Ann Rheum Dis Research Articles

Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis

BackgroundThe increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468.). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice.MethodsA monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out.ResultsIn the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed.ConclusionsIn our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

The History of Macrophage Activation Syndrome in Autoimmune Diseases.

In 1979, it became recognized in the literature that what we call hemophagocytic lymphohistiocytosis (HLH) was a nonmalignant disease of histiocytes. Subsequently a familial form and a secondary form of HLH were differentiated. When HLH is secondary to an autoimmune disease, rheumatologists refer to this entity as macrophage activation syndrome (MAS) to differentiate it from HLH itself. Although the first cases of MAS likely appeared in the literature in the 1970s, it was not until 1985 that the term activated macrophages was used to describe patients with systemic juvenile idiopathic arthritis (sJIA) complicated by MAS and the term macrophage activation syndrome first appeared in the title of a paper in 1993.MAS is one of the many types of secondary HLH and should not be confused with primary HLH. Experience has taught that MAS secondary to different autoimmune diseases is not equal. In the 30years since initial description in patients with sJIA, the clinical spectrum, diseases associated with MAS, therapy, and understanding the pathogenesis have all made significant gains. The diagnostic/classification criteria for MAS secondary to sJIA, SLE, RA, and KD differ based on the different laboratory abnormalities associated with each (Ahn et al., J Rheumatol 44:996-1003, 2017; Han et al., Ann Rheum Dis 75:e44, 2016; Ravelli et al., Ann Rheum Dis 75:481-489, 2016; Borgia et al., Arthritis Rheumatol 70:616-624, 2018). These examples include the thrombocytosis associated with sJIA, a chronic generalized activation of the immune system, leading to elevations of fibrinogen and sIL-2R, low platelet count associated with SLE, and more acute inflammation associated with KD. Therefore, individual diagnostic criteria are required, and they all differ from the diagnostic criteria for HLH, which are based on a previously non-activated immune system (Ahn et al., J Rheumatol 44:996-1003, 2017; Han et al., Ann Rheum Dis 75:e44, 2016; Ravelli et al., Ann Rheum Dis 75:481-489, 2016; Borgia et al., Arthritis Rheumatol 70:616-624, 2018; Henter et al., Pediatr Blood Cancer 48:124-131, 2007). This helps to explain why the HLH diagnostic criteria do not perform well in MAS.The initial treatment remains high-dose steroids and IVIG followed by the use of a calcineurin inhibitor for resistant cases. IVIG can be used if there is a concern about malignancy to wait for appropriate investigations or with steroids. Interluekin-1 inhibition is now the next therapy if there is a failure to respond to steroids and calcineurin inhibitors. Advances in understanding the mechanisms leading to MAS, which has been greatly aided by the use of mouse models of MAS and advances in genome sequencing, offer a bright future for more specific therapies. More recent therapies are directed to specific cytokines involved in the pathogenesis of MAS and can lead to decreases in the morbidity and mortality associated with MAS. These include therapies directed to inhibiting the JAK/STAT pathway and/or specific cytokines, interleukin-18 and gamma interferon, which are currently being studied in MAS. These more specific therapies may obviate the need for nonspecific immunosuppressive therapies including high-dose prolonged steroids, calcineurin inhibitors, and etoposide.

Some Patients with Suspected Thrombocytopathy Actually Have Ehlers-Danlos Syndrome; Clinical and Prognostic Implications

Thrombocytopathy is the most likely diagnosis for patients with easy bruising and/or mucous bleeding and normal platelet counts. However, in a small proportion of these patients, all hemostatic tests are normal and the right diagnosis is actually Ehlers-Danlos syndrome (EDS). EDS is a heterogeneous group of genetic connective tissue disorders, characterized by joint hypermobility, skin and vascular fragility, and tissue friability; the most recent classification describes 13 clinical subtypes of EDS with mutations in 19 different genes (Malfait et al. Am J Med Genet C Semin Med Genet. 2017;175:8). Besides joint hypermobility, cutaneous-mucosal bleeding of variable intensity is observed in the majority of patients. In the vascular subtype of EDS, arterial aneurysms, dissections and ruptures of arteries and arteriovenous fistulas are detected as manifestations of vascular fragility; less frequently, such vascular pathologies can also appear in other types of EDS (Malfait. Matrix Biol 2018;71-72:380). Based on our experience on patients with suspected thrombocytopathy but finally diagnosed of EDS, our objective is to attract the attention of hematologists to the possible diagnosis of EDS for patients with cutaneous-mucosal bleeding without any platelet or coagulation abnormality. This will lead to the adoption of the necessary measures to confirm diagnosis and to prevent complications, sometimes serious, of EDS. We studied 8 patients, all women, with cutaneous-mucosal bleeding referred to our consultation as suspected thrombocytopathies. The main characteristics of the patients are shown in Table 1. Platelet counts, platelet function, and coagulation tests were normal in all cases. However, the evaluation of their articular mobility showed generalized hypermobility with the Beighton score (Beighton. Ann Rheum Dis 1973;32:413). Two of the patients (cases 3 and 4) presented carotid-cavernous fistulas that led to loss of vision on the corresponding side. Case 3 was a 6-year-old girl with mild cutaneous bleeding and no other clinical manifestations. His mother, with a mild hemorrhagic tendency and no other symptoms, had died at the age of 35 from a massive peritoneal hemorrhage secondary to spontaneous rupture of the spleen; the observation of marked tissue fragility, at surgery and at necropsy, established the diagnosis of EDS. The girl's clinical bleeding, together with normal hemostatic tests and family history, suggested the diagnosis of EDS. This patient developed well, but, at the age of 18, a right carotid-cavernous fistula was diagnosed. Case 4 was a 51-year-old woman with a history of bronchial asthma, duodenal ulcer, gallstones, shoulder dislocations and bleeding tendency. At the age of 45, she had suffered a left carotid-cavernous fistula. Because the results of all hemostasis tests were normal, an exploration of her joint mobility was performed resulting in a positive Beighton score. This suggested the diagnosis of EDS. At the age of 55, we were informed that the patient had died, in another center, from massive bleeding in a surgical intervention for colon diverticula. Although it is not frequent, there is the possibility that a patient with bleeding and without hemostatic abnormalities suffers from EDS which, in our experience, can lead to serious vascular complications, even in patients with mild symptomatology. We recommend in these patients to perform a test as simple as the Beighton score. If the result indicates a possible EDS, we suggest referring the patient to all the necessary specialists to confirm the diagnosis and carry out proper patient care and prevention of complications. Moreover, bearing in mind the frequency of carotid-cavernous fistulas with orbital involvement in our case series, we suggest the patient should be informed about the ophthalmologic symptoms of this vascular complication (Fay et al. Clin Neuroradiol 2021;31:165). The most characteristic symptom is the anteroposterior displacement of the eyeball with each heartbeat. Other findings are proptosis, difficulty in making eye movements, chemosis, and conjunctival-scleral hyperemia with vascular tortuosity (Fig. 1). The ophthalmologist may also find venous tortuosity in the fundus, intraocular hypertension, with or without associated glaucoma, and enlargement of the superior ophthalmic vein on imaging tests. The recommended treatment is embolization of the fistula.

Industry Payments to United States Rheumatologist-Authors of Publications in High-Impact Rheumatology Journals.

A skewed percentage of industry payments goes to "key opinion leaders" (KOLs) whose prominence and influence has increased with time. Given that KOL is neither precisely defined nor quantifiable, we turned to the level of industry payments as a surrogate quantifiable metric and assessed the associations between industry payments to US rheumatologists and their authorships of publications in high-impact rheumatology journals. Payments to US rheumatologists during the 2015-2020 interval were obtained from the Centers for Medicare and Medicaid Services Open Payments database, and authorships were tallied for calendar year 2021 publications in the four rheumatology journals (Lancet Rheumatol, Nat Rev Rheumatol, Ann Rheum Dis, Arthritis Rheumatol) with the highest 2021 journal impact factors and journal citation indicators. Differences between groups were determined by chi-squared test, unpaired Student's t-test, one-way analysis of variance (ANOVA), Mann-Whitney rank sum test, and Kruskal-Wallis one-way ANOVA on ranks. Correlations were calculated using Spearman rank order. A P value ≤0.05 was considered significant. There were 278 individual US rheumatologists who received industry payments and served as authors of publications in the four high-impact rheumatology journals. Non-research-associated payments to these individuals strongly correlated with research-associated payments. Payments to male US rheumatologists were greater than those to their female counterparts, and payments strongly correlated with the number of publications among male authors but only weakly, and often not significantly, among female authors. A substantial fraction of the authorships in calendar year 2021 publications in four high-impact rheumatology journals arose from a very small percentage of all US rheumatologists who had received industry payments during the 2015-2020 interval. Payments to male US rheumatologist-authors were strikingly different from those to female US rheumatologist-authors, and further investigation is needed to explain the glaring difference in payments.

