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First validated classification criteria for discoid lupus erythematosus unveiled
The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.
“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”
Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”
In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.
At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.
A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.
The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).
When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).
“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”
For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.
According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.
Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”
Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.
Dr. Elman reported having no financial disclosures.
The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.
“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”
Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”
In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.
At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.
A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.
The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).
When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).
“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”
For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.
According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.
Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”
Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.
Dr. Elman reported having no financial disclosures.
The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.
“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”
Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”
In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.
At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.
A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.
The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).
When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).
“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”
For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.
According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.
Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”
Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.
Dr. Elman reported having no financial disclosures.
FROM AAD 20
ACIP approves flu vaccine recommendations for 2020-2021
– Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.
The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.
The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.
Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.
Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.
Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.
Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.
New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.
ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”
The ACIP members had no financial conflicts to disclose.
– Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.
The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.
The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.
Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.
Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.
Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.
Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.
New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.
ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”
The ACIP members had no financial conflicts to disclose.
– Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.
The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.
The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.
Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.
Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.
Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.
Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.
New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.
ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”
The ACIP members had no financial conflicts to disclose.
In scleroderma, GERD questionnaires are essential tools
Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.
“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”
Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.
The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.
The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.
The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.
When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.
Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.
“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”
Dr. Frech reported having no financial conflicts regarding her presentation.
Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.
“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”
Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.
The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.
The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.
The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.
When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.
Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.
“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”
Dr. Frech reported having no financial conflicts regarding her presentation.
Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.
“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”
Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.
The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.
The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.
The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.
When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.
Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.
“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”
Dr. Frech reported having no financial conflicts regarding her presentation.
FROM SOTA 2020
Belimumab safely improved renal function in lupus nephritis patients
compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.
“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m2 and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.
Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m2 and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.
“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.
Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.
compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.
“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m2 and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.
Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m2 and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.
“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.
Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.
compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.
“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m2 and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.
Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m2 and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.
“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.
Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.
FROM THE EULAR 2020 E-CONGRESS
Antinuclear antibody test interpretation guidance gets updated
New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.
ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.
“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.
There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.
In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.
The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.
Which test methodology to use?
There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?
The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”
Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.
“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”
The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.
“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.
In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”
Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.
New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.
ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.
“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.
There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.
In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.
The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.
Which test methodology to use?
There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?
The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”
Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.
“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”
The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.
“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.
In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”
Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.
New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.
ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.
“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.
There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.
In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.
The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.
Which test methodology to use?
There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?
The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”
Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.
“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”
The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.
“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.
In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”
Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.
FROM THE EULAR 2020 E-CONGRESS
Be vigilant for scleroderma renal crisis
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
FROM SOTA 2020
EULAR’s COVID-19 recommendations offer no surprises
As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.
Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.
“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”
The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”
The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”
From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.
The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.
There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.
Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.
The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.
If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.
On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.
“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.
“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”
Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”
One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.
Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.
“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”
SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.
As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.
Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.
“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”
The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”
The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”
From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.
The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.
There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.
Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.
The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.
If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.
On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.
“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.
“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”
Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”
One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.
Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.
“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”
SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.
As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.
Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.
“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”
The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”
The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”
From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.
The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.
There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.
Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.
The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.
If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.
On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.
“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.
“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”
Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”
One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.
Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.
“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”
SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.
FROM THE EULAR 2020 E-CONGRESS
Age leads COVID-19 hospitalization risk factors in RMDs
Being aged older than 65 years was associated with the highest risk of people with rheumatic and musculoskeletal diseases (RMDs) needing hospital treatment for COVID-19, according to the first results to be reported from ReCoVery, the German national COVID-19 registry.
Older patients with RMDs were five times more likely than younger patients to be hospitalized if they tested positive for SARS‑CoV‑2 and developed COVID-19 (odds ratio, 5.1; 95% confidence interval, 2.3-11.4).
The likelihood of hospitalization was also significantly increased by the current or prior use of glucocorticoids (OR, 2.59; 95% CI, 1.2-5.4) and by the presence of cardiovascular disease (OR, 2.27; 95% CI, 1.2-5.4).
“The register is a joint initiative of the German Society for Rheumatology and the Justus Liebig University in Giessen,” explained Anne Regierer, MD, during a live session of the annual European Congress of Rheumatology, held online this year due to COVID-19.
