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ObjectivesTo characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.MethodsWe performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.ResultsIn pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p

ObjectiveTo develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).MethodsThis international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.ResultsThe 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.ConclusionThese new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.

Objectives ANA-associated rheumatic and musculoskeletal (MSK) diseases (RMDs) [SLE, primary SS (pSS), scleroderma, inflammatory myositis, MCTD and UCTD] make up a disease spectrum with overlapping clinical and immunological features. MSK inflammation is common and impactful across ANA-associated RMDs. The objectives of this study were to evaluate MSK inflammation (ANA-associated arthritis) prevalence in a multidisease ANA-associated RMD study, assess its clinical impact across ANA-associated RMD diagnoses, propose new basket groupings of patients, and evaluate immunological profiles in legacy and new basket contexts. Methods An observational study enrolled patients with ANA-associated RMDs. Demographic variables, comorbidities, therapies, disease activity instruments [BILAG, SLEDAI, the EULAR SS disease activity index (ESSDAI), physician visual analogue scale (VAS)], patient-reported outcomes [SF36, FACIT-Fatigue, EQ5D, ICECAP-A, Work Productivity and Activity impairment (WPAI), patient VAS] and the biomarker profile (six-gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian mixture modelling (GMM). The clinical and immune features of new and legacy clusters were compared. Results Inflammatory MSK symptoms were prevalent across ANA-associated RMDs, in 213/294 patients. In ANA-associated arthritis patients, most variables did not differ between diagnoses, with the exception of the EQ5D-5L index and mobility domains (lower in MCTD/pSS, both P  < 0.05). FM and OA prevalence were similar across diagnoses. Therapy use differed significantly, the use of biologics being greatest in SLE (P  < 0.05). GMM yielded two multidisease clusters: High MSK disease activity (n  = 89) and low MSK disease activity (n  = 124). The high MSK disease activity cluster included all patients with active joint swelling, and they had significantly higher prednisolone usage, physician global assessment (PGA), Sm/RNP/SmRNP/chromatin positivity, Tetherin mean fluorescence intensity (MFI), and IFN Score-A activity, along with numerically lower FM and OA prevalence. Conclusion We defined ANA-associated arthritis, a more clinically and immunologically homogeneous population than existing RMD populations for trials, and a more prevalent population for therapies in the clinic. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) have revolutionized the management of SLE, providing patients with rapid symptomatic relief and preventing flares when maintained at low dosages. However, there are increasing concerns over GC-associated adverse effects and organ damage, which decrease patients' quality of life (QOL) and increase healthcare costs. This highlights the need to balance effective GC use and minimize toxicity in patients with SLE. Herein, we provide an overview of the theoretical considerations and clinical evidence, in addition to the variations and similarities across nine national and eight international recommendations regarding the use of GCs across SLE manifestations and how these compare with real-world usage. In line with this, we propose possible actions toward the goal of GC Stewardship to improve the QOL for patients with lupus while managing the disease burden. [ABSTRACT FROM AUTHOR]

Objectives To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. Methods The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. Results The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n  = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). Conclusions Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment. [ABSTRACT FROM AUTHOR]

Objectives Outcomes of therapy for LN are often suboptimal. Guidelines offer varied options for treatment of LN and treatment strategies may differ between clinicians and regions. We aimed to assess variations in the usual practice of UK physicians who treat LN. Methods We conducted an online survey of simulated LN cases for UK rheumatologists and nephrologists to identify treatment preferences for class IV and class V LN. Results Of 77 respondents, 48 (62.3%) were rheumatologists and 29 (37.7%) were nephrologists. A total of 37 (48.0%) reported having a joint clinic between nephrologists and rheumatologists, 54 (70.0%) reported having a multidisciplinary team meeting for LN and 26 (33.7%) reported having a specialized lupus nurse. Of the respondents, 58 (75%) reported arranging a renal biopsy before starting the treatment. A total of 20 (69%) of the nephrologists, but only 13 (27%) rheumatologists, reported having a formal departmental protocol for treating patients with LN (P  < 0.001). The first-choice treatment of class IV LN in pre-menopausal patients was MMF [41 (53.2%)], followed by CYC [15 (19.6%)], rituximab [RTX; 12 (12.5%)] or a combination of immunosuppressive drugs [9 (11.7%)] with differences between nephrologists' and rheumatologists' choices (P  = 0.026). For class V LN, MMF was the preferred initial treatment, irrespective of whether proteinuria was in the nephrotic range or not. RTX was the preferred second-line therapy for non-responders. Conclusion There was variation in the use of protocols, specialist clinic service provision, biopsies and primary and secondary treatment choices for LN reported by nephrologists and rheumatologists in the UK. [ABSTRACT FROM AUTHOR]