In relapsing AAV with rituximab-induced remission, maintenance rituximab vs. azathioprine reduced relapse at ≥32 mo.

Smith RM, Jones RB, Specks U, et al; RITAZAREM co-investigators. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial. Ann Rheum Dis. 2023;82:937-944. 36958796.

#6843 CITATION CLASSICS IN LUPUS NEPHRITIS: A BIBLIOMETRIC ANALYSIS

Abstract Background and Aims Lupus nephritis is an important risk factor for morbidity and mortality in systemic lupus erythematosus. During the past three decades, extensive research has been done to address this important complication and devise better management strategies. In this article we aimed to perform a thorough assessment of the research productivity in lupus nephritis by identifying the 100 most-cited articles in lupus nephritis. Methods The top 100 most-cited English language articles on lupus nephritis from 1990 were examined by bibliometric analysis from the Google Scholar database of ‘Harzing's Publish or Perish’ software. These articles were subsequently analysed in detail and the chief characteristics are presented here. Results From 1990-2022, there were 111358 citations with 3480 cites/year and an average of 111 cites/paper. Thirty articles had greater than 400 citations, with 9 having more than1000 citations. Majority of the publications were from the United States of America (46%) with maximum publications from the National Institute of Health (NIH), Bethesda. Among these 100 most-cited articles, there were a median of 7 (5-12) authors per article with a mean of 9.6 authors. Twenty-six percent of the top-100 most-cited articles were randomized controlled trials while cohort and in-vivo studies addressing pathophysiology and biopsy related data accounted for one-fourth each. Among rheumatology journals, ‘Arthritis Rheum’, ‘Ann Rheum Dis’ and ‘Lupus’ were the most preferred journals for researchers working on lupus nephritis. Conclusion This article gives an overview of the research productivity, landmark publications and emerging trends in lupus nephritis. Increased emphasis on high-quality data from randomized controlled trials is revolutionising the management of lupus nephritis.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Aortic dissection secondary to giant cell arteritis.

British Journal of Hospital MedicineEarly view Case ReportAortic dissection secondary to giant cell arteritisConnor Cotton, Sarah Chatharoo, Pankaj ChaturvediConnor CottonCorrespondence to: Connor Cotton; E-mail Address: [email protected]Department of Diabetes and Endocrinology, Doncaster and Bassetlaw Teaching Hospitals NHS Trust, Worksop, UKSearch for more papers by this author, Sarah ChatharooDepartment of Diabetes and Endocrinology, Doncaster and Bassetlaw Teaching Hospitals NHS Trust, Worksop, UKSearch for more papers by this author, Pankaj ChaturvediDepartment of Diabetes and Endocrinology, Doncaster and Bassetlaw Teaching Hospitals NHS Trust, Worksop, UKSearch for more papers by this authorConnor Cotton; Sarah Chatharoo; Pankaj ChaturvediPublished Online:17 Apr 2023https://doi.org/10.12968/hmed.2022.0529AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View article References Agard C, Ponge T, Fradet G et al.. Giant cell arteritis presenting with aortic dissection: two cases and review of the literature. Scand J Rheumatol. 2006;35(3):233–236. https://doi.org/10.1080/03009740500395252 Crossref, Medline, Google Scholarde Boysson H, Espitia O, Samson M et al.. Giant cell arteritis-related aortic dissection: a multicenter retrospective study. Semin Arthritis Rheum. 2021;51(2):430–435. https://doi.org/10.1016/j.semarthrit.2021.03.001 Crossref, Medline, Google ScholarEvans JM, O'Fallon WM, Hunder GG. Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis: a population-based study. Ann Intern Med. 1995;122(7):502. https://doi.org/10.7326/0003-4819-122-7-199504010-00004 Crossref, Medline, Google ScholarHiratzka LF, Bakris GL, Beckman JA et al.. Faculty opinions recommendation of 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/sir/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010;121(13): e266–369. https://doi.org/10.1161/CIR.0b013e3181d4739e Medline, Google ScholarKermani TA, Warrington KJ, Crowson CS et al.. Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis. Ann Rheum Dis. 2013;72(12):1989–1994. https://doi.org/10.1136/annrheumdis-2012-202408 Crossref, Medline, Google ScholarMackie SL, Dejaco C, Appenzeller C et al.. British society for rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology. 2020;59(3):e01–e23. https://doi.org/10.1093/rheumatology/kez672 Crossref, Medline, Google ScholarNayar AK, Casciello M, Slim JN, Slim AM. Fatal aortic dissection in a patient with giant cell arteritis: a case report and review of the literature. Case Rep Vasc Med. 2013;2013:1–4. https://doi.org/10.1155/2013/590721 Google Scholar FiguresReferencesRelatedDetails Ahead of PrintISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 17 April 2023 Information© MA Healthcare LimitedAcknowledgementsThe authors would like to thank Sarah Gardner, Library and Information Service, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust Knowledge, Doncaster, for her help with the literature search.PDF download

