Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study

OBJECTIVE:To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG).METHODS:The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The co-primary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to either a two-cycle rituximab/placebo regimen, with follow-up through 52-weeks.RESULTS:Of the 52 participants included, mean (±SD) age at enrollment was 55.1 (±17.1) years; 23 (44.2%) were female, and 31 (59.6%) were MGFA Class II. The mean (±SD) baseline prednisone dose was 22.1 (±9.7) mg/day. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs. 56% on placebo. The study reached its futility endpoint (p=0.03) suggesting that the pre-defined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues identified.CONCLUSIONS:While rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase-3 trial of mild-moderately symptomatic AChR-Ab+ gMG.CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for mild-to-moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year.TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02110706

December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

No abstract available. Article truncated after 150 words. History of Present Illness A 56-year-old man was referred for a second opinion on recent onset of diffuse parenchymal lung disease. He had started noting mild dyspnea with yard work approximately in March 2021. His symptoms progressed over the next month with increasing shortness of breath and some fever. He presented to outside emergency department on April 17, 2021 and chest CT showing patchy ground-glass opacities with some areas of irregular consolidation (Figure 1). He was subsequently seen by an outside pulmonologist and started empirically on prednisone (50 mg/day). An outside lung biopsy had been performed which showed nonspecific interstitial pneumonitis. There was some improvement in his symptoms and his prednisone dose was reduced to 20 mg/day; however, his symptoms subsequently worsened with saturations noted to drop to 85% with any ambulation. He also had swelling of his left face and a biopsy of the parotid gland with the findings …

LLDAS is an attainable treat-to-target goal in childhood-onset SLE

ObjectivesTo study whether clinical remission (CR) and Low Lupus Disease Activity State (LLDAS) are achievable goals in childhood-onset SLE.MethodsData on medication use and disease activity were prospectively collected. LLDAS was defined as Safety of Estrogen in Lupus Erythematosus National Assesment-SLE disease Activity Index (SELENA-SLEDAI) ≤4 with zero scores for renal, Central Nervous System (CNS), serositis, vasculitis and constitutional components, no increase in any SLEDAI component since the previous visit, PGA ≤1, and prednisone dose ≤7.5 mg/day. CR on treatment (Tx) was defined as a Physician Global Assessment <0.5, SELENA-SLEDAI=0, with prednisone ≤5 mg/day and maintenance treatment with immunosuppressives. CR off Tx was the same but without prednisone or other immunosuppressive usage.Results51 patients (700 visits) were included. Within 3 months after diagnosis, 94.1% of children were treated with hydroxychloroquine and 60.8% with prednisone. Prednisone dosage decreased from a median of 0.74 mg/kg/day at diagnosis to 0.44 mg/kg/day at 3 months and 0.16 mg/kg/day at 6 months after diagnosis. Use of mycophenolate mofetil increased from 25.5% to 56.9% within 6 months after diagnosis. All children achieved LLDAS (median 186 days) and 72.5% remained in LLDAS >50% of time. 52.9% children achieved CR on Tx, and only 21.6% children achieved CR off Tx.ConclusionsLLDAS is an attainable treat-to-target goal in contrast to CR on and off Tx. Even more, LLDAS can be reached with limited use of corticosteroids with early introduction of immunosuppressives.

Update of Multicenter, Retrospective Evaluation of Overall Response and Failure Free Survival Following Ruxolitinib Therapy for Heavily Pre-Treated Chronic Gvhd Patients with Steroid-Failure: A Proposal of Risk Score Model for Failure-Free Survival

Background The REACH3 trial evaluating Ruxolitinib (RUX) treatment for steroid-refractory chronic GVHD concluded that RUX leads to significantly greater overall response and failure-free survival (FFS) than best available therapies (NEJM 2021). We reported a real-world experience of RUX in 47 chronic GVHD (cGVHD) patients, with 36% overall response rate (ORR) at 6 months (ASH 2020). The present study expanded this to 115 pts, evaluating ORR, FFS and overall survival (OS), and explored prognostic factors associated with clinical outcomes. Patients and methods A total of 115 patients treated with RUX for cGVHD from 2016 to 2021 at 5 sites were evaluated retrospectively. Patients and disease characteristics are as follows: median age 57.5 years; males 67 (60%); organ involvement at the time of RUX: skin 75.7%, mouth 51.3%, eye 42.6%, gastrointestinal 19.1%, liver 39.1%, lung 31.3%, and musculoskeletal 38.3%. Out of 108 pts with available HCT-CI prior to HCT, 29 pts (26.9%) had HCT-CI score 3 or higher, while 79 (73.1%) had HCT-CI score 0-2. The ORR were assessed at months 3, 6 and 12, retrospectively. Treatment failure was defined as 1) resistance requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance to treatment. FFS and OS were calculated from the day of starting RUX therapy for cGVHD treatment. For risk factor analysis, logistic regression was adopted for ORR at 6 months, while Cox's proportional hazard model was implemented for FFS and OS at 12 months. The following variables were evaluated for risk factor analysis: GVHD-related factors (cGVHD severity, no. of organ involvement, prednisone dose or RUX dose at start, previous history of acute GVHD); host factors (age or performance status at RUX starts, sex, HCT-CI comorbidity score pre-HCT); transplant factors (conditioning intensity; donor type, HLA match, T-cell depletion). From those variables identified as significant in the multivariate analysis, a prognostic risk score was generated as the sum of adverse risk factor scores. Results A total of 115 pts had severe (n=69, 60%) or moderate grade (n=44, 38.3%) cGVHD except 2 (1.7%) who had mild grade cGVHD with high-risk features. The median number of organ involvement was 3 (range 1-7). 96 pts (84.2%) received RUX as 4 th line or beyond for cGVHD treatment. The previous treatments included mycophenolate mofetil (n=46, 40.0%), extracorporeal photopheres (n=45, 39.1%), Imatinib (n=13, 11.3%), and Ibrutinib (n=9, 7.8%). RUX was started at 10-20 mg daily as the initial dose, then maintained at 20mg daily in two divided doses on months 3, 6 and 12. With a median follow-up duration of 12 months, ORR was attained in 46.8%, 61.8% and 62.3% at 3, 6 and 12 months, similar to 49.7% ORR rate at 6 months in the REACH3 study. ORR in the range of 48.1-64.5% at 6 months was observed across all the organs involved. No difference in ORR was noted between steroid-resistant vs steroid-dependent cGVHD, or according to previous treatment with TKI drug for GVHD. For ORR, severe grade cGVHD showed a lower ORR rate at 46.8% at 6 months compared to those with moderate/mild grade cGVHD at 81.1% (p=0.001). In terms of prednisone dose reduction, by 12 months, more than half of pts (63.8%) could taper prednisone doses below 0.1mg/kg/day, while the proportion of pts on prednisone dose below 0.1mg/kg/day was 14.83%, 33.6%, 47.6%, and 63.8% at month 0, 3, 6 and 12, respectively. A total of 39 failures (33.4%) were noted, including resistance requiring switch to other therapy (n=17), NRM (n=14), relapse of primary disease (n=3) and intolerance (n=5). The FFS rate in the overall population was 64.6% (54.1-73.2), while the OS rate was 83.3% (74.4-89.4%) at 12 months. For FFS, two risk factors were identified for FFS (Figure): 1) Severe grade cGVHD at RUX start (p=0.008, HR 2.496 [1.229-5.072]); 2) HCT-CI comorbidity 3 or higher (p=0.001, HR 2.802 [1.493-5.259]). When a risk score model was generated, it stratified pts according to the FFS at 12 months (p=0.0001): 85.8% in score 0 (n=32); 58.7% in score 1 (n=57); and 36.8% in score 2 (n=19). Conclusion: Updated results confirm that RUX is an effective treatment option for cGVHD pts, even including heavily treated pts. Also, favorable response was observed across all organs involved with GVHD. Failure of RUX is associated with cGVHD severity and HCT-CI score. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Elemary: Jazz, BMS, Abbvie, Novartis, Pfiz: Membership on an entity's Board of Directors or advisory committees; Pfizer, Janssen: Membership on an entity's Board of Directors or advisory committees. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Kim: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Paladin: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding. OffLabel Disclosure: This presentation discusses the use of ruxolitinib for chronic GVHD. This indication is under FDA review.

Propensity Score Matching Analysis Comparing Extracorporeal Photopheresis (ECP) Vs Best Available Therapy in Third Line or Later Treatment of Chronic Graft-Versus-Host Disease (cGVHD)

*DB and DK contributed to the work equally Background Prospective randomized controlled data comparing extracorporeal photopheresis (ECP) to other treatments for chronic graft vs host disease (cGvHD) as third-line or later therapy are limited, despite its clinical benefit observed in patients (pts) who failed ≥ 2 lines of previous therapy. Our single-center experience has reported promising results, including 68.3% failure-free survival (FFS) and 85.9% overall survival (OS) at 12 months in 75 heavily pre-treated cGvHD pts treated with ECP (ASH 2021 Abstract ID 152640). The present study compared outcomes, using propensity-score matching (PSM), between ECP ("ECP group", n=74) and a historical cohort treated with best available therapy (BAT) as third-line or later treatment from 2007 to 2021 ("BAT group", n=132). Statistical endpoints such as FFS and OS, as well as steroid dose reduction were evaluated instead of overall response due to limited response assessment data available from retrospective chart review. Patients and methods The BAT group received MMF (n=71, 53.8%), prednisone (n=37, 28.0%), prednisone/cyclosporine (n=7, 5.3%), rituximab (n=7, 5.3%), and others (n=10, 7.6%). There was an imbalance in characteristics between the two groups, as expected; the ECP group had more pts with severe cGVHD (91.1% vs 20.5%; p&lt;0.001), fewer with a previous history of acute GVHD (aGvHD: 60.8% vs 78.0%; p=0.008), and fewer on a prednisone dose ≥0.5mg/kg/day (37.8% vs. 90.5%; p&lt;0.001). PSM analysis was applied to adjust risk factors imbalanced between groups, including cGVHD grade (mild/moderate vs severe), aGVHD history, and baseline prednisone dose (&lt;0.5 vs. ≥ 0.5 mg/kg/day). A total of 54 pts (27 case-control pairs) were selected via PSM within 0.2 of a calliper difference, resulting in the balancing of risk factors between groups: cGVHD severity (p=0.941), aGVHD history (p=0.75) and prednisone dose ≥ 0.5 mg/kg/day (p=0.788). FFS and OS were calculated from the day of starting ECP or BAT, and were compared using Cox's hazard model. Daily prednisone dose at months 0, 3 and 6 were calculated divided by body weight (kg), and the proportions of pts on prednisone ≤ 0, 0.1, 0.2 and 0.5mg/kg/day were compared. Results In the overall cohort (n=206), with a median 29 months of follow-up, 114 treatment failures (55.3%) occurred. While the non-relapse mortality (NRM) was similar in both groups, the ECP group showed a lower rate of resistance requiring therapy switch. Failure was noted in 27 ECP pts (36.4%) due to causes including resistance/intolerance requiring a switch to other therapy (n=15; 20.3%), NRM (n=11, 14.8%), and relapse (n=1; 1.4%), while 87 failures (65.9%) were noted in BAT pts due to resistance requiring a switch to other therapy (n=63; 47.7%), NRM (n=7; 5.3%), and relapse (n=17; 12.9%). In the overall cohort, the 12-month FFS was 68.3% and 32.0% in ECP and BAT groups (p&lt;0.0001; Fig 1A), while OS was 86.2% and 82.2% in ECP and BAT groups, respectively (p=0.333; Fig 1B). In the PSM cohort (n=54), the ECP group showed a survival benefit at 12 months: FFS was 65.8% in the ECP group vs. 30.5% in the BAT group (p=0.00226; Fig 2A), and OS was 76.6% in the ECP group vs. 67.1% in the BAT group (p=0.0977; Fig 2B). Multivariate analysis in the PSM cohort confirmed that ECP was superior to BAT for FFS (p=0.024, HR 0.317 [0.117-0.859]) when adjusted for other risk factors including cGVHD severity, aGvHD history, age, HCT-CI score and prednisone dose ≤0.5mg/kg/day. Prednisone doses were gradually reduced over time; the median doses of prednisone at months 0, 3, and 6 were 0.35, 0.22 and 0.11 mg/kg/day, respectively, in the ECP group vs. 0.96, 0.24 and 0.19mg/kg/day in the BAT group. ECP also showed better kinetics of steroid dose reduction over time; the proportions of pts who discontinued prednisone at months 0, 3 and 6 were 16.2, 17.6% and 32.4% in ECP group vs. 0.8%, 0% and 2.5% in BAT group (Fig 3). The differences in the proportion of pts (delta) who discontinued prednisone in the ECP vs. BAT groups were 15.4%, 17.6% and 29.9% at 0, 3, and 6 months, respectively. Conclusion In the current study using PSM analysis, use of ECP was associated with a superior FFS to BAT when used as third-line or later therapy in cGVHD patients who failed at least 2 lines of previous therapy. Use of ECP also allowed for better steroid tapering in comparison to BAT. Figure 1 Figure 1. Disclosures Patriquin: Alexion: Consultancy, Honoraria, Speakers Bureau; BioCryst Pharmaceuticals: Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Kim: Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria.

95 Baseline body-mass-index and risk for obesity in children with rheumatic disease starting high-dose prednisone therapy

Primary Subject area Rheumatology Background Prednisone is a glucocorticoid (GC) medication commonly used in moderate (&gt;7.5 mg/day) to high doses (≥ 1 mg/kg/day to maximum 60 mg/day) for children with moderate to severe presentations of rheumatic disease, including systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), and juvenile dermatomyositis (JDM). Adverse effects (AE) to GCs impose a significant burden on health and quality of life including frequent development of weight gain, mood changes, sleep difficulties, osteoporosis, and Cushingoid features, amongst others. Objectives We sought to evaluate a possible relationship between baseline patient body-mass-index (BMI) measure and development of select GC-mediated toxicity within the first 12 months of starting moderate or high-dose prednisone therapy using conventional weight-based dosing of prednisone. Secondary outcomes were to examine rates of GC-mediated hypertension, osteopenia, and osteoporosis. Design/Methods We performed a retrospective chart review on children with rheumatic disease aged ≤ 17 years treated with moderate and high-dose prednisone therapy at a single Canadian academic hospital between January 1, 2010 and December 31, 2019. Demographic variables collected included diagnosis, age, sex, ethnicity. Clinical variables collected include weight, height, and body-mass-index (BMI), hepatitis (AST&gt;41 U/L, ALT&gt;40 U/L, or GGT&gt;60 U/L), proteinuria (&gt;0.1 g/L), and presence of hypoalbuminemia (&lt;38g/L) at baseline. We collected weight, height, and body-mass-index (BMI), at 6 and 12 months, the maximum BMI, and transformed them to z-scores according to the World Health Organization's Child Growth standards. Cumulative prednisone dose (mg/kg/12 months), total days on prednisone in the first 12 months of therapy were also obtained, in addition to bone-mineral-density cores after 12 months of prednisone therapy. Baseline characteristics, which were significant for the subsequent development of obesity during the first 12 months at the bivariate level (p &lt; 0 .05), were included as predictors of obesity in separate logistic regression analyses. In each regression analysis, we also adjusted for baseline BMI, and for confounding variables of hepatitis, hypoalbuminemia (albumin less than 38 grams per litre), proteinuria and prednisone dose. We conducted a complete case analysis, and all analyses were performed using SPSS v.26 (IBM Corp., Armonk, NY, USA), and p-values &lt; 0 .05 were considered statistically significant. Results Seventy-four charts were reviewed, and 72 patients met criteria for analysis. The median prednisone dose was 35 mg per day (IQR 20 to 60 mg), and median duration of therapy was 302 days (IQR 126.75 to 581.25). Thirty-five (48.6%) patients developed obesity, 33 (45.8%) hypertension, five (7.0%) osteopenia, and three (4.2%) osteoporosis. Greater BMI at baseline was associated with greater total weight gain (OR 4.04, 95% CI = [1.98-8.33], p &lt; 0 .001). Conclusion Greater baseline patient BMI may be a predictor of weight gain on high-dose prednisone therapy in children with rheumatic disease requiring high-dose therapy. Further work is required to determine methods for individualized prednisone dosing and counseling and behavioral interventions to mitigate risk for weight gain.

Initial therapy of chronic graft vs. host disease: Analysis of practice variation and failure-free survival

Prior clinical trials largely considered prednisone 1mg/kg/day with or without calcineurin inhibitor as standard initial therapy for chronic graft vs. host disease (cGVHD) but uncertainty remains regarding the extent of practice variation and whether this affects subsequent outcomes. We assembled a cohort of 745 cGVHD patients treated with initial systemic immune suppressive (IS) therapy from three prior Chronic GVHD Consortium observational studies. Initial therapy was defined as first IS therapy started for cGVHD or prednisone increased to ≥ 0.4mg/kg/day from lower doses within 30 days before cGVHD diagnosis to any time afterward. Initial therapies were non-prednisone IS therapies (n=137, 18%), prednisone alone (n=411, 55%), or prednisone plus other IS therapy (n=197, 26%). In multivariate analysis, initial therapy group was not associated with FFS (failure-free survival, a composite of death, relapse, new IS therapy), overall survival (OS) or non-relapse mortality (NRM). Among the prednisone-based approaches, steroid dose (mg/kg/day) was &lt;0.25 (9%), 0.25-0.74 (36%), 0.75-1.25 (42%), or &gt;1.25 (13%). Prednisone dose within the steroid-treated patients was not significantly associated with FFS, OS, or NRM. No significant interactions were detected between overall cGVHD severity and either initial therapy group or prednisone dose for the outcomes of FFS, OS, or NRM. These observational data document heterogeneity in more contemporary cGVHD initial treatment practices, including prednisone dose and use of non-steroid approaches. This variation was not associated with FFS, OS, or NRM. Prospective trials are needed to verify efficacy of reduced-dose prednisone or prednisone-free initial therapy approaches.

Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR &gt;10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

POS0216 GREATER HIGH-DENSITY LIPOPROTEIN LEVELS OVER TIME ARE LINKED TO DECREASED CORONARY PLAQUE FORMATION AND REGRESSION AND STABILIZATION OF HIGH-RISK LESIONS IN RHEUMATOID ARTHRITIS

Background:The relationship between serum lipoproteins and cardiovascular disease risk in rheumatoid arthritis (RA) is complex1. Their levels and function may vary based on disease activity and medication use. Beneficial effects on high-density lipoprotein (HDL-C) levels, structure and behavior, in response to treatment have been described. However, the impact of HDL-C levels over time on coronary atherosclerosis progression in RA is unknown.Objectives:We here evaluated the influence of HDL-C levels over time on long-term coronary plaque formation and progression in patients with RA.Methods:One hundred one RA patients without symptoms or history of cardiovascular disease who participated in a computed tomography angiography study of coronary atherosclerosis had repeat assessments after 6.9±0.3 years to evaluate plaque progression. Clinical, laboratory and medication data were recorded at baseline and regular outpatient follow-up visits thereafter. Time-averaged HDL-C was calculated for each patient using available consecutive HDL measurements between baseline and follow-up. Robust logistic regression assessed the association between time-averaged HDL-C and likelihood of new plaque formation in segments without plaque at baseline, and transition of prevalent mixed plaque to calcified plaque. Robust multinomial logistic regression evaluated the effect of time-averaged HDL-C on likelihood of new non-calcified, mixed or calcified plaque formation in segments without plaque (compared to remaining without plaque), and non-calcified plaque regression or transition to mixed or calcified plaque at follow-up (compared to remaining non-calcified). All models accounted for clustering of coronary segments within patients and adjusted for Framingham D’Agostino risk score, proximal segment location, time-averaged CRP, cumulative prednisone dose, bDMARD duration, statin duration, waist-to-height ratio, and time-averaged triglycerides.Results:Participants were mostly female (n=87, 86.1%), with a mean ± standard deviation (SD) age of 51.5±10.3 years and time-averaged HDL-C of 51.7±13.9. Ninety-seven new plaques formed in segments without plaque at baseline; 20 were noncalcified, 21 were mixed, and 56 were calcified. Time-averaged HDL-C had no effect on new total plaque formation (adjusted odds ratio-OR 0.88 [95% CI 0.64-1.21]). However, each 1-SD increase in time-averaged HDL-C associated with a 44% reduced likelihood of new non-calcified plaque formation at follow-up (adjusted OR 0.56 [95% CI 0.35-0.92], Figure 1). In contrast, there was no effect of time-averaged HDL-C on new mixed or calcified plaque formation. Of 98 non-calcified plaques at baseline, 42 did not change at follow-up, 32 regressed (disappeared), 16 transitioned to mixed and 8 to calcified plaques. Each SD increase in time-averaged HDL-C yielded a 2.2-fold greater likelihood of non-calcified plaque regression (adjusted OR 2.21 [95% CI 1.02-4.83]). Sixteen of 52 mixed plaques present at baseline transitioned to more stable calcified lesions, and time-averaged HDL-C (per 1-SD increment) predicted a 3.5-fold increased likelihood of transition of mixed to fully calcified plaque (adjusted OR 3.56 [95% CI 1.25-10.17]).Conclusion:Higher HDL-C over time predicted regression of existing and decreased formation of new higher-risk non-calcified plaque. It also associated with transition of vulnerable mixed plaque to more stable fully calcified plaque. These effects were independent of RA treatment duration, prednisone dose and statin exposure.References:[1]Toms TE et al. Curr Vasc Pharmacol. 2010;8:301–326.Figure 1.Impact of HDL-C over time on coronary plaque progression in RADisclosure of Interests:George Karpouzas Speakers bureau: Sanofi/Genzyme/Regeneron, Consultant of: Sanofi/Genzyme/Regeneron, Grant/research support from: Pfizer, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared