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Background:Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of Ikaros (IKZF1) and Aiolos (IKZF3), transcription factors involved in innate and adaptive immune cell development and homeostasis, and linked to the genetic risk for systemic lupus erythematosus (SLE). A phase 2, placebo-controlled study evaluated the efficacy and safety of iberdomide in patients (pts) with moderate to severe SLE.Objectives:To examine the effect of iberdomide on cutaneous manifestations in SLE pts.Methods:Adult autoantibody-positive SLE pts with a SLE Disease Activity Index 2000 (SLEDAI 2K) score ≥6 were randomized (2:2:1:2) to oral iberdomide (0.45, 0.3, 0.15 mg) or placebo once daily (QD) for 24 weeks while continuing standard background lupus medications. The Cutaneous Lupus Area and Severity Index Activity score (CLASI-A) was assessed every 4 weeks through week 24. As prespecified, exploratory analyses, change from baseline and the proportion of pts who achieved ≥50% reduction from baseline (CLASI-50) were evaluated for all pts, pts with baseline CLASI-A ≥8, and by cutaneous lupus subtypes (acute [ACLE], subacute [SCLE], chronic [CCLE]). CLASI-A outcomes were also evaluated post hoc for subgroups with high baseline expression of IKZF3 or the type 1 interferon (IFN) gene signatures in the blood.Results:Of 288 randomized pts, the mean and median (range) baseline CLASI-A scores were 6.9 and 5.0 (0-49), with 28% of pts having a score ≥8. 56% of pts had ACLE, 29% CCLE, and 16% SCLE. CLASI-50 responses were not significantly different comparing iberdomide to placebo in all pts and pts with baseline CLASI-A ≥8 at week 24, where high placebo response rates were observed (Table). Numerically greater mean improvement from baseline in CLASI-A scores in pts with baseline CLASI-A ≥8 was observed for iberdomide 0.45 mg vs placebo beginning at week 4, with continuous improvement through week 24. For pts with SCLE or CCLE, CLASI-50 response rates were significantly higher with iberdomide 0.45 mg vs placebo (PPIKZF3 or type 1 IFN gene signatures, with statistical significance achieved for SCLE pts but not CCLE pts (Figure).Table 1.CLASI-50 Response Rates by Subgroups at Week 240.15 mg QD0.3 mg QD0.45 mg QD(n=42)(n=82)(n=81)PlaceboSubgroup(n=83)0.15 mg QD vs Placebo0.3 mg QD vs Placebo0.45 mg QD vs Placebon/m (%)n/m (%)Str Diff in % (95% CI)P valuen/m (%)Str Diff in % (95% CI)P valuen/m (%)Str Diff in % (95% CI)P valueAll pts37/83 (44.6)19/42 (45.2)0.4 (-17.33, 18.55) P=0.96141/82 (50.0)5.3 (-9.93, 20.11) P=0.49945/81 (55.6)10.9 (-4.30, 25.51) P=0.163CLASI-A ≥810/20 (50.0)8/13 (61.5)15.9 (-17.42, 45.45) P=0.39913/24 (54.2)12.1 (-17.57, 39.97) P=0.45816/24 (66.7)15.1 (-15.51, 42.49) P=0.368ACLE23/50 (46.0)15/30 (50.0)4.8 (-17.22, 26.31) P=0.66220/43 (46.5)-3.3 (-22.95, 16.67) P=0.73817/38 (44.7)-3.0 (-23.20, 17.65) P=0.782SCLE9/17 (52.9)5/9 (55.6)2.6a (-33.04, 36.33) P=0.9663/9 (33.3)-6.6 (-38.98, 31.86) P>0.99911/12 (91.7)38.7a(4.54, 61.75) P=0.035CCLE5/18 (27.8)7/14 (50.0)22.2a (-10.51, 50.00) P=0.19810/23 (43.5)23.8 (-6.89, 48.88) P=0.12918/29 (62.1)34.1 (4.43, 56.16) P=0.029CI, confidence interval; Str Diff, stratified difference.aUnstratified difference.Conclusion:Iberdomide showed beneficial effects on skin manifestations in pts with SLE. Efficacy appears to be more pronounced in pts with SCLE and CCLE skin subtypes, and in pts with high IKZF3 or IFN gene expression signatures.Δ, treatment difference of adjusted means; CCLE, chronic cutaneous lupus erythematosus; CLASI-A, Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity score; IFN, interferon; SCLE, subacute cutaneous lupus erythematosus.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:Victoria Werth Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Joan Merrill Consultant of: UCB, GlaxoSmithKline, AbbVie, EMD Serono, Remegen, Celgene/Bristol Myers Squibb, AstraZeneca, Lilly, Immupharma, Amgen, Janssen, Resolve, Alpine, Aurinia, Astellas, Alexion, and Provention, Grant/research support from: GlaxoSmithKline and AstraZeneca, Richard Furie Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Thomas Dörner Consultant of: support for clinical studies and honoraria for scientific advice: AbbVie, Bristol Myers Squibb Company, Celgene, Eli Lilly, Janssen, Novartis, Roche, Employee of: Charite Universitätsmedizin, Berlin and DRFZ Berlin, Germany, Ronald van Vollenhoven Speakers bureau: UCB, AbbVie, Galapagos, Janssen, Pfizer, Paid instructor for: support for educational programs: Pfizer, Roche, Consultant of: AstraZeneca, Biogen, Biotest, Celgene, Gilead, Servier, UCB, AbbVie, Galapagos, Janssen, Pfizer, Grant/research support from: Bristol Myers Squibb, GlaxoSmithKline, Eli Lilly, UCB, Peter Lipsky Employee of: RILITE Foundation, Michael Weiswasser Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shimon Korish Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Peter Schafer Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Mark Stern Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Zhaohui Liu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shaojun Tang Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Nikolay Delev Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Background:Type I interferons and other inflammatory mediators derived from plasmacytoid dendritic cells (pDCs) are implicated in systemic lupus erythematous (SLE) pathology. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen 2 (BDCA2), a pDC-specific receptor. The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the surface of pDCs and subsequent inhibition of interferon, cytokine, and chemokine production. In Part A of the 2-part, phase 2 LILAC study (NCT02847598), BIIB059 significantly reduced SLE activity, as evidenced by reduced total active joint count (primary endpoint) and higher SLE Responder Index (SRI-4)1 response (a secondary endpoint) versus placebo.2Objectives:To evaluate SRI-4 response for BIIB059 versus placebo at Week 24 in SLE participant subgroups.Methods:Enrollment in LILAC Part A was open to adults fulfilling ≥ 4 of 11 revised 1997 ACR criteria for classification of SLE, with ≥ 4 tender and ≥ 4 swollen joints, active skin disease, and positive lupus antibodies. Participants were randomized to receive either BIIB059 450 mg or placebo subcutaneously every 4 weeks for 20 weeks (with an additional dose at Week 2). SRI-4 response at Week 24 was analyzed in subgroups, though analyses were limited by small sample sizes and were not powered for statistical testing.Results:In LILAC Part A, 64 and 56 participants were dosed with BIIB059 450 mg and placebo, respectively. At week 24, SRI-4 response rate was observed in favor of BIIB059 regardless of the baseline disease activity, such as SLEDAI-2K 2Conclusion:BIIB059 treatment was associated with greater SRI-4 response rate, consistent among different subgroups of baseline disease activity as measured by SLEDAI-2K and BILAG-2004, glucocorticoid dosage, and serology. These findings provide additional evidence of the potential benefit of BIIB059 for the treatment of patients with active SLE.References:[1]Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. 2. Furie RA, et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0935.Acknowledgements:This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen.Disclosure of Interests:Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Richard Furie Consultant of: Biogen, Grant/research support from: Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Consultant of: Biogen, Grant/research support from: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen

Background:Treatment with the type I interferon (IFN) receptor antibody anifrolumab was associated with clinical improvements in mucocutaneous and musculoskeletal disease activity in patients with systemic lupus erythematosus (SLE) in the phase 2 MUSE trial (NCT01438489) and phase 3 TULIP trials.1–4 Because rash and arthritis are the most common manifestations of SLE, the effect of anifrolumab on these symptoms can be examined in biomarker-defined subsets, as previously reported for the MUSE trial.2Objectives:To evaluate the effect of anifrolumab on rash and arthritis in patients with SLE, and the impact of IFN gene signature (IFNGS) on treatment response, using disease measures of different stringency in pooled data from the phase 3 TULIP trials.Methods:TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were placebo-controlled, 52-week trials of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE.3,4 In this post hoc analysis, outcomes of rash and arthritis were evaluated using mucocutaneous and musculoskeletal domains of the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) index. In addition, the modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) score was used to evaluate rash, and tender and swollen joint counts were used to assess arthritis.Results:360 patients received anifrolumab 300 mg (IFNGS test–high, n=298; IFNGS test–low, n=62) and 366 patients were given placebo (IFNGS test–high, n=302; IFNGS test–low, n=64). Change from baseline to Week 52 compared with placebo was measured by outcomes, ordered by their stringency. More anifrolumab-treated patients achieved rash improvement using SLEDAI-2K (complete resolution: difference 13.5%, nominal PP0: difference 15.6%, nominal PPPPP=0.029), BILAG severity lessening (difference 11.8%, nominal P=0.002), and ≥50% decrease in tender/swollen joint counts, when ≥6 at baseline (difference 12.6%, nominal P=0.016). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 11.7%, nominal P=0.005; BILAG: difference 12.9%, nominal P=0.003; joint counts: difference 11.3%, nominal P=0.054). In IFNGS test–low patients, there was a trend toward anifrolumab-associated arthritis improvement when measured using BILAG, and the effect of anifrolumab on the number of swollen/tender joint counts was similar to the IFNGS test–high group, although the IFNGS test–low sample size in this analysis was very small (Figure).Conclusion:In pooled data from the TULIP trials, anifrolumab treatment was associated with improvements in rash and arthritis using measures of different stringency. The SLEDAI-2K findings were largely driven by the subset of patients who were IFNGS test–high. However, using measures that were more sensitive to change, despite small sample sizes, IFNGS test–low patients may also have benefit.References:[1]Furie R, et al. Arthritis Rheumatol. 2017;69:376–86.[2]Merrill JT, et al. Lupus Sci Med. 2018;5:e000284.[3]Furie RA, et al. Lancet Rheumatol. 2019;1:e208–19.[4]Morand EF, et al. N Engl J Med. 2020;382:211–21.Acknowledgements:Writing assistance by Victoria Alikhan, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca.Disclosure of Interests:Joan T Merrill Consultant of: AstraZeneca, AbbVie, Amgen, Aurinia, BMS, EMD Serono, GSK, Remegen, Janssen, Provention, and UCB, Grant/research support from: BMS and GSK, Victoria Werth Speakers bureau: University of Pennsylvania, who own the copyright for the CLASI and SDASI, Consultant of: AbbVie, Amgen, Argenx, AstraZeneca, Biogen, BMS, Celgene, Chrysalis, CSL Behring, Cugene, Eli Lilly, EMD Serono, Genentech, GSK, Incyte, Idera, Janssen, Kirin, Medimmune, Medscape, Nektar, Octapharma, Pfizer, Principa, Regeneron, Resolve, and Viela Bio, Grant/research support from: AstraZeneca, Biogen, Celgene, Corbus Pharmaceuticals, Genentech, Gilead, Janssen, Pfizer, Syntimmune, and Viela Bio, Richard Furie Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, J Michelle Kahlenberg Consultant of: Admirex Pharmaceuticals, AstraZeneca, Aurinia Pharmaceuticals, BMS, Boehringer Ingelheim, Eli Lilly, and Ventus Therapeutics, Grant/research support from: BMS/Celgene and Q32 Bio, Gabriel Abreu Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

Background:Patients with cutaneous lupus erythematosus (CLE) experience symptoms including photosensitivity, rash, pain, and skin damage that can impact their quality of life. No targeted therapies are approved for CLE. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen-2 (BDCA2), expressed exclusively on the surface of plasmacytoid dendritic cells (pDCs). The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the cell surface of pDCs, thereby inhibiting the production of pDC-derived type I interferons, cytokines, and chemokines, which are involved in CLE pathology. In Part B of the 2-part, phase 2 LILAC study (NCT02847598), the primary endpoint was met: BIIB059 significantly reduced CLE activity, as evidenced by a statistically significant dose response and statistically significant differences in least-squares mean percent changes in Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity (CLASI-A) score1 versus placebo.2Objectives:To determine the proportion of patients with CLE who presented at baseline with moderate or severe disease (CLASI-A ≥ 10) or with the higher category of mild disease (CLASI-A < 10 [i.e., 8 or 9]) and experienced a shift in CLASI-A score to a mild skin disease category or clear/almost clear skin status.Methods:Adults with histologically confirmed CLE with or without systemic manifestations were enrolled if they had CLASI-A ≥ 8 at baseline, despite prior use of or intolerance to topical corticosteroids (CS) and/or antimalarials, in addition to ≥ 1 lesion diagnostic of subacute CLE (CLASI-A erythema score ≥ 2) and/or chronic CLE (CLASI-A erythema score ≥ 2 and CLASI-Damage scarring score ≥1). Concomitant CLE/SLE therapy was allowed if doses were initiated ≥ 12 weeks and kept stable ≥ 4 weeks before randomization and throughout the treatment period. Systemic corticosteroid doses could not exceed 15 mg/day of prednisone (or equivalent). BIIB059 (50, 150, 450 mg) or placebo was subcutaneously administered once every 4 weeks for 12 weeks, with an additional dose at Week 2. An ad hoc analysis was conducted to determine the proportion of participants (CLASI-A ≥ 10 or < 10 at baseline) with a shift in CLASI-A score to ≤ 1, ≤ 3, ≤ 6, and ≤ 8 at Week 16.Results:In this ad hoc analysis from LILAC Part B, 106 (80.3%) and 26 (19.7%) of participants had a baseline CLASI-A score ≥ 10 and < 10, respectively. Compared with placebo, higher proportions of participants treated with BIIB059 achieved a shift in CLASI-A score from either ≥ 10 or < 10 at baseline to ≤ 1, ≤ 3, ≤ 6, and ≤ 8 at Week 16 (Figure 1). Treatment with BIIB059 resulted in higher proportions of participants achieving reduced scores, indicating shifts to more mild disease activity, compared with placebo. A score ≤ 1 (clear or almost clear skin) at Week 16 was achieved by 0.0% (0/25), 5.0% (1/20), 14.3% (3/21), and 12.5% (5/40) of participants with baseline CLASI-A ≥ 10 who were treated with placebo and BIIB059 50, 150, and 450 mg, respectively. Two of 26 participants with baseline CLASI-A < 10 achieved a score ≤ 1 (both received BIIB059 150 mg).Conclusion:A greater proportion of participants achieved milder skin disease or clear/almost clear skin status in the BIIB059 groups as compared with the placebo group. This effect was observed in participants with moderate or severe disease as well as in those in the higher range of the mild category of disease severity at baseline, indicating the ability of BIIB059 to improve skin lesions in patients with a broad range of cutaneous disease activity.References:[1]Albrecht J, et al. J Invest Dermatol. 2005;125(5):889-894.[2]Werth V, et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0986.Acknowledgements:This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was from Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen.Disclosure of Interests:Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Richard Furie Consultant of: AstraZeneca, Biogen, Grant/research support from: AstraZeneca, Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Consultant of: Biogen, Filippa Nyberg Consultant of: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Michael Tee Speakers bureau: Pfizer, Novartis, Johnson & Johnson, Celltrion, Consultant of: Neovacs, Grant/research support from: Celltrion, Johnson & Johnson, Pfizer, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen

ObjectivesTreat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.

Background:CLE represents an unmet medical need with no approved therapy. BIIB059, a humanized monoclonal antibody, binds to BDCA2 and inhibits pro-inflammatory mediators production, including type I interferons. BIIB059 was evaluated in Phase 1 studiesNCT02106897andNCT03224793. LILAC is a 2-part Phase 2 study: Part A enrolled SLE pts; Part B enrolled pts with active CLE (NCT02847598).Objectives:Evaluate efficacy and safety of BIIB059 in pts enrolled in Part B at Week 16, end of treatment (EOT) period.Methods:Pts with active CLE, SCLE and/or CCLE and adjudicated Cutaneous Lupus Disease Area and Severity Index – Activity (CLASI-A) ≥8 were enrolled and randomized to receive either BIIB059 (50, 150 or 450 mg) or placebo (PBO) s.c. Q4W. Primary endpoint was dose response defined by % change in CLASI-A score from baseline (BL) to Week 16. Secondary endpoints included CLASI-50 response rate and ≥ 7-point reduction in CLASI-A score from baseline to EOT. Adverse events and serious adverse events were recorded throughout the study.Results:132 pts with active CLE were randomized. The study met its primary endpoint, demonstrating a dose response (p= 0.0005) and a statistically significant difference in % change from BL in CLASI-A score in BIIB059-treated pts vs PBO. Table 1 and Table 2 summarize efficacy and safety results, respectively.Table 1.Efficacy EndpointsBIIB059PBO50 mg150 mg450 mgLS Mean (SE)LS Mean (SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.Primary EndpointCLASI-A % change from BL-14.5 (6.4)-40.8 (7.5)-26.3 (-45.7; -7.0)0.008-47.9 (7.4)-33.5 (-52.7; -14.3)0.001-43.5 (5.5)-28.0 (-44.5; -11.5)0.001Secondary Endpointsn(%)n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.Prop. of participants achieving CLASI 507/32 (21.9%)10/26 (38.5%)15.8% (-7; 39)0.13311/25 (44.0%)21 (-2.8; 45)0.05920/43 (46.5%)23 (3; 44)0.024Prop. of participants achieving a ≥7-point CLASI-A reduction from BL7/32 (21.9%)9/26 (34.6%)12.3 (-11.3; 35.8)0.22812/25 (48.0%)22.2 (-2.0; 46.3)0.05518/43 (41.8%)16.8 (-6.7; 40.4)0.048*LSMD=LS Mean DifferencePBOBIIB059OVERALLN=3350 mgN=26150 mgN=25450 mgN=48PooledN=99N=132Any Event, n(%)18 (54.5)17 (65.4)12 (48)33 (68.8)62 (62.6)80 (60.6)SeverityMild11 (33.3)11 (42.3)8 (32.0)19 (39.6)38 (38.4)49 (37.1)Moderate4 (12.1)6 (23.1)3 (12.0)12 (25.0)21 (21.2)25 (18.9)Severe3 (9.1)01 (4.0)2 (4.2)3 (3.0)6 (4.5)Related events6 (18.2)9 (34.6)4 (16.0)16 (33.3)29 (29.3)35 (26.5)Serious events2 (6.1)03 (12.0)2 (4.2)5 (5.1)7 (5.3)Related serious events1 (3.0)01 (4.0)1 (2.1)2 (2.0)3 (2.3)Events leading to drug withdrawal01 (3.8)1 (4.0)1 (2.1)3 (3.0)3 (2.3)Events leading to study withdrawal0001 (2.1)1 (1.0)1 (0.8)Fatal events000000Conclusion:BIIB059 administration to pts with active CLE resulted in statistically significant dose-related improvement in disease activity vs PBO with no untoward safety signals. Further development of BIIB059 in CLE is warranted.Disclosure of Interests:Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Juanita Romero-Diaz Consultant of: Biogen, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson & Johnson, Abbvie, Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Filippa Nyberg Consultant of: Biogen, Benjamin Kaffenberger Grant/research support from: Amgen, Biogen, InflaRx, Veloce Biopharmaceuticals, Dermatology Foundation, Saira Sheikh: None declared, Goran Radunovic: None declared, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Francois Gaudreault Shareholder of: Biogen, Employee of: Biogen, Adam Meyers Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, Employee of: Biogen

Background:Lenabasum is a synthetic, non-immunosuppressive, selective cannabinoid receptor type 2 agonist that activates resolution of inflammation. Lenabasum had acceptable safety and tolerability and improved efficacy outcomes in the initial 16-week double-blinded, randomized, placebo-controlled Part A of Phase 2 trial JBT101-DM-001 (NCT02466243) in DM subjects with refractory skin involvement. In that study, lenabasum or placebo was added to stable background treatment, with immunosuppressive therapies allowed.Objectives:To assess long-term safety and efficacy in DM subjects in this study.Methods:Subjects who completed Part A of the Phase 2 study (n = 22) were eligible to receive oral lenabasum 20 mg BID in an open-label extension (OLE) that assessed safety and efficacy at 4 weeks, then every 8 weeks.Results:20/22 (91%) eligible subjects enrolled in the OLE, following a mean interval of 31 weeks from the end of Part A, during which they continued to receive standard-of care treatments, to the start of the OLE during which lenabasum 20 mg BID was added. 17/20 (85%) subjects were on stable baseline immunosuppressive drugs. At the time of this data cut-off, 17 subjects were still enrolled, 17 had completed 140 months (2.7 years), and 15 had completed 156 months (3 years) of OLE dosing.All OLE subjects experienced at least 1 adverse event (AE), with 118 AEs during the OLE through Dec 2020. Most AEs were mild (n = 111, 94%), with 2 severe AEs (fatigue and metastatic prostate cancer) considered unrelated to lenabasum. AEs occurring in ≥ 3/20 OLE subjects were: URI (n = 5); fatigue (n = 4); nausea (n = 3); common cold (n = 3); UTI (n = 3); and DM flare (n = 3). No serious AEs related to lenabasum have been reported in this OLE to date. No subject discontinued the OLE because of an AE related to lenabasum.Improvement was seen in multiple physician- and patient-reported efficacy outcomes. CDASI activity score improved through the first 15 months of lenabasum treatment in the OLE and remained stable thereafter, with an improvement of ~20 points from the beginning of the study maintained from Month 15 through Year 3 in the OLE. CDASI damage score increased through the first year of the OLE, even though skin activity was decreasing, but lessened thereafter, returning after 3 years to about the same level it was at the beginning of the OLE. Other outcomes shown in Figure 1 followed the same general pattern as CDASI activity score, with improvement through the first 12-16 months of the OLE, then stability thereafter. Of note, 2 subjects had disease flares shortly after stopping lenabasum for conclusion of the OLE.Conclusion:Lenabasum continues to have a favorable safety and tolerability profile in the OLE of the Phase 2 trial JBT101-DM-001 with no serious AEs or study discontinuations related to lenabasum. The CDASI activity score and multiple other physician and patient-reported outcomes improved and have remained stable, showing durability of improvement in these patients with refractory skin disease. Skin damage was reversible and began to improve once skin activity stabilized. The limitations of attributing this improvement to lenabasum in the setting of open-label dosing is acknowledged. These data support further testing of lenabasum for the treatment of DM, and a Phase 3 study of lenabasum in DM is ongoing.Figure 1.Change from Baseline in Selected Efficacy Outcomes in OLE of Phase 2 Trial JBT101-DM-001Disclosure of Interests:Victoria Werth Grant/research support from: Investigator for Corbus Pharmaceuticals and received funding to conduct trials, Josef Concha: None declared, Julie Burroughs: None declared, Joyce Okawa: None declared, Rui Feng: None declared, Anisha Jobanputra: None declared, Robert Borucki: None declared, Kathleen Hally Employee of: Employee of Corbus Pharmaceuticals, Emily Hejazi: None declared, Michael Tillinger Employee of: Employee of Corbus Pharmaceuticals, Scott Constantine Employee of: Employee of Corbus Pharmaceuticals, Nancy Dgetluck Employee of: Employee of Corbus Pharmaceuticals, Barbara White Employee of: Employee and stockholder of Corbus Pharmaceuticals

ObjectiveTo develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.MethodsCandidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria.ResultsBased on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of ConclusionsThe European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

We have with interest read the ‘Correspondence on “EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups” by Irfan et al ’ with subtitle: improving the subtyping of dermatomyositis in the 2017 EULAR/ACR classification criteria for juvenile and adult idiopathic inflammatory myositis: value of non-classic cutaneous findings, to be published in Annals of the Rheumatic Diseases .1 Here, the authors present performance of the EULAR/ACR classification criteria2 in a cohort from India of 26 consecutive adult patients with idiopathic inflammatory myopathies (IIM). Patients with characteristic skin rashes (those included in the EULAR/ACR criteria as well as in the older Bohan and Peter criteria) were classified as having dermatomyositis (DM). The remainder of the patients were classified as polymyositis (PM) (n=12). All patients had documented muscle weakness. Of the 12 patients classified as PM, seven had non-classical skin rash such as generalised erythematous rash or malar rash and had been given the diagnosis DM by their physician. Moreover, five of these seven patients had myositis-associated autoantibodies that largely supported the clinical diagnosis of DM. The authors conclude that the sensitivities of Gottron’s papules (60%–80%) and heliotrope rash (30%) are low. The authors suggest …

Background:In a Phase 2 study, Ustekinumab (UST) showed improvement at week (wk) 24 in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) response (≥4-point improvement from baseline [BL]) vs placebo (PBO).1Post hoc analysis revealed that more patients (pts) on UST vs PBO achieved ≥50% improvement in total CLASI activity score.Objectives:To examine the relationships of CLASI activity responses to SLEDAI-2K (S2K) mucocutaneous disease responses.Methods:Adults with SLE (S2K ≥6, ≥1 BILAG A and/or ≥2 BILAG B scores) despite standard of care (SOC) therapy were enrolled. Pts (n=102) were randomized (3:2) to UST ~6 mg/kg IV or PBO at wk 0, followed by UST 90 mg SC or PBO every 8 wks beginning at wk 8 + SOC. S2K index measures complete improvement from BL; S2K Responder Index-50 (S2K RI-50) evaluates partial improvement (≥50%) in S2K rash. CLASI rash: sum of erythema and scale/hypertrophy score. In post hoc analysis, improvement in CLASI activity score at wk 24 was calculated using increasing thresholds of BL disease activity and various cut points of improvement to define treatment response.Results:Complete improvement from BL in rash was concordant between CLASI and S2K (correlation coefficients [r] ≥0.997, Table 1). There was less agreement between CLASI and S2K RI-50 for assessing partial improvement in rash. Treatment difference (UST vs PBO) in % pts achieving partial improvement in rash was observed for CLASI (60% vs 38.5%), but not S2K RI-50 (51.1% vs 50%). Complete improvement from BL in mucosal ulceration was congruent between CLASI and S2K (r=1). Both instruments demonstrated greater proportions of responders to UST vs PBO. Treatment differences between UST and PBO in achieving ≥20%, ≥35%, and ≥50% improvement from BL in total CLASI activity score were noteworthy at various thresholds of disease activity (Table 2).Table 1.CLASI Activity Scores vs SLEDAI-2K Activity24-Week ImprovementTreatmentActivity Measure% (n/N*)r**CLASI RashSLEDAI-2K Rash100%PBO30.8 (8/26)30.8 (8/26)1.0000UST28.9 (13/45)31.1 (14/45)0.9997≥50%PBO38.5 (10/26)50.0 (13/26)0.9996UST60.0 (27/45)51.1 (23/45)0.8693CLASIMucosal UlcerSLEDAI-2KMucosal Ulcer100%PBO66.7 (8/12)69.2 (9/13)1.0000UST89.5 (17/19)89.5 (17/19)1.0000*N=Evaluated pts with BL SLEDAI rash present, total CLASI activity score >0, and CLASI rash or mucosal ulcer activity scores >0 in analyses of subcomponents; **Calculated using tetrachoric correlation.Table 2.Differences in Partial Improvement in Total CLASI Activity Score at Various BL Disease Activity ThresholdsCLASI Total Activity ScoreImprovementThreshold (%)PBO% (n/N*)UST% (n/N*)Difference % (UST vs PBO)BL >0≥2054.8 (17/31)74.5 (38/51)19.7≥3541.9 (13/31)60.8 (31/51)18.9≥5041.9 (13/31)54.9 (28/51)13.0BL ≥4≥2058.8 (10/17)71.9 (23/32)13.1≥3535.3 (6/17)62.5 (20/32)27.2≥5035.3 (6/17)53.1 (17/32)17.8BL ≥6≥2053.8 (7/13)72.0 (18/25)18.2≥3530.8 (4/13)60.0 (15/25)29.2≥5030.8 (4/13)52.0 (13/25)21.2BL ≥8≥2058.3 (7/12)70.6 (12/17)12.3≥3533.3 (4/12)58.8 (10/17)25.5≥5033.3 (4/12)47.1 (8/17)13.8*N=Evaluated pts with BL total CLASI activity score >0, ≥4, ≥6, ≥8 based on post hoc analysesConclusion:CLASI demonstrated partial improvement in active mucocutaneous disease that was not captured by S2K RI-50. Treatment effect favoring UST vs PBO was observed across range of thresholds of BL CLASI activity and cut points used to define improvement, which have previously been shown to be clinically meaningful.2Findings are based on a limited sample size and treatment duration; results will be confirmed in an ongoing Phase 3 UST trial (NCT03517722).References:[1]Van Vollenhoven R.Lancet. 2018;392:1330[2]Chakka S.JID.2019;139: S101 (#587)Disclosure of Interests:Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Bevra H. Hahn Grant/research support from: Janssen Research & Development, LLC, George Tsokos Grant/research support from: Janssen Research & Development, LLC, Shawn Rose Employee of: Janssen Research & Development, LLC, Kaiyin Fei Employee of: Janssen Research & Development, LLC, Y Irene Gregan Employee of: Janssen Research & Development, LLC, Robert Gordon Employee of: Janssen Research & Development, LLC, Kim Hung Lo Employee of: Janssen Research & Development, LLC, Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Janssen Research & Development, LLC, Lilly, Pfizer, Roche, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB and Vertex, Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Vertex

Background:The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus initiative to identify, prioritize and address top barriers in lupus drug development, clinical care and access to care. The Lupus Foundation of America convenes ALPHA with Tufts Center for the Study of Drug Development and a Global Advisory Committee of lupus experts representing clinician-scientists, industry and patients.Objectives:Collect global patient input to determine alignment with the lupus clinician-scientist community on prior published consensus of top lupus barriers.Methods:A 23-question online Qualtrics survey was developed to identify challenges across lupus diagnosis, clinical care and research participation. The survey, available in English, Spanish, Korean and simplified Chinese, was fielded in November 2019 to people with lupus and caregivers of children Results:Analysis included only consented responses with ≥ 68% survey completion (n=3,447) received across 83 countries. 95% were female with a mean age of 45. Respondents reported being White (57%), Black or of African descent (14%), Hispanic or Latino (18%) and Asian (10%). 65% resided in the US while 35% resided in countries outside of the US. 97% were people with lupus while 3% were caregivers to children Highest ranked challenges were similar globally and across children and adults: medication side effects, lack of treatment options and high out-of-pocket costs. Managing side effects ranked significantly higher (pConclusion:This global survey revealed that medication side effects and lack of effective treatments are top challenges for people with lupus, including children. Most respondents were never asked by their doctors to participate in a clinical trial, which may explain difficulties in trial recruitment. These barriers are consistent with prior published barriers identified by the clinician-scientist community.Acknowledgments:ALPHA sponsors: EMD Serono, GSK, Aurinia, MallinckrodtDisclosure of Interests:Karin Tse: None declared, Yaritza Peña: None declared, Kathleen Arntsen: None declared, Sang-Cheol Bae: None declared, Lauren Bloch Consultant of: Faegre Drinker Consulting is a division of Faegre Drinker Biddle & Reath, a law and consulting firm that represents patient advocacy organizations and sponsors developing drugs, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB, Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca, Bradley Dickerson Employee of: Aurinia, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen, Kenneth Getz: None declared, Amy Kao Employee of: EMD Serono, Susan Manzi: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Sandra Raymond: None declared, Brad H Rovin Grant/research support from: GSK, Consultant of: GSK, Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Joan Von Feldt Shareholder of: GSK, Employee of: GSK, David Zook Consultant of: Faegre Drinker Consulting is a division of Faegre Drinker Biddle & Reath, a law and consulting firm that represents patient advocacy organizations and sponsors developing drugs, Leslie Hanrahan: None declared

We have read with great interest the article by Kato and colleagues regarding the ‘Apoptosis-derived membrane vesicles drive the cGAS–STING pathway and enhance type I IFN production in systemic lupus erythematosus’.1 However, we are concerned that the authors studied exclusively blood serum, that is, all blood samples from their patients with lupus and healthy controls were coagulated ex vivo before analysis. At least three major changes can occur to the population of membrane microvesicles (MVs) during coagulation in a test tube. First, a subset of circulating MVs participate in, and become consumed by, clotting. For example, studies from our group and others indicated that over half of the total membrane MVs in blood plasma …

Background The effect of pregnancy on Dermatomyositis (DM) disease activity and on maternal and fetal outcomes in patients with DM is unclear1,2. Objectives Evaluate disease activity and pregnancy outcomes complicated by maternal dermatomyositis. Methods A total of 10 patients with 21 pregnancies from a cohort of 438 DM patients of child-bearing potential, diagnosed between 2006 and 2015 from two centers, were eligible for interview with a specific questionnaire regarding pregnancy and fetal outcomes. Results Weakness, rash and arthritis were the most common clinical symptoms that improved during pregnancy in affected patients (Figure 1). In 16 out of 18 pregnancies, patients experienced weakness. Weakness improved during 13 pregnancies (81.3%), stayed the same during 2 pregnancies (12.5%), and worsened during one (6.3%). All 10 patients experienced cutaneous rash during all 18 pregnancies carried to live birth. Cutaneous rash improved during 13 pregnancies (72.2%), remain unchanged during 3 (16.7%), and worsened during 2 (11.1%). Five patients experienced arthralgias or arthritis in a total of 11 pregnancies. Symptoms improved during 10 of these pregnancies (91%) and worsened during one (9%).There were no cases of interstitial lung disease, cancer or antiphospholipid antibody syndrome among the 10 patients studied. One patient suffered from pre-eclampsia while diagnosed with DM. 3 total pregnancy losses: two early miscarriages ( Conclusions Pregnancy does not appear to carry a worse prognosis for DM patients and all but one of our patients experienced improvement in clinical symptoms during pregnancy. References Iago PF et al. Pregnancy in adult-onset idiopathic inflammatory myopathy: Report from a cohort of myositis patients from a single center. Semin Arthritis Rheum, 2014. 44 (2):p.234–240. Oddis, C.V., et al., Incidence of polymyositis-dermatomyositis: a 20-year study of hospital diagnosed cases in Allegheny County, PA 1963–1982. J Rheumatol, 1990. 17(10): p. 1329–34. Disclosure of Interest None declared

Background Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by an auto-inflammatory immune response in muscle and skin. Multiple lines of evidence suggest Toll-like receptors (TLRs), central components of the innate immune system, play a key role in DM pathogenesis. A retrospective study evaluating muscle biopsy samples showed that TLR9, TLR4 and TLR2 were significantly over-expressed in skeletal muscle and infiltrating cells in DM subjects compared to controls. Over-expression of type I and type II interferons and other cytokines has been demonstrated in DM, suggesting involvement of the NF-κβ pathway. Expression of certain cytokines also had significant positive correlations with expression of TLR9 and TLR4. IMO-8400 is an investigational oligonucleotide-based antagonist of TLRs 7, 8 and 9 that has demonstrated clinical activity in patients with psoriasis. We hypothesize that inhibition of TLR activity in patients with DM with IMO-8400 has the potential to reduce chronic inflammation in affected tissue. Objectives Our objective was to design a Phase 2 clinical trial of IMO-8400 in DM patients using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) as the primary efficacy endpoint. Specifically, we wished to estimate the placebo response for the CDASI and calculate optimal treatment effect in order to estimate optimal subject numbers and length of trial. Methods Retrospective analyses were conducted using longitudinal CDASI assessments for 115 unique DM patients seen at the Stanford University outpatient dermatology clinic. Patients with multiple assessments approximately 12 or 24 weeks apart were grouped by the first visit CDASI activity score ( Results Over 24 weeks, a 5 point or greater decrease in CDASI activity score was observed at 31.8% of patient visits, with the change in CDASI activity score ranging from -23 to +27 points across all patients. Because some patients experienced clinically meaningful changes of 4 to 5 points on the CDASI following treatment with standard of care therapies, a 7 point treatment effect was targeted for the IMO-8400 trial. Sample size calculations resulted in 10 patients per treatment group, assuming a standard deviation of 8.5 points over 24 weeks using a Repeated Measures Mixed Model analysis of change from baseline on monthly CDASI assessments (>80% power on a 1-sided test; alpha=0.05). Conclusions Based on these analyses, we initiated a double-blind, placebo-controlled, 24-week Phase 2 clinical trial in DM patients (NCT number: NCT02612857). Key entry criteria include adults with DM aged 18–75 years, CDASI activity score ≥15, clinical symptoms of active muscle disease, and abnormal serum CK or ALD, EMG, muscle biopsy or MRI. Additional outcome measures include MMT-8, timed function tests including 10-meter run walk, and exploratory biomarkers of disease activity. Disclosure of Interest P. Gordon Grant/research support from: Idera Pharmaceuticals, Inc., R. Cooper Grant/research support from: Idera Pharmaceuticals, Inc., H. Chinoy Grant/research support from: Idera Pharmaceuticals, Inc., D. Isenberg Consultant for: Idera Pharmaceuticals, Inc., I. Lundberg Consultant for: Idera Pharmaceuticals, Inc., V. Werth Consultant for: Idera Pharmaceuticals, Inc., K. Gruis Employee of: Idera Pharmaceuticals, Inc., M. Hurtt Employee of: Idera Pharmaceuticals, Inc., J. Brevard Employee of: Idera Pharmaceuticals, Inc., L. Granlund Employee of: Idera Pharmaceuticals, Inc., D. Fiorentino Grant/research support from: Idera Pharmaceuticals, Inc., Consultant for: Idera Pharmaceuticals, Inc.

Background Increased activity of the type I interferon (IFN) pathway is central to the pathogenesis of SLE. Blocking the type I receptor may reduce SLE activity more effectively than inhibiting IFN-α alone. Objectives Efficacy and safety of anifrolumab were assessed in a Phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate to severe SLE (the MUSE study). Methods 305 patients were treated for 48 weeks with intravenous anifrolumab (300 mg or 1000 mg) or placebo, in addition to standard-of-care medications. Randomization was stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) score ( Results The primary endpoint was met by more anifrolumab-treated patients [placebo vs. 300 mg vs. 1000 mg: 17.6%, 34.3% ( p =0.014), 28.8% ( p =0.063)] with greater effect sizes observed in the 75% of patients who had a high baseline IFN signature [13.2%, 36.0% ( p =0.004), 28.2% ( p =0.029)]. At Day 365 more anifrolumab-treated patients achieved SRI(4) responses [40.2%, 62.6%, ( p p =0.043)], BILAG-based Composite Lupus Assessment (BICLA) [25.7%, 53.5% ( p p =0.018)], modified SRI(6) [28.4%, 49.5% ( p =0.002), 44.7% ( p =0.015)], and SLEDAI-2K ≤2 [17.6%, 35.4% ( p =0.004), 32.7% ( p =0.012)]. Major clinical response (BILAG “C” or better in all domains at Day 169 maintained to Day 365) was achieved by 6.9%, 19.2% ( p =0.012), and 17.3% ( p =0.025) of patients. BILAG “A” flares were reported in more placebo- vs. anifrolumab-treated patients (16.7%, 9.1%, 10.6%). In patients with baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score ≥10, more anifrolumab-treated patients attained a ≥50% reduction by Day 365 [30.8%, 63.0% ( p =0.013), 58.3% ( p =0.077)]. In patients with ≥8 swollen and ≥8 tender joints at baseline more anifrolumab-treated patients achieved ≥50% decrease in joint count [48.6%, 69.6% ( p =0.038), 64.6% ( p =0.156)]. Although steroid tapering was not mandated, OCS reduction to ≤7.5 mg/d at Day 365 was achieved by 26.6%, 56.4%, and 31.7% of patients. The observed benefits were driven by results in the IFN-high subpopulation (figure). Median suppression of 21 IFN-regulated genes was ∼90% for both doses of anifrolumab. Patients in the placebo group had the lowest incidence of Herpes zoster (2.0%, 5.1%, 9.5%) and cases reported as influenza (2.0%, 6.1%, 7.6%); there were no differences in the incidence of serious adverse events (18.8%, 16.2%, 17.1%). The incidence of infusion-related reactions was similar (5.9%, 2.0%, 3.8%). Conclusions Anifrolumab significantly reduced disease activity across all clinical endpoints. Enhanced effects in IFN-high patients support the pathobiology of this treatment strategy. Acknowledgement Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK Disclosure of Interest R. Furie Consultant for: MedImmune, J. Merrill Grant/research support from: MedImmune; Genentech/Roche, Consultant for: Medimmune, Genentech/Roche, Neovacs, V. Werth Consultant for: MedImmune, M. Khamashta: None declared, K. Kalunian Grant/research support from: MedImmune, Consultant for: AstraZeneca, P. Brohawn Shareholder of: AstraZeneca, Employee of: MedImmune, G. Illei Shareholder of: AstraZeneca, Employee of: MedImmune, J. Drappa Shareholder of: AstraZeneca, Employee of: MedImmune, L. Wang Employee of: MedImmune, S. Yoo Shareholder of: AstraZeneca; Regenx Bio, Consultant for: Regenx Bio

Background Treat-to-target recommendations identified “remission” as a target in SLE but recognize that there is no generally accepted definition for remission in this disease. Objectives To achieve consensus, in a large multi-party international panel, on potential definitions for remission in SLE. Methods An international expert panel of sixty rheumatologists, nephrologists, dermatologists, clinical immunologists, and patient representatives participated in preparatory exercises, a full-day face-to-face meeting, and follow-up exercises and electronic voting rounds. Results Eight key statements regarding remission in SLE achieved >90% agreement (table). There were different viewpoints on the required duration of remission. In addition, the panel expressed strong support (>90%) for the following principles which will guide the further development of remission definitions: I. A definition of remission in SLE will be worded as follows: Remission in SLE is a durable state characterized by [a definition of: absence of symptoms, signs, abnormal labs, (serology)] Ia. Remission-off-therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials. Ib. Remission-on-therapy allows patients to be treated with maintenance antimalarials, stable, low-dose steroids (prednisone ≤5 mg/d), maintenance immunosuppressives and/or stable (maintenance) biologics. II. Assessment of clinical symptoms and signs should be based on a validated index, e.g., clinical-SLEDAI =0, BILAG D/E only, clinical ECLAM =0; supplemented with PhysGA III. For testing the construct validity of each potential remission definition the most appropriate outcomes (dependent variables) are: Death, Damage, Flares, and HR-QOL measures. Conclusions The work of this international consensus panel provides a framework for testing individual definitions of remission against longer-term outcomes. Disclosure of Interest R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, C. Aranow: None declared, G. Bertsias: None declared, E. Bonfa: None declared, R. Cervera: None declared, N. Costedoat-Chalumeau: None declared, T. Dorner: None declared, F. Houssiau: None declared, K. Lerstrom: None declared, E. Morand: None declared, M. Mosca: None declared, S. Navarra: None declared, M. Petri: None declared, M. Urowitz: None declared, A. Voskuijl: None declared, A. Voss: None declared, M. Ward: None declared, V. Werth: None declared, M. Schneider: None declared

Background Inadequate classification criteria for IIM are a fundamental limitation in clinical studies. An international, multidisciplinary collaboration, the International Myositis Classification Criteria Project (IMCCP), supported by ACR and EULAR, was established to address this problem. Objectives Develop and validate new classification criteria for adult and juvenile IIM and its major subgroups. Methods Candidate variables were selected from published criteria and inclusion criteria in controlled trials of myositis. Comparator conditions confused with IIM were defined. Clinical and laboratory data from IIM and comparator patients were collected from 47 rheumatology, dermatology, neurology and pediatrics clinics worldwide from 2008-2011. Crude pair-wise associations among all measured variables and between each variable and clinicians’ diagnoses were assessed. The explored approaches were: Traditional: case defined by specified number of items from a set of variables Probability score: case assigned a probability score by summing score-points associated with a set of variables Classification tree: case defined by a decision tree Internal validation using bootstrap methods was performed. Results Data from 973 IIM patients (74% adults; 26% children), representing subgroups of IIM, and 629 comparators (81% adults; 19% children) were obtained. Two probability score models were developed: Model 1 comprised clinical variables on muscles, skin, and laboratory measures; Model 2 additionally comprised muscle biopsy variables. Model 1 performed nearly as well as Model 2 (specificity 87% vs. 88%, sensitivity 89% vs. 89%, and correctly classified 87% vs. 89%). Both models performed as well as, and often better than, the classification tree that was developed (sensitivity 88%, specificity 72%, and correctly classified 84%) and published criteria. Conclusions New classification criteria for IIM with readily clinically assessable measurements and symptoms have been developed. They generally show superior performance compared with existing criteria. External validation is in progress. Disclosure of Interest None Declared

Background Dermatomyositis (DM) is a subset of idiopathic inflammatory myopathies (IIM), which are heterogeneous rheumatic disorders characterized by inflammation of skeletal muscle and progressive weakness. New and improved treatment is needed but a significant and fundamental problem for conducting clinical trials is the inadequate classification criteria for IIM. To address this, the International Myositis Classification Criteria Project (IMCCP) was established with the aim to develop and validate new classification criteria for IIM and major subgroups of IIM. Clinical and laboratory data from 1600 IIM and comparator cases have been collected. Dissimilarities in disease manifestations among different patient groups have to be considered as classification criteria must be uniformly valid. Little, however, is known about these differences in relation to clinical phenotype for IIM. Objectives The aim of this study was to investigate ethnic or gender differences in clinical manifestations in adult DM, juvenile DM (JDM) and amyopathic DM (ADM). Methods We extracted data on serology, 23 muscle variables (e.g., pattern of muscle weakness) and 14 skin manifestations from the IMCCP database and assessed their prevalence among 238 DM, 233 JDM and 45 ADM patients. Comparisons were made between genders and patients of Caucasian and Asian origin. Results Comparisons between the two ethnic groups revealed significant differences in clinical phenotypes. For adult DM cases, several muscle variables were more prevalent among Caucasians compared to Asians with neck flexor weakness (p