Preclinical or subclinical rheumatoid arthritis-associated interstitial lung disease: misleading terms with potentially deleterious consequences

Interstitial lung disease (ILD) is a leading cause of mortality in patients with rheumatic diseases, including rheumatoid arthritis. 1 Olson AL Swigris JJ Sprunger DB et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011; 183: 372-378 Crossref PubMed Scopus (299) Google Scholar The 5-year mortality rate is twice as high in patients with rheumatoid arthritis-associated ILD than in patients with rheumatoid arthritis without ILD. 2 Hyldgaard C Hilberg O Pedersen AB et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017; 76: 1700-1706 Crossref PubMed Scopus (159) Google Scholar Moreover, a report showed that mortality rates in patients with disease codes for rheumatoid arthritis-associated ILD remained unchanged from 2005–18, even though the overall rheumatoid arthritis mortality rate declined during this time period. 3 Jeganathan N Nguyen E Sathananthan M Rheumatoid arthritis and associated interstitial lung disease: mortality rates and trends. Ann Am Thorac Soc. 2021; 18: 1970-1977 Crossref PubMed Scopus (6) Google Scholar Despite the evidence that ILD contributes to premature death in rheumatoid arthritis, screening for ILD in patients with rheumatoid arthritis is not routinely performed in clinical practice and numerous questions remain regarding the management of rheumatoid arthritis-associated ILD. 4 Kelly C Emery P Dieudé P Current issues in rheumatoid arthritis-associated interstitial lung disease. Lancet Rheumatol. 2021; 3: e798-e807 Summary Full Text Full Text PDF Scopus (6) Google Scholar

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

A Randomized, Placebo-Controlled, Phase 1 Study in Healthy Adult Volunteers of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALPN303, a Potent Dual BAFF/APRIL Antagonist for the Treatment of Autoimmune Cytopenias

