-Ro antibodies, according to an open-label, prospective study presented at the annual meeting of the American College of Rheumatology.

M. Alexander Otto/MDedge News

Among antibody-positive women who had a previous pregnancy complicated by congenital heart block (CHB), the regimen reduced recurrence in a subsequent pregnancy from the expected historical rate of 18% to 7.4%, a more than 50% drop. “Given the potential benefit of hydroxychloroquine” (HCQ) and its relative safety during pregnancy, “testing all pregnancies for anti-Ro antibodies, regardless of maternal health, should be considered,” concluded investigators led by rheumatologist Peter Izmirly, MD, associate professor of medicine at New York (N.Y.) University.

About 40% of women with systemic lupus erythematosus and nearly 100% of women with Sjögren’s syndrome, as well as about 1% of women in the general population, have anti-Ro antibodies. They can be present in completely asymptomatic women, which is why the authors called for general screening. Indeed, half of the women in the trial had no or only mild, undifferentiated rheumatic symptoms. Often, “women who carry anti-Ro antibodies have no idea they have them” until they have a child with CHB and are tested, Dr. Izmirly said.

The antibodies cross the placenta and interfere with the normal development of the AV node; about 18% of infants die and most of the rest require lifelong pacing. The risk of CHB in antibody-positive women is about 2%, but once a child is born with the condition, the risk climbs to about 18% in subsequent pregnancies.

Years ago, Dr. Izmirly and his colleagues had a hunch that HCQ might help because it disrupts the toll-like receptor signaling involved in the disease process. A database review he led added weight to the idea, finding that among 257 anti-Ro positive pregnancies, the rate of CHB was 7.5% among the 40 women who happened to take HCQ, versus 21.2% among the 217 who did not. “We wanted to see if we could replicate that prospectively,” he said.

The Preventive Approach to Congenital Heart Block with Hydroxychloroquine (PATCH) trial enrolled 54 antibody positive women with a previous CHB pregnancy. They were started on 400 mg/day HCQ by gestation week 10.

There were four cases of second- or third-degree CHB among the women (7.4%, P = 0.02), all detected by fetal echocardiogram around week 20.

Nine of the women were treated with IVIG and/or dexamethasone for lupus flares or fetal heart issues other than advanced block, which confounded the results. To analyze the effect in a purely HCQ cohort, the team recruited an additional nine women not treated with any other medication during pregnancy, one of whose fetus developed third-degree heart block.

In total, 5 of 63 pregnancies (7.9%) resulted in advanced block. Among the 54 women exposed only to HCQ, the rate of second- or third-degree block was again 7.4% (4 of 54, P = .02). HCQ compliance, assessed by maternal blood levels above 200 ng/mL at least once, was 98%, and cord blood confirmed fetal exposure to HCQ.

Once detected, CHB was treated with dexamethasone or IVIG. One case progressed to cardiomyopathy, and the pregnancy was terminated. Another child required pacing after birth. Other children reverted to normal sinus rhythm but had intermittent second-degree block at age 2.

Overall, “the safety in this study was excellent,” said rheumatologist and senior investigator Jill Buyon, MD, director of the division of rheumatology at New York University.

The complications – nine births before 37 weeks, one infant small for gestational age – were not unexpected in a rheumatic population. “We were very nervous about Plaquenil cardiomyopathy” in the pregnancy that was terminated, but there was no evidence of it on histology.

The children will have ocular optical coherence tomography at age 5 to check for retinal toxicity; the 12 who have been tested so far show no obvious signs. Dr. Izmirly said he doesn’t expect to see any problems. “We are just being super cautious.”

The audience had questions about why the trial didn’t have a placebo arm. He explained that CHB is a rare event – one in 15,000 pregnancies – and it took 8 years just to adequately power the single-arm study; recruiting more than 100 additional women for a placebo-controlled trial wasn’t practical.

Also, “there was no way” women were going to be randomized to placebo when HCQ seemed so promising; 35% of the enrollees had already lost a child to CHB. “Everyone wanted the drug,” Dr. Izmirly said.

The majority of women were white, and about half met criteria for lupus and/or Sjögren’s. Anti-Ro levels remained above 1,000 EU throughout pregnancy. Women were excluded if they were taking high-dose prednisone or any dose of fluorinated corticosteroids at baseline.

The National Institutes of Health funded the work. The investigators had no relevant disclosures.

[email protected]

SOURCE: Izmirly P et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1761.

The American College of Rheumatology and the European League Against Rheumatism have released the first classification criteria for IgG4-related disease.

Although it was first recognized as a distinct disease in 2003, investigators have since learned that IgG4-related disease (IgG4-RD) is not particularly rare. Specialists across many different fields of medicine now treat IgG4-RD, which affects multiple organ systems, and the pancreas, kidneys, and orbits are most commonly affected by severe disease.

“IgG4-RD has proven to be a remarkable window into human immunology, and the insights investigators have made from studying this disease have already led to important discoveries in other rheumatic diseases, such as scleroderma,” John H. Stone, MD, professor of medicine at Harvard Medical School and director of clinical rheumatology at Massachusetts General Hospital, both in Boston, said in an interview.

To develop the classification criteria, 86 experts from five continents across various subspecialties including rheumatology, internal medicine, ophthalmology, pathology, gastroenterology, allergology, pulmonology, radiology, neurology, nephrology, and others met as a working group in 2016, achieving consensus on 79 criteria. They then narrowed down the number of items to 8 domains and 29 items within a set of inclusion and exclusion criteria for the draft classification criteria. For the final classification criteria, the working group applied weighting to each inclusion criteria item within a domain on a Likert scale (–5 to 5 range), removing items that were not significantly attributable to IgG4-RD classification (those with –2 to 2 scores).

The final IgG4-RD criteria are divided into three classification steps: entry criteria, exclusion criteria, and inclusion criteria. Patients who meet the entry criteria should have clinical or radiologic involvement of one or more organs consistent with IgG4-RD, such as the pancreas, salivary glands, bile ducts, orbits, kidney, lung, aorta, retroperitoneum, pachymeninges, or thyroid gland. Patients could alternatively meet the entry criteria by having “pathologic evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain etiology in one of these same organs,” the authors wrote.

If a patient meets the entry criteria, their case is examined against 32 clinical, serologic, radiologic, and pathologic items and specific disease inclusions. Any exclusion criteria present in a case means the patient does not meet the criteria for IgG4-RD classification.

The third step is to evaluate whether a patient meets inclusion criteria consisting of clinical findings, serologic results, radiology assessments, and pathology interpretations across eight domains: immunostaining, head and neck gland involvement, chest, pancreas and biliary tree, kidney, and the retroperitoneum. Each criterion has a weight, and if a patient has a score of 20 or higher, they meet the classification criteria for IgG4-RD.

“The final criteria set is easy to use and lends itself well to adaptation in an electronic format, which we have already instituted at my hospital,” said Dr. Stone, who is also director of the international panel of experts who created the criteria.

Two cohorts were used to validate the IgG4-RD classification criteria. In the first cohort, investigators used 771 patients (85% of the total cohort) in whom they were “confident” or “very confident” of a diagnosis of IgG4-RD or a mimicker to assess the test performance with a classification threshold of 20 points. The researchers found the criteria had a specificity of 99.2% (95% confidence interval, 97.2%-99.8%) and a sensitivity of 85.5% (95% CI, 81.9%-88.5%). The experts used a second validation cohort of 402 additional patients (83% of the total cohort) with suspected IgG4-RD or a mimicker using the same confident and very confident metric. The panel assembled this cohort because of minor definition changes in inclusion and exclusion criteria that had been made after the derivation set of patients had been collected, but the definitions of inclusion and exclusion criteria used in the two validation cohorts were exactly the same. Overall, the specificity of the criteria was 97.8% (95% CI, 93.7%-99.2%) and the sensitivity was 82.0% (95% CI, 77.0%-86.1%) for IgG4-RD classification in this second group.

Dr. Stone said that more investigations, including multicenter clinical trials, are being organized for patients with IgG4-RD, and these classification criteria will help to identify which patients to include in these studies.

“These rigorous ACR/EULAR classification criteria will help guide us through some of the most important challenges of studying this disease well,” Dr. Stone said. “I’m anticipating major advances in this field in the years to come, triggered in part by the strength of having sound classification criteria.”

The authors reported no relevant conflicts of interest.

SOURCE: Wallace ZS et al. Arthritis Rheumatol. 2019 Dec 2. doi: 10.1002/art.41120.

The American College of Rheumatology and the European League Against Rheumatism have released the first classification criteria for IgG4-related disease.

Although it was first recognized as a distinct disease in 2003, investigators have since learned that IgG4-related disease (IgG4-RD) is not particularly rare. Specialists across many different fields of medicine now treat IgG4-RD, which affects multiple organ systems, and the pancreas, kidneys, and orbits are most commonly affected by severe disease.

“IgG4-RD has proven to be a remarkable window into human immunology, and the insights investigators have made from studying this disease have already led to important discoveries in other rheumatic diseases, such as scleroderma,” John H. Stone, MD, professor of medicine at Harvard Medical School and director of clinical rheumatology at Massachusetts General Hospital, both in Boston, said in an interview.

To develop the classification criteria, 86 experts from five continents across various subspecialties including rheumatology, internal medicine, ophthalmology, pathology, gastroenterology, allergology, pulmonology, radiology, neurology, nephrology, and others met as a working group in 2016, achieving consensus on 79 criteria. They then narrowed down the number of items to 8 domains and 29 items within a set of inclusion and exclusion criteria for the draft classification criteria. For the final classification criteria, the working group applied weighting to each inclusion criteria item within a domain on a Likert scale (–5 to 5 range), removing items that were not significantly attributable to IgG4-RD classification (those with –2 to 2 scores).

The final IgG4-RD criteria are divided into three classification steps: entry criteria, exclusion criteria, and inclusion criteria. Patients who meet the entry criteria should have clinical or radiologic involvement of one or more organs consistent with IgG4-RD, such as the pancreas, salivary glands, bile ducts, orbits, kidney, lung, aorta, retroperitoneum, pachymeninges, or thyroid gland. Patients could alternatively meet the entry criteria by having “pathologic evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain etiology in one of these same organs,” the authors wrote.

If a patient meets the entry criteria, their case is examined against 32 clinical, serologic, radiologic, and pathologic items and specific disease inclusions. Any exclusion criteria present in a case means the patient does not meet the criteria for IgG4-RD classification.

The third step is to evaluate whether a patient meets inclusion criteria consisting of clinical findings, serologic results, radiology assessments, and pathology interpretations across eight domains: immunostaining, head and neck gland involvement, chest, pancreas and biliary tree, kidney, and the retroperitoneum. Each criterion has a weight, and if a patient has a score of 20 or higher, they meet the classification criteria for IgG4-RD.

“The final criteria set is easy to use and lends itself well to adaptation in an electronic format, which we have already instituted at my hospital,” said Dr. Stone, who is also director of the international panel of experts who created the criteria.

Two cohorts were used to validate the IgG4-RD classification criteria. In the first cohort, investigators used 771 patients (85% of the total cohort) in whom they were “confident” or “very confident” of a diagnosis of IgG4-RD or a mimicker to assess the test performance with a classification threshold of 20 points. The researchers found the criteria had a specificity of 99.2% (95% confidence interval, 97.2%-99.8%) and a sensitivity of 85.5% (95% CI, 81.9%-88.5%). The experts used a second validation cohort of 402 additional patients (83% of the total cohort) with suspected IgG4-RD or a mimicker using the same confident and very confident metric. The panel assembled this cohort because of minor definition changes in inclusion and exclusion criteria that had been made after the derivation set of patients had been collected, but the definitions of inclusion and exclusion criteria used in the two validation cohorts were exactly the same. Overall, the specificity of the criteria was 97.8% (95% CI, 93.7%-99.2%) and the sensitivity was 82.0% (95% CI, 77.0%-86.1%) for IgG4-RD classification in this second group.

Dr. Stone said that more investigations, including multicenter clinical trials, are being organized for patients with IgG4-RD, and these classification criteria will help to identify which patients to include in these studies.

“These rigorous ACR/EULAR classification criteria will help guide us through some of the most important challenges of studying this disease well,” Dr. Stone said. “I’m anticipating major advances in this field in the years to come, triggered in part by the strength of having sound classification criteria.”

The authors reported no relevant conflicts of interest.

SOURCE: Wallace ZS et al. Arthritis Rheumatol. 2019 Dec 2. doi: 10.1002/art.41120.

The American College of Rheumatology and the European League Against Rheumatism have released the first classification criteria for IgG4-related disease.

Although it was first recognized as a distinct disease in 2003, investigators have since learned that IgG4-related disease (IgG4-RD) is not particularly rare. Specialists across many different fields of medicine now treat IgG4-RD, which affects multiple organ systems, and the pancreas, kidneys, and orbits are most commonly affected by severe disease.

“IgG4-RD has proven to be a remarkable window into human immunology, and the insights investigators have made from studying this disease have already led to important discoveries in other rheumatic diseases, such as scleroderma,” John H. Stone, MD, professor of medicine at Harvard Medical School and director of clinical rheumatology at Massachusetts General Hospital, both in Boston, said in an interview.

To develop the classification criteria, 86 experts from five continents across various subspecialties including rheumatology, internal medicine, ophthalmology, pathology, gastroenterology, allergology, pulmonology, radiology, neurology, nephrology, and others met as a working group in 2016, achieving consensus on 79 criteria. They then narrowed down the number of items to 8 domains and 29 items within a set of inclusion and exclusion criteria for the draft classification criteria. For the final classification criteria, the working group applied weighting to each inclusion criteria item within a domain on a Likert scale (–5 to 5 range), removing items that were not significantly attributable to IgG4-RD classification (those with –2 to 2 scores).

The final IgG4-RD criteria are divided into three classification steps: entry criteria, exclusion criteria, and inclusion criteria. Patients who meet the entry criteria should have clinical or radiologic involvement of one or more organs consistent with IgG4-RD, such as the pancreas, salivary glands, bile ducts, orbits, kidney, lung, aorta, retroperitoneum, pachymeninges, or thyroid gland. Patients could alternatively meet the entry criteria by having “pathologic evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain etiology in one of these same organs,” the authors wrote.

If a patient meets the entry criteria, their case is examined against 32 clinical, serologic, radiologic, and pathologic items and specific disease inclusions. Any exclusion criteria present in a case means the patient does not meet the criteria for IgG4-RD classification.

The third step is to evaluate whether a patient meets inclusion criteria consisting of clinical findings, serologic results, radiology assessments, and pathology interpretations across eight domains: immunostaining, head and neck gland involvement, chest, pancreas and biliary tree, kidney, and the retroperitoneum. Each criterion has a weight, and if a patient has a score of 20 or higher, they meet the classification criteria for IgG4-RD.

“The final criteria set is easy to use and lends itself well to adaptation in an electronic format, which we have already instituted at my hospital,” said Dr. Stone, who is also director of the international panel of experts who created the criteria.

Two cohorts were used to validate the IgG4-RD classification criteria. In the first cohort, investigators used 771 patients (85% of the total cohort) in whom they were “confident” or “very confident” of a diagnosis of IgG4-RD or a mimicker to assess the test performance with a classification threshold of 20 points. The researchers found the criteria had a specificity of 99.2% (95% confidence interval, 97.2%-99.8%) and a sensitivity of 85.5% (95% CI, 81.9%-88.5%). The experts used a second validation cohort of 402 additional patients (83% of the total cohort) with suspected IgG4-RD or a mimicker using the same confident and very confident metric. The panel assembled this cohort because of minor definition changes in inclusion and exclusion criteria that had been made after the derivation set of patients had been collected, but the definitions of inclusion and exclusion criteria used in the two validation cohorts were exactly the same. Overall, the specificity of the criteria was 97.8% (95% CI, 93.7%-99.2%) and the sensitivity was 82.0% (95% CI, 77.0%-86.1%) for IgG4-RD classification in this second group.

Dr. Stone said that more investigations, including multicenter clinical trials, are being organized for patients with IgG4-RD, and these classification criteria will help to identify which patients to include in these studies.

“These rigorous ACR/EULAR classification criteria will help guide us through some of the most important challenges of studying this disease well,” Dr. Stone said. “I’m anticipating major advances in this field in the years to come, triggered in part by the strength of having sound classification criteria.”

The authors reported no relevant conflicts of interest.

SOURCE: Wallace ZS et al. Arthritis Rheumatol. 2019 Dec 2. doi: 10.1002/art.41120.

The length of time a patient with rheumatoid arthritis takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

“Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow,” the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings “show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage,” they continue.

Mark Tatangelo of the University of Toronto and colleagues published their findings online Dec. 6, 2019, in JAMA Network Open.

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the clinical epidemiology program at Massachusetts General Hospital in Boston, writes: “A distinctive feature of the report by Tatangelo et al. was the emphasis on longer time to initiation of biologic therapy as an ideal outcome.”

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

Dr. McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that “peer effects” influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. “While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important,” Dr. McCormick writes.

The variation in highest biologic DMARD use, compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

“A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors,” the authors write. “For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (U.S. $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [U.S. $11,460]).”

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million).

Dr. McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study “may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events.”

Dr. McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. “[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD,” the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

Dr. McCormick reports a fellowship award from the Canadian Institutes of Health Research.

SOURCES: Tatangelo M et al. JAMA Netw Open. 2019;2(12):e1917053. doi: 10.1001/jamanetworkopen.2019.17053; McCormick N. JAMA Netw Open. 2019;2(12):e1917065. doi: 10.1001/jamanetworkopen.2019.17065

This story first appeared on Medscape.com.

The length of time a patient with rheumatoid arthritis takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

“Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow,” the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings “show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage,” they continue.

Mark Tatangelo of the University of Toronto and colleagues published their findings online Dec. 6, 2019, in JAMA Network Open.

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the clinical epidemiology program at Massachusetts General Hospital in Boston, writes: “A distinctive feature of the report by Tatangelo et al. was the emphasis on longer time to initiation of biologic therapy as an ideal outcome.”

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

Dr. McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that “peer effects” influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. “While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important,” Dr. McCormick writes.

The variation in highest biologic DMARD use, compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

“A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors,” the authors write. “For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (U.S. $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [U.S. $11,460]).”

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million).

Dr. McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study “may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events.”

Dr. McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. “[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD,” the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

Dr. McCormick reports a fellowship award from the Canadian Institutes of Health Research.

SOURCES: Tatangelo M et al. JAMA Netw Open. 2019;2(12):e1917053. doi: 10.1001/jamanetworkopen.2019.17053; McCormick N. JAMA Netw Open. 2019;2(12):e1917065. doi: 10.1001/jamanetworkopen.2019.17065

This story first appeared on Medscape.com.

The length of time a patient with rheumatoid arthritis takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

“Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow,” the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings “show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage,” they continue.

Mark Tatangelo of the University of Toronto and colleagues published their findings online Dec. 6, 2019, in JAMA Network Open.

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the clinical epidemiology program at Massachusetts General Hospital in Boston, writes: “A distinctive feature of the report by Tatangelo et al. was the emphasis on longer time to initiation of biologic therapy as an ideal outcome.”

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

Dr. McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that “peer effects” influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. “While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important,” Dr. McCormick writes.

The variation in highest biologic DMARD use, compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

“A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors,” the authors write. “For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (U.S. $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [U.S. $11,460]).”

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million).

Dr. McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study “may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events.”

Dr. McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. “[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD,” the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

Dr. McCormick reports a fellowship award from the Canadian Institutes of Health Research.

SOURCES: Tatangelo M et al. JAMA Netw Open. 2019;2(12):e1917053. doi: 10.1001/jamanetworkopen.2019.17053; McCormick N. JAMA Netw Open. 2019;2(12):e1917065. doi: 10.1001/jamanetworkopen.2019.17065

This story first appeared on Medscape.com.

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.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Soon-to-be-published gout guidelines from the American College of Rheumatology will recommend dosing allopurinol above 300 mg/day to get serum urate below 6 mg/dL, even in people with renal impairment.

M. Alexander Otto/MDedge News

It’s the same strong treat-to-target recommendation the group made in its last outing in 2012, but “we now have more evidence to support it,” said co–lead author, rheumatologist, and epidemiologist Tuhina Neogi, MD, PhD, a professor of medicine at Boston University.

She gave a sneak preview of the new guidelines, which will be published in 2020, at the ACR annual meeting. They are under review, but she said the “major recommendations will remain the same.”

“There will still be controversy that we have not yet proven that a threshold of 6 mg/dL is better than a threshold of 7 mg/dL, but we know that” at physiologic pH and temperature, monosodium urate starts to crystallize out at 6.8 mg/dL. “Serum urate is not a perfect measure or total body urate, so we need to get urate to below at least 6 mg/dL,” she said, and perhaps lower in some.

A popular alternative in primary care – where most gout is managed – is to treat to avoid symptoms. It “has no evidence,” and people “end up getting tophaceous gout with joint destruction. Suppressive colchicine therapy does not manage underlying hyperuricemia,” Dr. Neogi said.

With the symptom approach, “patients are often [profoundly] dismayed” when they find out they have large tophi and joint damage because they weren’t managed properly. “Primary care physicians [don’t often] see that because those patients don’t go back to them,” she said.

Dr. Neogi suspects that, for rheumatologists, the biggest surprise in the new guidelines will be a deemphasis on lifestyle and dietary factors. They can be triggers, but “gout is increasingly recognized as largely genetically determined,” and the impact of other factors on serum urate is low. Plus, “patients are embarrassed” by gout, and even less comfortable being honest with physicians “if they think we are blaming them,” she said.

The new document will recommend allopurinol as the definitive first-line option for hyperuricemia. Febuxostat (Uloric) was put on pretty much equal footing in 2012, but now “we acknowledge” that allopurinol dosing in head-to-head trials – 300 mg/day or 200 mg/day with renal impairment – was too low for most people, “so to say febuxostat is equivalent or superior isn’t really fair.” The substantially higher cost of febuxostat was also taken into consideration, she said.

The ACR will broaden the indications for urate lowering beyond frequent flares, tophi, and radiologic joint damage to include conditional, shared decision-making recommendations for people who have less than two flares per year, those with kidney stones, and people with a first flare if they are particularly susceptible to a second – namely those with serum urate at or above 9 mg/dL and people with stage 3 or worse chronic kidney disease, who are less able to tolerate NSAIDs and colchicine for symptom treatment.

The group will also relax its advice against treating asymptomatic hyperuricemia. Febuxostat trials have shown a reduction in incident gout, but the number needed to treat was large, so the ACR will recommend shared decision making.

Inadequate allopurinol dosing, meanwhile, has been the bête noire of rheumatology for years, but there is still reluctance among many to go above 300 mg/day. Dr. Neogi said it’s because of a decades-old concern, “unsupported by any evidence, that higher doses may be detrimental in people with renal insufficiency.” It’s frustrating, she said, because “there is good data supporting the safety of increasing the dose above 300 mg/day even in those with renal impairment,” and not doing so opens the door to entirely preventable complications.

As for allopurinol hypersensitivity – another reason people shy away from higher dosing, especially in the renally impaired – the trick is to start low and slowly titrate allopurinol up to the target urate range. Asian and black people, especially, should be screened beforehand for the HLA-B*58:01 genetic variant that increases the risk of severe reactions. Both will be strong recommendations in the new guidelines.

Dr. Neogi didn’t have any relevant industry disclosures.

[email protected]

ATLANTA – Soon-to-be-published gout guidelines from the American College of Rheumatology will recommend dosing allopurinol above 300 mg/day to get serum urate below 6 mg/dL, even in people with renal impairment.

M. Alexander Otto/MDedge News

It’s the same strong treat-to-target recommendation the group made in its last outing in 2012, but “we now have more evidence to support it,” said co–lead author, rheumatologist, and epidemiologist Tuhina Neogi, MD, PhD, a professor of medicine at Boston University.

She gave a sneak preview of the new guidelines, which will be published in 2020, at the ACR annual meeting. They are under review, but she said the “major recommendations will remain the same.”

“There will still be controversy that we have not yet proven that a threshold of 6 mg/dL is better than a threshold of 7 mg/dL, but we know that” at physiologic pH and temperature, monosodium urate starts to crystallize out at 6.8 mg/dL. “Serum urate is not a perfect measure or total body urate, so we need to get urate to below at least 6 mg/dL,” she said, and perhaps lower in some.

A popular alternative in primary care – where most gout is managed – is to treat to avoid symptoms. It “has no evidence,” and people “end up getting tophaceous gout with joint destruction. Suppressive colchicine therapy does not manage underlying hyperuricemia,” Dr. Neogi said.

With the symptom approach, “patients are often [profoundly] dismayed” when they find out they have large tophi and joint damage because they weren’t managed properly. “Primary care physicians [don’t often] see that because those patients don’t go back to them,” she said.

Dr. Neogi suspects that, for rheumatologists, the biggest surprise in the new guidelines will be a deemphasis on lifestyle and dietary factors. They can be triggers, but “gout is increasingly recognized as largely genetically determined,” and the impact of other factors on serum urate is low. Plus, “patients are embarrassed” by gout, and even less comfortable being honest with physicians “if they think we are blaming them,” she said.

The new document will recommend allopurinol as the definitive first-line option for hyperuricemia. Febuxostat (Uloric) was put on pretty much equal footing in 2012, but now “we acknowledge” that allopurinol dosing in head-to-head trials – 300 mg/day or 200 mg/day with renal impairment – was too low for most people, “so to say febuxostat is equivalent or superior isn’t really fair.” The substantially higher cost of febuxostat was also taken into consideration, she said.

The ACR will broaden the indications for urate lowering beyond frequent flares, tophi, and radiologic joint damage to include conditional, shared decision-making recommendations for people who have less than two flares per year, those with kidney stones, and people with a first flare if they are particularly susceptible to a second – namely those with serum urate at or above 9 mg/dL and people with stage 3 or worse chronic kidney disease, who are less able to tolerate NSAIDs and colchicine for symptom treatment.

The group will also relax its advice against treating asymptomatic hyperuricemia. Febuxostat trials have shown a reduction in incident gout, but the number needed to treat was large, so the ACR will recommend shared decision making.

Inadequate allopurinol dosing, meanwhile, has been the bête noire of rheumatology for years, but there is still reluctance among many to go above 300 mg/day. Dr. Neogi said it’s because of a decades-old concern, “unsupported by any evidence, that higher doses may be detrimental in people with renal insufficiency.” It’s frustrating, she said, because “there is good data supporting the safety of increasing the dose above 300 mg/day even in those with renal impairment,” and not doing so opens the door to entirely preventable complications.

As for allopurinol hypersensitivity – another reason people shy away from higher dosing, especially in the renally impaired – the trick is to start low and slowly titrate allopurinol up to the target urate range. Asian and black people, especially, should be screened beforehand for the HLA-B*58:01 genetic variant that increases the risk of severe reactions. Both will be strong recommendations in the new guidelines.

Dr. Neogi didn’t have any relevant industry disclosures.

[email protected]

ATLANTA – Soon-to-be-published gout guidelines from the American College of Rheumatology will recommend dosing allopurinol above 300 mg/day to get serum urate below 6 mg/dL, even in people with renal impairment.

M. Alexander Otto/MDedge News

It’s the same strong treat-to-target recommendation the group made in its last outing in 2012, but “we now have more evidence to support it,” said co–lead author, rheumatologist, and epidemiologist Tuhina Neogi, MD, PhD, a professor of medicine at Boston University.

She gave a sneak preview of the new guidelines, which will be published in 2020, at the ACR annual meeting. They are under review, but she said the “major recommendations will remain the same.”

“There will still be controversy that we have not yet proven that a threshold of 6 mg/dL is better than a threshold of 7 mg/dL, but we know that” at physiologic pH and temperature, monosodium urate starts to crystallize out at 6.8 mg/dL. “Serum urate is not a perfect measure or total body urate, so we need to get urate to below at least 6 mg/dL,” she said, and perhaps lower in some.

A popular alternative in primary care – where most gout is managed – is to treat to avoid symptoms. It “has no evidence,” and people “end up getting tophaceous gout with joint destruction. Suppressive colchicine therapy does not manage underlying hyperuricemia,” Dr. Neogi said.

With the symptom approach, “patients are often [profoundly] dismayed” when they find out they have large tophi and joint damage because they weren’t managed properly. “Primary care physicians [don’t often] see that because those patients don’t go back to them,” she said.

Dr. Neogi suspects that, for rheumatologists, the biggest surprise in the new guidelines will be a deemphasis on lifestyle and dietary factors. They can be triggers, but “gout is increasingly recognized as largely genetically determined,” and the impact of other factors on serum urate is low. Plus, “patients are embarrassed” by gout, and even less comfortable being honest with physicians “if they think we are blaming them,” she said.

The new document will recommend allopurinol as the definitive first-line option for hyperuricemia. Febuxostat (Uloric) was put on pretty much equal footing in 2012, but now “we acknowledge” that allopurinol dosing in head-to-head trials – 300 mg/day or 200 mg/day with renal impairment – was too low for most people, “so to say febuxostat is equivalent or superior isn’t really fair.” The substantially higher cost of febuxostat was also taken into consideration, she said.

The ACR will broaden the indications for urate lowering beyond frequent flares, tophi, and radiologic joint damage to include conditional, shared decision-making recommendations for people who have less than two flares per year, those with kidney stones, and people with a first flare if they are particularly susceptible to a second – namely those with serum urate at or above 9 mg/dL and people with stage 3 or worse chronic kidney disease, who are less able to tolerate NSAIDs and colchicine for symptom treatment.

The group will also relax its advice against treating asymptomatic hyperuricemia. Febuxostat trials have shown a reduction in incident gout, but the number needed to treat was large, so the ACR will recommend shared decision making.

Inadequate allopurinol dosing, meanwhile, has been the bête noire of rheumatology for years, but there is still reluctance among many to go above 300 mg/day. Dr. Neogi said it’s because of a decades-old concern, “unsupported by any evidence, that higher doses may be detrimental in people with renal insufficiency.” It’s frustrating, she said, because “there is good data supporting the safety of increasing the dose above 300 mg/day even in those with renal impairment,” and not doing so opens the door to entirely preventable complications.

As for allopurinol hypersensitivity – another reason people shy away from higher dosing, especially in the renally impaired – the trick is to start low and slowly titrate allopurinol up to the target urate range. Asian and black people, especially, should be screened beforehand for the HLA-B*58:01 genetic variant that increases the risk of severe reactions. Both will be strong recommendations in the new guidelines.

Dr. Neogi didn’t have any relevant industry disclosures.

[email protected]