“The current pandemic has changed all of our lives. For patients it brought a lot of uncertainty and fears,” said Dr. Regierer, of the German Rheumatism Research Center Berlin.
“The risk of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases [IRD] is still largely unknown. We still don’t know whether they have a high risk of getting the infection or whether they have a higher risk of a severer case ... therefore there’s an urgent need to have data to generate evidence for the management of our patients.”
Launched at the end of March 2020, the German registry now includes data on 251 patients – 194 of whom have recovered – provided by more than 200 registered rheumatologists. The registry data have now been integrated into the EULAR COVID-19 Database, which is itself part of a global effort to better understand and optimally manage RMD patients during the pandemic.
“The data presented by Dr. Regierer looked at similar outcomes and found quite similar results, which is reassuring,” Kimme Hyrich, MD, PhD, professor of epidemiology at the University of Manchester (England) and a consultant rheumatologist in the Kellgren Centre for Rheumatology at Manchester University Hospitals NHS Foundation Trust, said in an interview.
“We are very grateful for this collaboration [with the German society and others]. Our first publication has looked at hospitalization, but with more data we may have the opportunity to look at less-common outcomes [e.g. death, other COVID complications] or within individual diseases or treatments. So far I don’t think we will come to a different conclusion,” observed Dr. Hyrich, who is on the steering committee for the EULAR COVID-19 Database.
“These initial data are reassuring in that the majority of cases of COVID reported to our database have recovered, including those who were hospitalized,” she said.
Current EULAR advice is to continue treatment with glucocorticoids in patients who are being chronically treated, but to use them at the lowest possible dose.
The objectives of this first analysis of the German registry was to provide a description of the patients who did and did not require hospitalization and those who needed ventilation, as well as look at possible risk factors for hospitalization.
Dr. Regierer reported that, of 192 patients they included – all with a positive lab test for SARS-CoV-2 – 128 (67%) did not require hospital admission. Of those that did (n = 64), 43 (22%) did not need ventilation and 21 (11%) did. Fifteen patients died, all of whom had been hospitalized, and all but one of them had needed ventilation.
Concerning the characteristics of the patients, those who needed hospital treatment with and without ventilation were older than those who were not admitted (70 vs. 65 vs. 54 years, respectively).
“Looking at the sexes, the gender distribution is also interesting. We see 69% females in the nonhospitalized patients, 65% of the inpatients without ventilation, but only 43% females in the ventilated patients. So in this group, the male patients are the majority,” Dr. Regierer observed.
Just over half of all patients in the nonhospitalized and the hospitalized without ventilation groups had IRD in remission, but those in the hospitalized with ventilation group less than one-fifth had their IRD under control.
“Of course we have to keep in mind the small sample sizes,” Dr. Regierer said, but the distribution of patients by disease type was “what you’d expect in clinical care.” The majority of patients in each of the three groups had RA (47%, 56%, and 57%), followed by psoriatic arthritis (19%, 7%, and 14%), axial spondyloarthritis (11%, 5%, and 0%), systemic lupus erythematosus (6%, 2%, and 0%), and vasculitis (1%, 5%, and 5%).
Patients who were hospitalized with and without ventilation were more likely to have more than one comorbidity than those who were not hospitalized with COVID-19.
“The most frequent comorbidity was cardiovascular disease with 58% and 76% in the inpatient groups,” Dr. Regierer reported. One-third of the nonhospitalized patients had a cardiovascular comorbidity.
“If we look at pulmonary disease, we see that 38% of the ventilator patients had an underlying pulmonary disease,” she added. This was in comparison with 19% of the hospitalized without ventilation and 13% of the nonhospitalized patients. Diabetes was another common comorbidity in hospitalized patients with (16%) and without (19%) ventilation versus just 2% of nonhospitalized patients. While these and other comorbidities such as chronic renal insufficiency were associated with higher odds ratios in the multivariate risk factor analysis, they did not reach statistical significance.
With regard to RMD treatments, more than 60% of patients in the hospitalized group had received treatment with glucocorticoids versus 37% of those who did not get admitted. No differences were seen for the other treatments.
Interestingly, “female sex, remission, and use of NSAIDs have an odds ratio smaller than 1. So there might be a lower risk of hospitalization associated with these factors,” Dr. Regierer said.
Dr. Regierer has received grant support and is part of speaker’s bureaus for a variety of pharmaceutical companies. Dr. Hyrich disclosed grant income from Bristol-Myers Squibb, UCB, and Pfizer, and receiving speaker fees from AbbVie.
Being aged older than 65 years was associated with the highest risk of people with rheumatic and musculoskeletal diseases (RMDs) needing hospital treatment for COVID-19, according to the first results to be reported from ReCoVery, the German national COVID-19 registry.
Older patients with RMDs were five times more likely than younger patients to be hospitalized if they tested positive for SARS‑CoV‑2 and developed COVID-19 (odds ratio, 5.1; 95% confidence interval, 2.3-11.4).
The likelihood of hospitalization was also significantly increased by the current or prior use of glucocorticoids (OR, 2.59; 95% CI, 1.2-5.4) and by the presence of cardiovascular disease (OR, 2.27; 95% CI, 1.2-5.4).
“The register is a joint initiative of the German Society for Rheumatology and the Justus Liebig University in Giessen,” explained Anne Regierer, MD, during a live session of the annual European Congress of Rheumatology, held online this year due to COVID-19.
“The current pandemic has changed all of our lives. For patients it brought a lot of uncertainty and fears,” said Dr. Regierer, of the German Rheumatism Research Center Berlin.
“The risk of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases [IRD] is still largely unknown. We still don’t know whether they have a high risk of getting the infection or whether they have a higher risk of a severer case ... therefore there’s an urgent need to have data to generate evidence for the management of our patients.”
Launched at the end of March 2020, the German registry now includes data on 251 patients – 194 of whom have recovered – provided by more than 200 registered rheumatologists. The registry data have now been integrated into the EULAR COVID-19 Database, which is itself part of a global effort to better understand and optimally manage RMD patients during the pandemic.
“The data presented by Dr. Regierer looked at similar outcomes and found quite similar results, which is reassuring,” Kimme Hyrich, MD, PhD, professor of epidemiology at the University of Manchester (England) and a consultant rheumatologist in the Kellgren Centre for Rheumatology at Manchester University Hospitals NHS Foundation Trust, said in an interview.
“We are very grateful for this collaboration [with the German society and others]. Our first publication has looked at hospitalization, but with more data we may have the opportunity to look at less-common outcomes [e.g. death, other COVID complications] or within individual diseases or treatments. So far I don’t think we will come to a different conclusion,” observed Dr. Hyrich, who is on the steering committee for the EULAR COVID-19 Database.
“These initial data are reassuring in that the majority of cases of COVID reported to our database have recovered, including those who were hospitalized,” she said.
Current EULAR advice is to continue treatment with glucocorticoids in patients who are being chronically treated, but to use them at the lowest possible dose.
The objectives of this first analysis of the German registry was to provide a description of the patients who did and did not require hospitalization and those who needed ventilation, as well as look at possible risk factors for hospitalization.
Dr. Regierer reported that, of 192 patients they included – all with a positive lab test for SARS-CoV-2 – 128 (67%) did not require hospital admission. Of those that did (n = 64), 43 (22%) did not need ventilation and 21 (11%) did. Fifteen patients died, all of whom had been hospitalized, and all but one of them had needed ventilation.
Concerning the characteristics of the patients, those who needed hospital treatment with and without ventilation were older than those who were not admitted (70 vs. 65 vs. 54 years, respectively).
“Looking at the sexes, the gender distribution is also interesting. We see 69% females in the nonhospitalized patients, 65% of the inpatients without ventilation, but only 43% females in the ventilated patients. So in this group, the male patients are the majority,” Dr. Regierer observed.
Just over half of all patients in the nonhospitalized and the hospitalized without ventilation groups had IRD in remission, but those in the hospitalized with ventilation group less than one-fifth had their IRD under control.
“Of course we have to keep in mind the small sample sizes,” Dr. Regierer said, but the distribution of patients by disease type was “what you’d expect in clinical care.” The majority of patients in each of the three groups had RA (47%, 56%, and 57%), followed by psoriatic arthritis (19%, 7%, and 14%), axial spondyloarthritis (11%, 5%, and 0%), systemic lupus erythematosus (6%, 2%, and 0%), and vasculitis (1%, 5%, and 5%).
Patients who were hospitalized with and without ventilation were more likely to have more than one comorbidity than those who were not hospitalized with COVID-19.
“The most frequent comorbidity was cardiovascular disease with 58% and 76% in the inpatient groups,” Dr. Regierer reported. One-third of the nonhospitalized patients had a cardiovascular comorbidity.
“If we look at pulmonary disease, we see that 38% of the ventilator patients had an underlying pulmonary disease,” she added. This was in comparison with 19% of the hospitalized without ventilation and 13% of the nonhospitalized patients. Diabetes was another common comorbidity in hospitalized patients with (16%) and without (19%) ventilation versus just 2% of nonhospitalized patients. While these and other comorbidities such as chronic renal insufficiency were associated with higher odds ratios in the multivariate risk factor analysis, they did not reach statistical significance.
With regard to RMD treatments, more than 60% of patients in the hospitalized group had received treatment with glucocorticoids versus 37% of those who did not get admitted. No differences were seen for the other treatments.
Interestingly, “female sex, remission, and use of NSAIDs have an odds ratio smaller than 1. So there might be a lower risk of hospitalization associated with these factors,” Dr. Regierer said.
Dr. Regierer has received grant support and is part of speaker’s bureaus for a variety of pharmaceutical companies. Dr. Hyrich disclosed grant income from Bristol-Myers Squibb, UCB, and Pfizer, and receiving speaker fees from AbbVie.
Being aged older than 65 years was associated with the highest risk of people with rheumatic and musculoskeletal diseases (RMDs) needing hospital treatment for COVID-19, according to the first results to be reported from ReCoVery, the German national COVID-19 registry.
Older patients with RMDs were five times more likely than younger patients to be hospitalized if they tested positive for SARS‑CoV‑2 and developed COVID-19 (odds ratio, 5.1; 95% confidence interval, 2.3-11.4).
The likelihood of hospitalization was also significantly increased by the current or prior use of glucocorticoids (OR, 2.59; 95% CI, 1.2-5.4) and by the presence of cardiovascular disease (OR, 2.27; 95% CI, 1.2-5.4).
“The register is a joint initiative of the German Society for Rheumatology and the Justus Liebig University in Giessen,” explained Anne Regierer, MD, during a live session of the annual European Congress of Rheumatology, held online this year due to COVID-19.
“The current pandemic has changed all of our lives. For patients it brought a lot of uncertainty and fears,” said Dr. Regierer, of the German Rheumatism Research Center Berlin.
“The risk of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases [IRD] is still largely unknown. We still don’t know whether they have a high risk of getting the infection or whether they have a higher risk of a severer case ... therefore there’s an urgent need to have data to generate evidence for the management of our patients.”
Launched at the end of March 2020, the German registry now includes data on 251 patients – 194 of whom have recovered – provided by more than 200 registered rheumatologists. The registry data have now been integrated into the EULAR COVID-19 Database, which is itself part of a global effort to better understand and optimally manage RMD patients during the pandemic.
“The data presented by Dr. Regierer looked at similar outcomes and found quite similar results, which is reassuring,” Kimme Hyrich, MD, PhD, professor of epidemiology at the University of Manchester (England) and a consultant rheumatologist in the Kellgren Centre for Rheumatology at Manchester University Hospitals NHS Foundation Trust, said in an interview.
“We are very grateful for this collaboration [with the German society and others]. Our first publication has looked at hospitalization, but with more data we may have the opportunity to look at less-common outcomes [e.g. death, other COVID complications] or within individual diseases or treatments. So far I don’t think we will come to a different conclusion,” observed Dr. Hyrich, who is on the steering committee for the EULAR COVID-19 Database.
“These initial data are reassuring in that the majority of cases of COVID reported to our database have recovered, including those who were hospitalized,” she said.
Current EULAR advice is to continue treatment with glucocorticoids in patients who are being chronically treated, but to use them at the lowest possible dose.
The objectives of this first analysis of the German registry was to provide a description of the patients who did and did not require hospitalization and those who needed ventilation, as well as look at possible risk factors for hospitalization.
Dr. Regierer reported that, of 192 patients they included – all with a positive lab test for SARS-CoV-2 – 128 (67%) did not require hospital admission. Of those that did (n = 64), 43 (22%) did not need ventilation and 21 (11%) did. Fifteen patients died, all of whom had been hospitalized, and all but one of them had needed ventilation.
Concerning the characteristics of the patients, those who needed hospital treatment with and without ventilation were older than those who were not admitted (70 vs. 65 vs. 54 years, respectively).
“Looking at the sexes, the gender distribution is also interesting. We see 69% females in the nonhospitalized patients, 65% of the inpatients without ventilation, but only 43% females in the ventilated patients. So in this group, the male patients are the majority,” Dr. Regierer observed.
Just over half of all patients in the nonhospitalized and the hospitalized without ventilation groups had IRD in remission, but those in the hospitalized with ventilation group less than one-fifth had their IRD under control.
“Of course we have to keep in mind the small sample sizes,” Dr. Regierer said, but the distribution of patients by disease type was “what you’d expect in clinical care.” The majority of patients in each of the three groups had RA (47%, 56%, and 57%), followed by psoriatic arthritis (19%, 7%, and 14%), axial spondyloarthritis (11%, 5%, and 0%), systemic lupus erythematosus (6%, 2%, and 0%), and vasculitis (1%, 5%, and 5%).
Patients who were hospitalized with and without ventilation were more likely to have more than one comorbidity than those who were not hospitalized with COVID-19.
“The most frequent comorbidity was cardiovascular disease with 58% and 76% in the inpatient groups,” Dr. Regierer reported. One-third of the nonhospitalized patients had a cardiovascular comorbidity.
“If we look at pulmonary disease, we see that 38% of the ventilator patients had an underlying pulmonary disease,” she added. This was in comparison with 19% of the hospitalized without ventilation and 13% of the nonhospitalized patients. Diabetes was another common comorbidity in hospitalized patients with (16%) and without (19%) ventilation versus just 2% of nonhospitalized patients. While these and other comorbidities such as chronic renal insufficiency were associated with higher odds ratios in the multivariate risk factor analysis, they did not reach statistical significance.
With regard to RMD treatments, more than 60% of patients in the hospitalized group had received treatment with glucocorticoids versus 37% of those who did not get admitted. No differences were seen for the other treatments.
Interestingly, “female sex, remission, and use of NSAIDs have an odds ratio smaller than 1. So there might be a lower risk of hospitalization associated with these factors,” Dr. Regierer said.
Dr. Regierer has received grant support and is part of speaker’s bureaus for a variety of pharmaceutical companies. Dr. Hyrich disclosed grant income from Bristol-Myers Squibb, UCB, and Pfizer, and receiving speaker fees from AbbVie.
FROM THE EULAR 2020 E-CONGRESS
Most rheumatology drugs don’t increase COVID-19 hospitalization risk
The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.
“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”
Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.
In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.
The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.
“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.
As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.
Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.
Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.
“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”
“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”
It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.
“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.
The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.
Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.
Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.
“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”
This article first appeared on Medscape.com.
The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.
“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”
Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.
In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.
The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.
“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.
As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.
Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.
Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.
“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”
“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”
It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.
“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.
The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.
Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.
Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.
“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”
This article first appeared on Medscape.com.
The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.
“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”
Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.
In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.
The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.
“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.
As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.
Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.
Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.
“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”
“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”
It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.
“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.
The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.
Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.
Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.
“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”
This article first appeared on Medscape.com.
Avacopan notches a win in ANCA-associated vasculitis
Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.
The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.
“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.
The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.
They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.
Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.
The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.
“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
Making sense of the results
The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”
Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”
“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”
The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.
“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
Study details
ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).
However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).
At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).
Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m2; P = .029).
“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.
Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.
The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).
The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.
SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.
Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.
The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.
“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.
The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.
They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.
Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.
The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.
“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
Making sense of the results
The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”
Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”
“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”
The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.
“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
Study details
ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).
However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).
At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).
Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m2; P = .029).
“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.
Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.
The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).
The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.
SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.
Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.
The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.
“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.
The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.
They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.
Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.
The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.
“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
Making sense of the results
The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”
Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”
“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”
The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.
“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
Study details
ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).
However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).
At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).
Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m2; P = .029).
“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.
Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.
The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).
The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.
SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.
FROM EULAR 2020 E-CONGRESS