Background B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are tumor necrosis factor superfamily (TNFSF) members that bind transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), B-cell maturation antigen, and/or BAFF receptor (BAFF-R) on B cells and together support B-cell development, survival, and differentiation into antibody-secreting cells (ASC). In preclinical studies, co-neutralization of BAFF and APRIL can directly suppress ASC and reduce circulating immunoglobulins. Autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) are diseases characterized by autoantibodies directed against red blood cells and platelets, respectively. Significantly higher levels of both BAFF and APRIL have been observed in the serum of patients with AIHA and ITP compared to healthy subjects, and polymorphisms in BAFF and TACI have been associated with ITP [Abdel-Hamid, et al., Am J Med, 2011; Emmerich, et al., Br J Haematol, 2007; Peng, et al., J Thromb Haemost, 2017; Yu, et al., Blood Adv, 2021]. Currently, there are no B cell targeting agents approved to treat AIHA or ITP. Rituximab, an anti-CD20 therapeutic which depletes CD20+ B cells, and thereby only indirectly reduces autoantibody production, has demonstrated some efficacy in both ITP [Neunert, et al., Blood, 2019] and AIHA [Jäger, et al., Blood Rev, 2019], though it is not approved for use in either indication. Belimumab, an anti-BAFF neutralizing antibody (Ab), has demonstrated encouraging efficacy in the treatment of ITP associated with systemic lupus erythematosus (SLE) [De Marchi, et al., Clin Exp Rheumatol, 2017] and also in combination with rituximab in patients with ITP [Mahévas, et al., Haematologica, 2021], but only had a modest impact on hematological manifestations in SLE patients [Manzi, et al., Ann Rheum Dis, 2012]. To address the shortcomings of existing B-cell-targeting agents, we have developed ALPN-303, an Fc fusion of an engineered TACI variant TNFRSF domain, which substantially improves upon the ligand affinity liabilities of wild type (WT) TACI, resulting in highly potent dual BAFF/APRIL inhibition superior to WT TACI-Fc, or to BAFF- or APRIL-specific monoclonal Abs. In preclinical studies, ALPN-303 demonstrates enhanced pharmacokinetic (PK) and immunomodulatory properties vs. WT TACI-Fc, which may translate to lower and/or less frequent doses in humans. ALPN-303 also suppresses autoantibodies and nephritis in mouse models of lupus. Taken together, these observations suggest that a potent dual BAFF/APRIL antagonist such as ALPN-303, by lowering pathogenic autoantibody levels, may be particularly beneficial in the treatment of antibody-related hematologic diseases, such as autoimmune cytopenias. Methods In this first-in-human study (NCT05034484), healthy adult volunteers have been enrolled in single ascending dose cohorts of intravenously (IV) or subcutaneously (SC) administered ALPN-303. For each IV cohort, the first 2 sentinel subjects are randomized 1:1 to receive ALPN-303 or placebo, followed by the remaining 4 subjects randomized 3:1 to receive ALPN-303 or placebo. SC cohorts are randomized 4:2 to receive a single SC dose of ALPN-303 or placebo. All subjects are followed to assess safety, PK, and pharmacodynamic (PD) effects including impacts on circulating immunoglobulins (Ig), and peripheral B-cell populations. Results ALPN-303 has been well tolerated in all cohorts evaluated to date and exhibits dose-dependent PK and expected PD effects, including dose-dependent reductions in circulating CD38+ (CD19+CD27+IgD-) ASC (Figure 1) and in serum Ig (Figure 2). To date, there have been no serious adverse events, and no events of cytokine release syndrome. Dose escalation will be complete by the time of the meeting; the presentation will include all available safety, PK, and PD data. Conclusions In this phase 1 study, ALPN-303 demonstrates acceptable preliminary safety and tolerability and exhibits dose-dependent PK and expected PD effects on circulating Ig and B-cell populations. These findings support future clinical development of ALPN-303 in patients with antibody-related diseases, including autoimmune cytopenias. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical and paraclinical features of small fiber neuropathy in Sjögren’s syndrome

Sjögren’s syndrome is a potentially treatable cause of Small Fiber Neuropathy (SFN)—a condition that severely affects patients’ quality of life. We therefore aimed to characterize patients with SFN and Sjögren’s syndrome to raise awareness of this disease and facilitate its early recognition as an essential step for appropriate treatment. In 97 SFN patients (median age 48 years, 77% female), we studied the clinical features associated with Sjögren’s syndrome compared to the idiopathic SFN subtype. According to the current ACR/EULAR classification criteria (Shiboski et al., Ann Rheum Dis 76:9–16, 2017), 24/97 individuals (25%, median age 48.5 years, 75% female) were diagnosed with Sjögren’s syndrome. We did not observe any differences in SFN-defining sensory plus symptoms. Furthermore, intraepidermal nerve fiber densities (IENFD) were significantly lower in patients with SFN and Sjögren’s syndrome (mean 2.6 ± 1.2/mm) compared to patients with idiopathic SFN (mean 3.2 ± 1.5/mm; p = 0.048). There were no significant group differences when analyzing cerebrospinal fluid (CSF) parameters. We conclude that Sjögren’s syndrome-associated SFN is difficult to distinguish from idiopathic forms based on initial clinical symptoms and CSF results. However, lower IENFD values in patients with Sjögren's syndrome-associated SFN might indicate a distinct different pathomechanism in this entity compared to idiopathic SFN.

DISSEMINATED HERPES ZOSTER VIRUS INFECTION FOLLOWING BARICITINIB IN COVID-19

DISSEMINATED HERPES ZOSTER VIRUS INFECTION FOLLOWING BARICITINIB IN COVID-19

A RARE CASE OF MASSIVE RENAL VEIN HEMORRHAGE IN TRANSPLANT FOR LUPUS NEPHRITIS END-STAGE RENAL DISEASE

A RARE CASE OF MASSIVE RENAL VEIN HEMORRHAGE IN TRANSPLANT FOR LUPUS NEPHRITIS END-STAGE RENAL DISEASE

Skin thickness affects the result of tuberculin skin test in systemic sclerosis

BackgroundSkin thickness is a prominent clinical feature of systemic sclerosis (SSc), but there is no consensus on the cut-off for a positive tuberculin skin test (TST) size and the limitation of the TST for a diagnosis of tuberculosis in SSc. We aimed to identify the cut-off size of an indurated TST and the sensitivity and specificity of the test for the diagnosis of tuberculosis in SSc patients.MethodsA cross-sectional study of 168 adult Thai SSc patients was conducted. The TST was done using 0.1 ml of purified protein derivatives via intradermal injection. The test was interpreted 72 h after testing.ResultsThe median age was 57.2 years. The majority (71.8%) had the diffuse cutaneous SSc subset. All the patients had a BCG vaccination at birth, and 17 (10.1%) had a tuberculosis infection. An indurated skin reaction size of 20 mm had the highest specificity for tuberculosis (99.3%: 95%CI 96.4–100) (ROC 0.53). The skin thickness—assessed using the modified Rodnan skin score (mRSS)—had a significant negative correlation with the reaction size (Rho -0.23; p = 0.003).ConclusionThe TST is not sufficiently sensitive for detecting TB infection in SSc patients, albeit a skin induration of ≥ 15 mm indicates a high specificity for tuberculosis infection. A high mRSS resulted in a smaller skin reaction size when using the TST, which has limited utility as a diagnostic for tuberculosis among SSc patients with severe skin thickness.The manuscript was presented as a poster presentation at the Annual European Congress of Rheumatology EULAR 2019 Madrid 12–15 June 2019. (Ann Rheum Dis. 2019;78(suppl 2): abstract FRI0347) http://dx.doi.org/10.1136/annrheumdis-2019-eular.1456

POS0934 EFFICACY OF UPADACITINIB ON PSORIATIC ARTHRITIS WITH AXIAL INVOLVEMENT DEFINED BY INVESTIGATOR ASSESSMENT AND PRO-BASED CRITERIA: RESULTS FROM TWO PHASE 3 STUDIES

BackgroundPatients with PsA and axial involvement have higher disease activity and greater reductions in quality of life;1 however, there are no accepted criteria for identifying axial involvement in PsA.ObjectivesThe objective of this post-hoc analysis is to assess the efficacy of upadacitinib (UPA), a Janus kinase inhibitor, on axial symptoms in patients with active PsA and axial involvement defined by investigator assessment and PRO-based criteria from two phase 3 SELECT trials.2,3MethodsPatients with active PsA (≥3 swollen joints and ≥3 tender joints) and prior inadequate response or intolerance to ≥1 non-biologic (SELECT-PsA 1) or ≥1 biologic (SELECT-PsA 2) DMARD were randomly assigned to once daily oral UPA 15 mg or 30 mg, placebo (PBO), or every other week subcutaneous adalimumab (ADA) 40 mg (SELECT-PsA 1 only).2,3 At baseline, axial involvement in PsA was determined by investigator assessment based on the totality of clinical information, such as duration and character of back pain, age of onset, and previous imaging. In addition to investigator assessment, PRO-based criteria for axial involvement (BASDAI ≥4 and BASDAI Question 2 ≥4 at baseline) were applied for this analysis to identify patients with active disease. Efficacy in the sub-group of patients defined using both investigator assessment and PRO-based criteria was evaluated at week 24 for UPA 15 mg vs PBO and ADA (SELECT-PsA 1 only). Data were analyzed using mixed-effect model repeated measures (MMRM) or non-responder imputation (NRI), with nominal P-values shown.ResultsBased on investigator assessment alone, 31.3% (n=534/1704) of patients in SELECT-PsA 1 and 34.2% (n=219/641) in SELECT-PsA 2 were defined as having axial involvement. When both investigator assessment and PRO-based criteria were applied, 23.1% (n=393/1704) of patients in SELECT-PsA 1, or 73.6% (n=393/534) of those defined using investigator assessment alone, and 27.5% (n=176/641) in SELECT-PsA 2, or 80.4% (n=176/219) using investigator assessment alone, met the combined criteria for axial involvement. In both studies, UPA 15 mg showed significantly greater clinical responses vs PBO at week 24 across all endpoints assessed (Figure 1). In SELECT-PsA 1, UPA showed numerically greater responses than ADA at week 24 across all BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints. The proportion of patients achieving ASDAS clinically important improvement (CII) at week 24 was significantly greater with UPA vs ADA based on nominal P-value.ConclusionPatients with active PsA and axial involvement defined by both investigator assessment and PRO-based criteria demonstrated statistically greater clinical responses related to their axial involvement with UPA 15 mg compared to PBO, and consistently numerically higher responses compared to ADA, at week 24 in the SELECT-PsA trials. Findings from this post-hoc analysis are consistent with previous data based on investigator assessment alone.4References[1]Mease PJ et al. J Rheumatol. 2018; 45(10):1389-96[2]McInnes IB et al. N Engl J Med. 2021; 384(13):1227-39[3]Mease PJ et al. Ann Rheum Dis. 2020; 80(3):312-20[4]Deodhar A et al. Arthritis Rheumatol. 2020; 72(Suppl 10)AcknowledgementsAbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, R Ranza Speakers bureau: AbbVie, Janssen, Novartis, and Pfizer, Consultant of: AbbVie, Janssen, Novartis, and Pfizer, Andrew Ostor Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche, francesco ciccia Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB, Grant/research support from: AbbVie, Celgene, Pfizer, Roche, and UCB, Laura Coates Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB, Grant/research support from: AbbVie, Celgene, Pfizer, Roche, and UCB, Simona Rednic Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, and Pfizer, Grant/research support from: AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Jessica A. Walsh Consultant of: AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Tianming Gao Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Apinya Lertratanakul Shareholder of: Formerly of AbbVie, Employee of: Former employee of AbbVie, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Fabiana Ganz Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kevin Douglas Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Boehringer Ingelheim, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, GSK, Lilly, Novartis, Pfizer and UCB

POS0805 GLUCOCORTICOID-RELATED ADVERSE EVENTS IN GIANT CELL ARTERITIS: APPLICATION OF THE GLUCOCORTICOID TOXICITY INDEX IN A MONOCENTRIC COHORT OF 140 PATIENTS

BackgroundOral glucocorticoids (GC) are the mainstay of treatment for giant cell arteritis (GCA) but chronic exposure to GC is associated with serious comorbidities.ObjectivesThe objective of this study was to determine the GC exposure and risk of GC-related adverse events (AEs) in GCA, validating the Glucocorticoid Toxicity Index (GTI) (1,2) in a cohort of real-world patients.Methods140 consecutive patients with GCA were enrolled in this retrospective monocentric study. All patients were older than 50 years of age, met the 1990 ACR criteria for GCA and/or had the evidence of a large vessel vasculitis at FDG-PET/CT scan. Patients’ clinical data were collected from clinical charts, calculating GC cumulative dose and GTI at baseline and in the following 5 years.Results140 patients were enrolled in the study: median (IQR) age at diagnosis 74 (67-79), Female: 97 (69%), Male: 43 (31%). According to vascular involvement patients were classified in cranial-GCA (C-GCA, n:91), large vessel-GCA (LV-GCA, n:21) and cranial and large vessel-GCA (LV-C-GCA, n:28). Furthermore, 50 (36%) patients were treated with only GC, 44 (31%) with GC+methotrexate (MTX), 46 (33%) with GC+tocilizumab (in 20 cases TCZ was started in the first 3 months after diagnosis: early-TCZ, in 26 cases after 3 months for relapses or AEs: late-TCZ).During the follow up, 57 (41%) patients presented at least one relapse. In the GC group 22 relapses in 18 patients were reported, in MTX group 33 relapses in 25 patients (with 15 relapses before and 18 after MTX start), in early-TCZ group no relapses were reported, in late-TCZ group 21 relapses in 14 patients (with 17 relapses before and 4 after TCZ start) were reported.Median cumulative GC doses after 1 and 5 years were respectively 7.9 (6.3-9.8) gr and 16.5 (13.8-18.9) gr in GC group, 8.7 (5.9-10.0) gr and 16.5 (13.2-20.7) gr in MTX group, 7.1 (5.5-8.0) gr and 13.3 (12.8-13.7) gr in early-TCZ and 7.7 (6.2-11.1) gr and 19.7 (12.2-23.8) gr in late-TCZ.Eighty-eight percent of patients developed at least one GC-AE, with infections and hypertension being the most common reported AEs (42% e 44%, respectively). Median GTI-CWS (Cumulative Worsening Score) after 1 year was 65 (20-137) in GC, 63 (10-95) in MTX, 51 (33-116) in TCZ-early, 44 (0-91) in TCZ-late. Median GTI-CWS after 5 years was 219 (118-240) in GC, 137 (65-206) in MTX, 147 (146-147) in TCZ-early, 200 (121-231) in TCZ-late. A correlation between GTI-CWS and the GC cumulative dose was found (after 5 years r: 0.295, p: 0.026).ConclusionChronic GC treatment is associated with a high risk of developing comorbidities. GTI score demonstrated to be an effective tool to assess GC-related AEs and proved to correlate with GC cumulative dose.TCZ confirmed its efficacy in reducing relapse rate, both in early and late-TCZ groups (3). TCZ showed for the first time in a real-life cohort a GC sparing effect, with a 19% reduction in GC cumulative dose and a 33% reduction in GTI-CWS in 5 years (comparing GC group vs early-TCZ group).

POS0939 BIMEKIZUMAB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 1, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO‑CONTROLLED STUDY

POS0939 BIMEKIZUMAB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 1, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO‑CONTROLLED STUDY

OP0148 THE ASAS CORE MEASUREMENT SET FOR AXIAL SPONDYLOARTHRITIS

BackgroundRecently, the core domains of the 20-years old core outcome set for ankylosing spondylitis were updated.1 The next step is to define the measurement core set, which includes at least one instrument for each domain.ObjectivesTo define the instruments for the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA).MethodsThe scientific committee invited an international working group representing all key stakeholders (patients, rheumatologists, health professionals and pharmaceutical industry). The instrument selection process is presented in Figure 1.Figure 1.Development process to determine the core measurement setResultsThe updated core measurement set for axSpA is shown in Table 1. This includes seven instruments for six domains that are mandatory for all trials: ASDAS and NRS patient global assessment for disease activity, NRS total back pain for pain, composite index for morning stiffness, NRS fatigue for fatigue, BASFI for physical function, and ASAS Health Index for overall functioning and health. There are 9 additional instruments for disease modifying drugs (DMARDs): two MRI activity scores (SPARCC SIJ and SPARCC spine) for disease activity, the three extra-musculoskeletal manifestations uveitis, IBD and psoriasis assessed as recommended by ASAS2, the three peripheral manifestations (44 swollen joint count, MASES and Dactylitis count2) and mSASSS for structural damage. The imaging outcomes are mandatory to be included at least in one trial for a drug that is considered to be a DMARD. The other instruments specific for DMARDs should be included in every trial. This core set is applicable to patients with radiographic and non-radiographic axSpA. Furthermore, 11 other instruments were also endorsed by ASAS and can additionally be used in axSpA trials: BASDAI, CRP, Berlin MRI-SIJ and MRI-spine activity scores for disease activity, NRS back pain at night for pain, severity (BASDAI Q5) and duration (BASDAI Q6) for morning stiffness, SF-36 for overall functioning and health, 66 swollen joint count and SPARCC enthesitis for peripheral manifestations and MRI-SIJ erosions scores (SPARCC SSS) for structural damage.Table 1.Updated core measurement set for axial spondyloarthritis.Instruments mandatory for all trialsDomainInstrument Disease activityASDASPatient global assessment of disease activity (NRS) PainNRS total back pain (BASDAI Q2) Morning stiffnessSeverity and duration (BASDAI (Q5+Q6)/2)) FatigueNRS fatigue (BASDAI Q1) Physical functionBASFI Overall functioning & healthASAS Health IndexAdditional instruments mandatory for disease modifying drugs trials Disease activitySPARCC MRI-SIJ*SPARCC MRI-spine* Extra-musculoskeletal manifestationsuveitis (ASAS CRF)2psoriasis (ASAS CRF)2inflammatory bowel disease (ASAS CRF)2 Peripheral manifestations44 Swollen joint countMASESDactylitis count (ASAS CRF)2 Structural damagemSASSS**Needs to be assessed at least once in a disease modifying drug programme; 2Dougados M, et al. Ann Rheum Dis 2012;71(6):1103-04. ASDAS: Ankylosing Spondylitis Disease Activity Score; NRS: Numerical Rate Scale; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; Q: question; BASFI: Bath Ankylosing Spondylitis Functional Index; SPARCC: SpondyloArthritis Research Consortium of Canada Scoring System; MRI: Magnetic Resonance Imaging; SIJ: Sacroiliac Joint; CRF: Case Report Form; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; mSASSS: modified Stoke Ankylosing Spondylitis Spinal Score.ConclusionThe previous core measurement set has been updated and endorsed by ASAS for the use in all axSpA trials.

OP0019 BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 2, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY

OP0019 BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 2, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY