Citations

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

Abstract Objective COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys. Methods The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups. Results We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)]. Conclusion Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.

Abstract Rationale Candida albicans (CA) is ubiquitous and individuals are often immunized against it. However, skin testing reactivity with CA-antigens (CAAg) have been variable during latent tuberculosis infection (LTBI) screening. We hypothesized that the use of a CAAg in an ELISPOT assay would provide a positive control to study tuberculosis (TB)-antigen specific immune responses. Objective To test an ELISPOT with TB-antigens and control conditions, including a purified protein derivative of CA, CAAg, that differentiates subjects with LTBI from unexposed subjects. Methods An ELISPOT that detects interferon-γ from PBMCs (2×105 cells) after 2-day incubation with TB antigens, controls, including CAAg, and co-stimulatory antibodies. We studied two independent cohorts of subjects with LTBI diagnosis based on TST and IGRA results per clinical guidelines. Results One-hundred thirty-nine subjects were studied in 2010–12, including 27 patients with LTBI and 21 IGRA(−) unexposed subjects. ELISPOT with TB-antigens but also CAAg - nil (78 [21 – 182] vs. 9 [1 – 50] cfu) differentiated LTBI subjects from unexposed ones (P<0.005). A second cohort of 76 subjects were studied in 2015–17, including 14 patients with LTBI and 24 unexposed controls, which showed similar statistical results. Positive control (SEAB/antiCD3) did not differentiate these study groups. ELISPOT results with CAAg correlated with results of ELISPOT with TB antigens in all subjects (P<0.001), and in the LTBI and unexposed groups independently. Conclusion An ELISPOT assay that includes CAAg revealed immune reactivity that is prevalent in LTBI. The immune subsets that react to both CA and mycobacterial antigens are unclear, but may be relevant for both TB and candida immunity.

Abstract Introduction Previous studies have shown that sleep disordered breathing (SDB) is common in patients with Interstitial Lung Disease (ILD), and oximetry is often used for screening prior to further diagnostic testing. Current guidelines recommend polysomnography (PSG) for diagnosis of SDB in patients with significant pulmonary disease, however, home sleep apnea tests (HSAT) are increasingly used in clinical practice for a variety of reasons despite lack of evidence regarding accuracy in this population. In this study, we evaluate the correlation between screening oximetry, a commercial brand HSAT (WatchPAT®) and PSG to examine the diagnostic accuracy of this HSAT technology in patients with ILD. Methods The institution electronic medical record was screened for patients with a diagnosis code for ILD who underwent screening oximetry followed by PSG or HSAT using peripheral arterial tonometry from July 1, 2012 to present. Clinical review confirmed presence of ILD according to American Thoracic Society guidelines. Among the respective cohorts, Paired Wilcoxon Test was used to compare the oximetry 4% oxygen desaturation index (ODI) to the HSAT ODI and PSG apnea-hypopnea index (AHI) as well as percent time spent below oxyhemoglobin saturation of 89%. Spearman correlation was used to correlate the oximetry ODI and parameters of SDB on HSAT and PSG. Results Data was analyzed for 25 patients who had undergone oximetry/HSAT and for 25 patients who had undergone oximetry/PSG. Oximetry ODI showed no significant difference from PSG AHI (p = 0.2635) or between HSAT ODI (p = 0.0755), and no difference was seen in hypoxic time between oximetry and PSG (p = 0.9789). Hypoxic time on HSAT was significantly longer than that on oximetry (p < 0.001). Using HSAT ODI as the standard, HSAT AHI and respiratory disturbance index (RDI) showed rs of 0.9638 and 0.8913 respectively, while oximetry ODI was 0.3893. Compared to PSG AHI, the PSG RDI and oximetry ODI rs were 0.9759 and 0.7407 respectively. Conclusion Among patients with ILD, screening oximetry appears to correlate more strongly with indices of SDB and hypoxic time on PSG rather than HSAT. Further studies are warranted to evaluate efficacy of additional HSAT testing modalities in this patient population. Support (If Any)

Abstract Miliary tuberculosis (TB) is a rare and potentially fatal form of disseminated TB. Disseminated TB involving the central nervous system (CNS) may be seen in up to nearly a third of miliary TB cases. We describe a case of miliary TB with CNS involvement and suspected hepatobiliary involvement in an immunocompetent patient after an elective spine surgery. Given the patient's unusual presentation in the absence of risk factors for TB, diagnosis was delayed. We were later informed that the bone graft he received during spine surgery, FiberCel (“FiberCel”) Fiber Viable Bone Matrix (Aziyo Biologics, Inc, Richmond, Calif), was contaminated with TB. This patient is 1 of almost 2 dozens reported to be affected. This case represents a novel presentation of TB due to contaminated cadaveric bone allograft matrix implantation, with notable rapid dissemination and CNS involvement.

Abstract Background: Treatment of multiple myeloma (MM) commonly encompasses combination of drugs within the three drug classes including proteasome inhibitors (PIs), immunomodulators and (IMiDs), and monoclonal antibodies, both for newly diagnosed and relapsed disease. With increasing appreciation of disease heterogeneity based on underlying genetic abnormality, and demonstration of efficacy of venetoclax in patients with t(11;14) MM, the outcomes with commonly used MM regimens among the different cytogenetic subgroups are of great interest. Venetoclax, a BCL-2 inhibitor, is being studied in t(11;14) positive MM patients who have received at least two prior lines of treatment (NCT03539744; CANOVA). However, outcomes in previously treated t(11;14) MM patients using standard of care approaches in the real-world setting is limited. Patients and methods: This non-interventional, retrospective observational cohort study included patients with t(11;14) MM from the International Myeloma Working Group (IMWG) retrospective study of t(11;14) MM. From the overall cohort, patients with t(11;14) MM receiving pomalidomide + dexamethasone (PomDex) in ≥3 rd line were selected, similar to those being enrolled in the ongoing CANOVA trial. Patients were also required to have prior exposure to lenalidomide and a PI without a history of transplant within 16 weeks prior to PomDex initiation. Patients enrolled in a clinical trial were excluded. Overall best response, time to next therapy (TTNT) as a surrogate measure for progression-free survival (PFS) and overall survival (OS) were assessed after initiation of PomDex. All analyses were descriptive in nature and were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Results: Fifty-two patients who met the inclusion criteria were analyzed. Median age was 63 years, 60% were male. Patients had a median of 3 prior lines at start of PomDex, at a median of 4.3 years from diagnosis; 52% had a prior transplant. A PR or better was observed in 34% of patients with PomDex. The median TTNT for this cohort was 6.1 months and median OS was 19.2 months. Conclusion: This retrospective study of non-trial patients with t(11;14) MM provides a benchmark for newer therapies in this patient population for comparison with both venetoclax dexamethasone in the ongoing CANOVA study as well as combinations using the pomalidomide backbone. Disclosures Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company. Kumar: Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Gonzalez De La Calle: Celgene-BMS, Janssen, Amgen: Honoraria. Mangiacavalli: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria. Kastritis: Janssen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Esteves: AbbVie: Consultancy; BMS: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Delforge: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee: Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Oncopeptides: Consultancy; Adaptive: Consultancy; GSK: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Sanofi: Consultancy. Arriola: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Ross: AbbVie: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Manthena: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Durie: Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy; Amgen: Other: fees from non-CME/CE services .