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BackgroundFlare of Rheumatoid Arthritis (RA) following COVID-19 vaccination has been reported with a low occurrence observed in those patients with disease remission. However, no local data is available in our multi-ethnic Malaysian population.ObjectivesTo evaluate the prevalence of RA flare in Malaysian patients following COVID-19 vaccination and its associated risk factors.MethodsThis was a cross-sectional study assessing RA flare based on patient-reported disease flare through self-administered questionnaires and physician-reported flare. Patient self-reported disease flare was defined as ‘a sudden worsening of rheumatology condition or arthritis within 1 month post-vaccination' while physician-reported flare was defined as ‘an increment of disease activity score 28-joint documented within 3 months post-vaccination‘ from either a scheduled or unscheduled clinic visit. A total of 186 RA patients attended the rheumatology clinic in Hospital Putrajaya from May to July 2022 who completed the primary COVID-19 vaccination under the Malaysian National Vaccination Programme were recruited. Demographic data, disease parameters including serology for rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), cessation of disease modifying anti-rheumatic drugs (DMARDs) around vaccination, type of vaccines and adverse events were examined using descriptive and univariate analyses.ResultsMajority (93%) of RA patients enrolled were female with a mean age of 58 years old (standard deviation, SD 12.2) and mean disease duration was 12 years (SD 7.7). More than half were seropositive (66% RF, 63% ACPA) with 47.4% had double seropositivity (RF and ACPA positive). All patients received DMARDs with the majority (71%) were on methotrexate (MTX), 21.5% were on leflunomide, 17.7% on other DMARDs, with a small proportion (14%) of patients were receiving prednisolone. Only 4.8% of patients were on biologics or targeted synthetic disease modifying anti-rheumatic drugs. Half of the patients were in remission prior to vaccination. 62% of patients received Pfizer-BioNTech vaccine as the primary vaccine, followed by Sinovac-CoronaVac (24.6%) and Oxford-AstraZeneca (13.4%) vaccines. A booster dose had been administered to 80% of patients, of which 88.7% was Pfizer-BioNTech vaccine. MTX therapy were discontinued in 39.4% of patients (n=52) post-vaccination for a week duration. The prevalence of RA flare was only 12.9% (n=24) in which 14 were self-reported and 10 were physician-reported flares (4 severe flare, 6 mild-moderate flare). Flare rates were higher during the first and second dose of vaccination with 29.2% respectively, and only 12.5% were reported after booster vaccination. Common vaccine adverse effects were fever (16.8%), myalgia (8.6%) and arthralgia (6.4%). There were no significant differences in the occurrence of flare post-vaccination between age, gender, disease activity prior to vaccination, types of vaccine, usage of MTX and prednisolone, and discontinuation of MTX post-vaccination. Although seropositivity did not exhibit statistically significant flare rate post vaccination, sub-analysis revealed four times higher rate of flare in those who has double positivity compared to seronegative RA patients (12% vs 4%).ConclusionPrevelance of RA flare post-COVID-19 vaccination in Malaysian RA population is low. No significant associated risk factors were identified although double seropositivity appeared to have higher number of flares.References[1]Bixio, R., Bertelle, D., Masia, M., Pistillo, F., Carletto, A. and Rossini, M. (2021), Incidence of Disease Flare After BNT162b2 Coronavirus Disease 2019 Vaccination in Patients With Rheumatoid Arthritis in Remission. ACR Open Rheumatology, 3: 832-833.[2]Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, Lai FTT, Wan EYF, Wong CKH, Chan EWY, Lau CS, Wong ICK. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022 Apr;81(4):564-568.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Objectives: Acne is a leading skin problem in adolescents. After the end of COVID-19 pandemic, with the gradual transition to the routine life, we started to encounter more severe forms of acne in the last 6-month than we had seen before in the 10 year period of our Paediatric Dermatology outpatient clinic. Method(s): We evaluated the demographic and clinical characteristics, COVID infection and vaccination status, and treatment of patients who were treated at our Paediatric Dermatology outpatient clinic in the last 6 months due to severe acne. Result(s): One of our patients had acne fulminans, and four patients had acne conglobata. The common features of these patients presenting with severe acne were that they were young boys aged 15- 16 years, medium height, normal weight, and skin type 3-4. All patients had a family history of acne in their parents. They had no known comorbidities, additional treatment, history of nutritional supplement use, or accompanying arthralgia or arthritis. Four patients were initially treated with isotretinoin for severe acne, developed acne conglobata, and one developed acne fulminans during the follow-up period. Dapsone therapy was initiated in all patients according to the severity of the lesions, and adalimumab was administered to acne fulminans. Discussion(s): The frequent occurrence of severe forms of acne after the pandemic raises the question of whether COVID-19 infection or vaccination may play a role in its aetiology. Cases of mask-related acne exacerbation during COVID-19 have been well-described in the literature. However, there are no data on the effects of COVID-19 vaccination or infection on the development of severe acne. In this report, we present cases of adolescent patients with severe acne to investigate the possible reasons for the increasing number of severe acne cases presenting to our outpatient clinic during the postpandemic period.
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BackgroundAnti-synthetase syndrome (ASS) is a rare auto-immune condition that combines autoantibodies and specifics clinical manifestations, including myositis, interstitial lung disease (ILD), polyarthritis, mechanic's hands, Raynaud's phenomenon, and unexplained fever. The hallmark of this syndrome is the presence of anti-aminoacyl-tRNA-synthetase (ARS) antibodies. Several anti-ARS antibodies have been described, anti-Jo1 being the most common, followed by anti-PL7, anti-PL12, anti-OJ, anti-EJ, anti-KS, anti-YRS, and anti-Zo. According to a recent epidemiological survey, the rising number of patients with autoimmune diseases, including idiopathic inflammatory myopathies (IIM) coincides with the COVID-19 pandemic.ObjectivesTo evaluate the clinical characteristics of ASS patients with different anti-ARS antibodies from a tertiary rheumatology center.MethodsWe conducted a retrospective, single-centered study on consecutive patients diagnosed with ASS from 1 January 2015 to 31 December 2022. Clinical and serologic data were obtained by medical records review from hospital database. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were tested using commercial ELISA kits. We included all patients fulfilling Connor's criteria for ASS.ResultsSixty-one patients (44 females) with mean age 54.4 (13.8) years were included. The most frequently reported clinical manifestation was arthralgia (68.8%), followed by Raynaud's phenomenon (67.2%), ILD (65.6%), myositis (46%), mechanic's hands (44.3%), arthritis (39.3%), and fever (18.0%). The typical triad for ASS, including myositis, arthritis and ILD was present in 17 patients. Twenty-eight (45.9%) patients were PL7+, 21 (34.4%) were Jo1+, 3 (4.9%) were PL12+, and 2 (3.2%) were OJ+. Seven patients were positive for more than two anti-ARS antibodies. The most frequently found MAA was anti-Ro52 (n=23, 37.7%). Of the 61 patients included, 41 (67.2%) patients were diagnosed in the last 3 years (COVID-19 pandemic). The most frequently detected MSA in ASS patients diagnosed during COVID-19 pandemic was anti-PL7 (25/28), while anti-Jo1 was the most common MSA in ASS patients diagnosed before 2020 (p<0.05) (Fig 1).The anti-Jo1+ patients were younger, have significantly more frequent muscle involvement and significantly higher levels of CK than anti-PL7+ patients (p<0.05). The co-occurance of anti-Ro52 antibodies was more frequently observed in anti-Jo1+ patients (n=11, 52.4%) than in anti-PL7+ patients (n=6, 21.4%) (p<0.05). We did not find statistically significant differences between ASS groups regarding sex, disease duration, clinical manifestations including dermatologic lesions, Raynaud's phenomenon, arthralgia/arthritis, ILD, fever, and cancers (all p>0.05).ConclusionASS patients have heterogenous manifestations, and different types of anti-ARS antibodies are associated to distinct clinical and immunological features. The COVID-19 pandemic led to increase prevalence of ASS cases and to a remarkable shift in the anti-ARS antibodies profile, with increased frequency of anti-PL7 antibodies. Further studies are needed to investigate the link between SARS-CoV-2 infections and myositis.References[1]Witt LJ, et al. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016 Sep;23(5):218-226.[2]Gracia-Ramos AE, et al. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells. 2021 Dec 20;10(12):3592.[3]Connors GR, et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010 Dec;138(6):1464-74.[4]García-Bravo Let al. Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies. J Transl Autoimmun. 2022 Jun 30;5:100160.Figure 1.ASS patients with positive anti-ARS antibodies per year (from 2015 to 2022). The green line shows the PL7+ patients;and the orange line shows the Jo1+ cases.[Figure omitted. See PDF]AcknowledgementsI have no acknowledgements to declare.Disclosure of Inter stsNone Declared.
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The pandemic caused by COVID-19 has led to radical lifestyle changes worldwide, particularly in the Republic of Bulgaria, and was a factor for global changes in economics, politics, healthcare and daily life. Aim(s): The aim of the study was to analyze the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria. Material(s) and Method(s): The survey was conducted between August 1st, 2022 and September 1st, 2022 via an anonymous questionnaire consisting of 24 closed questions. A total of 1861 people, aged 18-69 years and older, took part in the survey after being selected randomly. The data were statistically processed via MS Excel. Result(s): The main source of information to the respondents on issues related to COVID-19 was the Internet (29,8%), followed by TV (26%) and the specialized website (Single information portal) - 15,9%. More than one-third (35,1%) of the respondents was afraid of getting infected and an equal share of participants reported that they have been infected with COVID-19. More than half of the respondents (52,5%) adhered to all the provisions of the governmental bodies related to limiting the COVID-19 pandemic. The most frequent symptom of post- COVID-19 syndrome was being easily fatigued (26,7%), followed by shortness of breath (13,4%) and persistent cough (11,6%). Conclusion(s): The survey could be useful in understanding what were the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria during the pandemic.Copyright © 2023 D. Penchev et al., published by Sciendo.
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Whipple disease is a rare multisystem inflammatory disease. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. We are reporting a case of a 46-year-old man who presented with fever, weight loss, and polyarthralgia for 2 months, and 1 month of diarrhea. The patient was thoroughly investigated for collagen diseases and COVID-19, with no definite diagnosis. A therapeutic trial by immunosuppressive drugs provided partial remission followed by a marked rebound of the symptoms. His occult blood in stool was positive and subsequent upper endoscopy with proximal small intestinal biopsies showed the pathological features of Whipple's disease. The patient showed a dramatic improvement following treatment with ceftriaxone and trimethoprim-sulfamethoxazole. Despite the rarity of Whipple's disease, its course mimics many rheumatological diseases, inflammatory bowel disease, and COVID-19 disease. It should always be a part of the differential diagnosis of obscure polyarthralgia and chronic diarrhea.Copyright © 2023 The Author(s).
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The clinical evaluation of the patient with COVID-19 allows better care, application of safety criteria and preventive measures. The disease progresses from mild to severe and critical. In this work, is evaluated in patients with COVID-19 clinical format to identify moderate to severe stages of the disease. Following a cohort of male and female patients over 18 years of age admitted to the Infectology Service of the General Hospital of Mexico. Each patient is studied using the"COVID-19 Infectology"clinical format and in the first 24 hours of admission, a real-time RT-PCR molecular test is performed for SARS-CoV-2 infection. 65 patients classified as severe COVID-19 were studied, the RT-PCR was positive in 60 patients and negative in 5, clinical data did not differ from the positive ones and the 5 negative were considered false negative cases of the molecular test. There were no differences between positives and negatives with Fisher's test, and no difference in age, comorbidities, or prognostic evaluation with Student's t test. The conclusion is that the clinical format"COVID-19 Infectology"allows to recognize the cases and identify those that are in a severe evolution.Copyright /© 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.
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BackgroundOlokizumab (OKZ), an IL-6 ligand inhibitor in doses of 64 mg every two weeks (q2w) or every 4 weeks (q4w) demonstrated significant improvements in signs and symptoms of RA. Due to lack of availability of the IL-6 receptor antagonists tocilizumab and sarilumab in the pandemic COVID-19 situation, RA patients (pts) were switched to OKZ as a registered drug in Russia in 2022.ObjectivesTo investigate safety and efficacy of OKZ after switching from an IL-6 receptor inhibitor in clinical practice.MethodsThis retrospective cohort study included available efficacy and safety data of OKZ in pts with RA after switching from tocilizumab (IV or SC) or sarilumab (SC) from 11 of participating centers.Efficacy assessments and routine biochemical data were analyzed using descriptive statistics – mean with standard deviation for continuous parameters and absolute and relative frequency for binary variables. AE were reported by participating centers according to pt's files. The statistical significance of data of the analyzed variable at a particular visit compared with previous visits or with the Switch visit was determined using paired t-test. Fisher's exact test or chi-square test was used to compare the proportion of pts with improvement/no change and worsening. All tests were 2-tailed, and a p-value <0.050 was considered statistically significant. As this is an observational study, the statistical criteria have not been pre-specified and therefore the data presented cannot be considered definitive but should be confirmed in future analyses.ResultsEfficacy and safety results were collected for 110 RA pts with a mean age of 47.8 (15.7) years, including 87 (79.1%) women. 77 (70.0%) pts were RF/ACPA positive. Mean RA duration was 13.1 (8.9) years and mean duration of treatment with an IL-6 receptor antagonist was 47.8 (30.0) months. Mean interval before switching was 54.7 (35.4) days with the main reason of unavailable IL6-R antagonist. Pts were treated with OKZ 64 mg q4w SC.Before initiation of OKZ, an increase of DAS28-CRP was observed due to a prolonged period after the last injection of the IL-6R inhibitor from 2.8 to 3.1 weeks in 32 pts on monotherapy who were transferred to OKZ faster (on average after 41.6 (23.8) days), and from 2.7 to 3.3 weeks in 73 pts on concomitant sDMARDs (60.0 (38.0) days). DAS28-CRP was improved to 2.8 on the second OKZ visit (S+1) in both groups. Response to OKZ was maintained over a period of 2 months with no difference between pts previously receiving an IL-6 R antagonist. Of note, lower disease activity based on DAS28-CRP of 2.5 and 2.6 was achieved after 8 weeks (S+2) of OKZ therapy compared to the previous IL-6R inhibitors treatment S-1 visit (P less 0.05) (Figure 1).Figure 1.Mean DAS28CRP over time, M(SD)[Figure omitted. See PDF]Abbreviation: S-2 and S-1 last visits before switching– S+1 and S+2 visits after switching,Treatment emergent AE occurred in 7 (6.4%) pts, the most common AE in 3 pts (2.7%) included arthralgia of hands and feet and transient leukopenia in 2 (1.8%) pts.Serious AE were reported by 1 (0.9%) pt (exacerbation of herpes infection that led to treatment discontinuation). No deaths were reported. There were no apparent differences in safety and efficacy outcomes between pts on OKZ monotherapy compared to combined treatment with csDMARDs. Only one pt was switched back to tocilizumab when it became available.Table 1.Summary of treatment emergent adverse events (safety population)NOKZ 64 mg q4w with MTX N=78OKZ 64 mg q4w monotherapy N=32Any AE51 carpal canal syndromeAny serious AE10Any AE leading to discontinuation of study drug10Any death00Any AE of special interest10Infections10Laboratory abnormalitiesHyperbilirubin-emiaALT, AST elevation less than 3 ULNALT, alanine transaminase;AST, aspartate transaminase;ULN, upper limit of normalConclusionIn pts with RA responding to an IL-6R antagonist, switching to OKZ was safe and well tolerated in clinical practice. The treatment response was maintained and in some pts disease activity moderately decreased in compariso to baseline level both in OKZ mono and combination therapy.Reference[1]J.Smolen, N Engl J Med 2022;387:715-726AcknowledgementsI have acknowledgements to Vinogradova I.B., Anoshenkova O.N., Antipova O.V., Baranov A.A., Bogdanova E.A., Grabovetskaya Y.Y., Ilivanova E.P.,Kalyagin A.N., Kushnir I.N., Lapkina N.A. Mokrousova M.V., Nesmeyanova O.B., Nikitina N.V., Shesternya P.A. and Yudina N.V.Disclosure of InterestsEugen Feist Consultant of: Abbvie, Eli Lilly, Galapagos, Medac, Novartis, Sanofi, Sobi, R-Pharm, Grant/research support from: Eli Lilly, Novartis, Pfizer, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer.
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Introduction In this study, we aimed to monitor anti-spike and anti-nucleocapsid antibodies positivity in healthcare workers (HCWs) vaccinated with two doses of inactivated CoronaVac (Sinovac, China) vaccine. Methods Overall, 242 volunteer HCWs were included. Of the participants, 193 were HCWs without history of prior documented COVID-19 (Group 1), while 49 had history of prior documented COVID-19 before vaccination (Group 2). The participants were followed up for SARS-CoV-2 antibodies positivity at four different blood sampling time points (immediately before the second vaccine dose and at the 1st, 3rd months and 141-150 days after the second dose). We investigated the serum IgG class antibodies against SARS-CoV-2 RBD region and IgG class antibodies against SARS-CoV-2 nucleocapsid antigen by chemiluminescent microparticle immunoassay (CMIA) method using commercial kits. Results We found positive serum anti-RBD IgG antibody in 76.4% of the participants (71% in Group 1;98% in Group 2) 28 days after the first dose. When the antibody levels of the groups were compared at the four blood sampling time points, Group 2 anti-RBD IgG levels were found to be significantly higher than those in Group 1 at all follow-up time points. Although anti-RBD IgG positivity persisted in 95.6% of all participants in the last blood sampling time point, a significant decrease was observed in antibody levels compared to the previous blood sampling time point. Anti-nucleocapsid IgG antibody was positive in 12 (6.2%) of participants in Group 1 and 32 (65.3%) in Group 2 at day 28 after the first dose. At the fourth blood sampling time point, anti-nucleocapsid antibodies were found to be positive in a total of 20 (9.7%) subjects, 10 (6.1%) in Group 1 and 10 (23.8%) in Group 2. Conclusions In this study, it was determined that serum antibody levels decreased in both groups after the third month after the second dose in HCWs vaccinated with CoronaVac vaccine.Copyright © GERMS 2022.
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BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities associated. However, few studies in the literature assessed the safety and immunogenicity of the COVID-19 heterologous vaccine schedules in patients with RA.ObjectivesEvaluate the safety and immunogenicity of two heterologous vaccine schedules against SARS-CoV-2 in patients with RA.MethodsThese data are from the study "SAFER - Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Immunogenicity and adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 plus additional dose of BNT162b2 or after two doses of inactivated SARS-CoV-2 vaccine CoronaVac plus additional dose of BNT162b2. The titers of neutralizing antibodies against the receptor-biding domain of protein spike (S) of SARS-CoV-2 (anti-RBD) were measured by chemiluminescence test after each dose of immunizers. Proportions between groups were compared using the chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test.ResultsA total of 107 patients with RA were include in the study, most of them female, with a mean age of 46 years. Biological disease modifying anti-rheumatic drugs (DMARDs) were used by 50 % of the patients and conventional synthetics DMARDs in 48 %. Two doses of CoronaVac plus additional dose of BNT162b2 was used in 66 patients and two doses of ChAdOx1 plus additional dose of BNT162b2 in 41. Only mild AEs were observed, mainly after the first dose. The most common AEs after all doses, regardless of the immunizer type, were pain at the injection, headache, arthralgia and myalgia. ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0,001) and arthralgia (68% vs 15%, p < 0,001) compared to CoronaVac. No patients had flare after the vaccination. The titers of anti-RBD after two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p < 0,001). However, after the additional dose of BNT162b2, the anti-RBD titers were similar in both groups (7.28 BAU/mL vs 7.06 BAU/mL, p = 0.56). Only two cases of COVID 19, with mild symptoms, were reported, one in each group.Figure 1.ConclusionChAdOx1, CoronaVac, and BNT162b2 vaccines are safe in RA patients. The frequency of local adverse effects, particularly pain at the injection site, is high. AEs are more frequent with ChAdOx1, especially after the first dose. The use of the immunizers does not change the degree of inflammatory activity of the disease. The immunogenicity of the two heterologous regimens analyzed was similar.References[1]Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study. JMIR Res Protoc.[2]Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.[3]Machado PM, Lawson-Tovey S, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis. 2022;81(5):695-709.[4]Tavares ACFMG, Melo AKG, Cruz VA, Souza VA, Carvalho JS, Machado KLLL, et al. Guidelines on COVID-19 vaccination in patients with immunemediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledg ments:NIL.Disclosure of InterestsNone Declared.
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Background: B-cell lymphoma-2 (Bcl-2) proteins play an important role in multiple myeloma (MM) cell survival and represent an attractive therapeutic target. In prior trials, a subgroup analysis of patients with t(11;14)-positive relapsed/refractory (R/R) MM showed the combination of a Bcl-2 inhibitor, a proteasome inhibitor, and dexamethasone improved progression-free survival with no increased mortality. BGB-11417, a Bcl-2 inhibitor, is more potent and selective than venetoclax. BGB-11417- 105 (NCT04973605) is a phase 1b/2 study assessing the safety and efficacy of BGB-11417 monotherapy, in combination with dexamethasone, or with dexamethasone+carfilzomib in patients with t(11;14)-positive R/R MM. Preliminary safety results for the combination of BGB-11417 + dexamethasone are presented. Method(s): Eligible patients had t(11;14)-positive R/R MM and had been exposed to a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy. Patients received 80-, 160-, 320-, or 640-mg BGB-11417 daily with 40-mg dexamethasone weekly until death, intolerability, or disease progression. Dose escalation was guided by a mTPI-2 design and overall review by a safety monitoring committee. Pharmacokinetics (PK) were also assessed. Result(s): As of 1 July 2022, 10 patients were enrolled in the 80-, 160-, and 320-mg (3 patients each) and 640-mg (1 patient) dose-escalation cohorts of BGB-11417 + dexamethasone. The median age was 69 years (range, 52-81) and median prior lines of therapy was 3 (range, 1-5). The median treatment duration was 3.2 months (range, 0.5-6.5). No patients experienced dose-limiting toxicity at any dose level. Three patients died whilst on study: 1 due to COVID-19 complications 157 days after treatment discontinuation (day 208), 1 due to progressive disease 50 days after treatment discontinuation (day 89), and 1 due to COVID-19 whilst on study treatment (day 78). No deaths were associated with study treatment. Two patients experienced Grade >= 3 treatment-emergent adverse events (TEAEs). One patient in the 160-mg cohort experienced Grade 3 increase in liver enzymes and lymphopenia. One patient in the 320-mg cohort experienced Grade 3 lymphopenia. The most common TEAEs were insomnia (50%), fatigue (30%), arthralgia (20%), back pain (20%), lymphopenia (20%), and nausea (20%). BGB-11417 exposure increased dose-dependently from 80 mg to 320 mg with high interpatient PK variability. BGB-11417 exposures after single and multiple doses appeared similar, indicating limited accumulation. Conclusion(s): BGB-11417 plus dexamethasone was generally well-tolerated in patients with R/R MM harbouring t(11;14) at doses <=640 mg. Efficacy data are forthcoming. Recruitment is ongoing in the US, Australia, and New Zealand;the BGB-11417, dexamethasone, and carfilzomib combination arm will open in the future.
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Aim: Coronavirus disease 2019 (COVID-19) has become a public health threat to people all over the world in 2020 and 2021. The Centers for Disease Control and Prevention (CDC) and WHO (World Health Organization) have named a novel disease multisystem inflammatory syndrome in children (MIS-C). Herein we aimed to present a group of pediatric patients with MIS-C, who were followed up in our clinic. Material(s) and Method(s): We retrospectively reviewed the medical records of patients who were followed up at our University Hospital with the diagnosis of MIS-C between January 2021 and May 2021. Result(s): The mean age of 9 patients was 87.4 +/-17.8 years (range 6-161 months);six of the patients were male. All patients had fever at admission. The duration of the fever was between 3 and 7 days. Four patients (44.4%) had terminal ileitis on ultrasonic examination. The laboratory tests of the patients revealed leukocytosis in 4 (44.4%) patients, anemia in 5 (55.5%) patients, thrombocytopenia in 1 (11.1%) patient, and a high CRP level in 8 (88.8%) patients. All patients had high sedimentation rates and procalcitonin levels. One (11.1%) patient was operated on for terminal ileitis. All patients were treated with steroids (1-2 mg/kg prednisolone) and IVIG (2gr/kg). Patients who needed ICU admission were also treated with vasoactive drug infusion (intravenous dopamine). Discussion(s): There is a need for increased awareness among pediatricians that MIS-C should come to mind, especially in patients with long-lasting fever and signs and symptoms that resemble Kawasaki disease.Copyright © 2022, Derman Medical Publishing. All rights reserved.
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BackgroundViral infections are known triggers of disease flares in idiopathic inflammatory myopathies (IIMs). Reports of post-COVID-19 flares of IIMs have raised suspicion of a possible role of SARS-COV-2 in their onset [1,2]. However, despite rising flare rates in this vulnerable patient group during the pandemic, the risk factors for post-COVID-19 IIMs flares remain unknown [3,4].ObjectivesDisease flares among patients with idiopathic inflammatory myopathies (IIMs) can lead to significant disability, though are poorly explored in the post-COVID-19 period. We analysed risk factors for post-COVID-19 flares in a global sample of IIM patients in a subset analysis as part of the ongoing COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsA cross-sectional patient self-reporting survey was circulated by the international COVAD study group (157 collaborators, 106 countries) to patients with autoimmune diseases and healthy controls from February-June 2022. Data was collected on demographics, autoimmune disease details, treatment history, comorbidities, COVID-19 history and course and COVID-19 vaccination details. Patients with IIMs who flared post COVID-19 were compared to those who did not using the χ2 test, factors found significant in univariate analysis and deemed clinically important, underwent multivariable analysis (binary logistic regression using the Enter method) with adjustment for age, gender, ethnicity, vaccine type, immunosuppression, autoimmune and non-autoimmune comorbidities, COVID-19 antibody status, and clinical symptoms of COVID-19. Statistical analyses were performed using IBM SPSS version 28.0, with statistical significance considered at p<0.05.Results15,165 respondents completed the survey of whom 1,169 contracted COVID-19. Of these, 207 had IIMs [median (IQR) age 57.0 (47.0-67.0), 71% female, 74.4% Caucasian]. We noted with concern that nearly a third of patients with IIMs (63/207, 30.4%) reported experiencing a flare. A past medical history significant for Asthma, (34.9% vs 6.9%, multivariable OR: 7.1;95%CI: 3.1-16.4, p<0.001) and specific clinical symptoms during COVID-19 including joint pains (multivariable OR: 6.05;95%CI: 1.60-22.9, p=0.008), and difficulty in breathing (multivariable OR: 3.43;95%CI: 1.09-10.8, p=0.036) were found to confer conferred a higher risk of flares (Table 1).Table 1Patient Reported Flares following COVID-19 infection among IIM patientsTotal IIMs (n=207)IIMs with flare after COVID-19 (n=63)IIMs without flare after COVID-19 (n=144)OR (95%CI)PAge (median, IQR) years57.0 (47.0-67.0)53.0 (47.0-62.0)59.0 (47.0-69.0)-0.024GenderMale Female60 (29.0) 147 (71.0)7 (11.1) 56 (88.9)53 (36.8) 91 (63.2)0.2 (0.09-0.5)< 0.001ComorbiditiesAsthma ILD32 (15.5) 31 (15.0)22 (34.9) 11 (17.5)10 (6.9) 20 (13.9)7.1 (3.1-16.4) 1.3 (0.5-2.9)<0.001 00.508Clinical features in previous COVID-19 infectionFatigue Myalgia Arthralgia Difficulty in breathing134 (64.7) 94 (45.4) 56 (27.1) 41 (19.8)52 (82.5) 44 (69.8) 36 (57.1) 27 (42.9)82 (56.9) 50 (34.7) 20 (13.9) 14 (9.7)3.5 (1.7-7.4) 4.3 (2.3-8.2) 8.2 (4.1-16.4) 6.9 (3.3-14.6)<0.001 <0.001 <0.001 <0.001ConclusionWe observed a high frequency of patients with IIM experiencing post-COVID-19 disease flares. A past history of Asthma and those with certain acute COVID-19 symptoms were at higher risk.References[1]Saud A, Naveen R, Aggarwal R, Gupta L. COVID-19 and Myositis: What We Know So Far. Curr Rheumatol Rep 2021;23:63.[2]Gokhale Y, Patankar A, Holla U, Shilke M, Kalekar L, Karnik ND, et al. Dermatomyositis during COVID-19 Pandemic (A Case Series): Is there a Cause Effect Relationship? J Assoc Physicians India 2020;68:20–4.[3]Gupta L, Lilleker JB, Agarwal V, Chinoy H, Aggarwal R. COVID-19 and myositis - unique challenges for patients. Rheumatology (Oxford) 2021;60:907–10.[4]Naveen R, Sundaram TG, Agarwal V, Gupta L. Teleconsultation experience with the idiopathic inflammatory myopathies: a prospective observational cohort study during the COVID-19 pandemic. Rheumatol Int 2021;41:67–76.Acknowledgements:NIL.Disclosure of InterestsSa dia Sasha Ali: None declared, Naveen Ravichandran: None declared, Parikshit Sen: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Mrudula Joshi: None declared, Sreoshy Saha: None declared, Rohit Aggarwal Consultant of: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Grant/research support from: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Vikas Agarwal: None declared, Hector Chinoy Speakers bureau: Speaker for UCB, and Biogen. HC was supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme., Grant/research support from: Has received grant support from Eli Lilly and UCB, consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Oliver Distler Speakers bureau: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Carlo Vinicio Caballero: None declared, Carlos Enrique Toro Gutierrez: None declared, Dey Dzifa: None declared, Ashima Makol: None declared, Ai Lyn Tan Speakers bureau: Has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Samuel Katsuyuki Shinjo: None declared, Vishwesh Agarwal: None declared, Latika Gupta: None declared.
ABSTRACT
COVID-19, which infects millions of people worldwide, can affect many organs and systems, mainly the lungs, heart, brain, kidneys, vascular endothelium and bone marrow. As a result, it causes a wide range of complications such as ARDS, acute coronary syndrome, delirium, pancytopenia, DIC, kidney damage. There-fore, in the presence of COVID-19, some diseases that progress rapidly and which can cause similar complications may be concealed. In our article, we aimed to describe a patient who was missed due to the adverse effects of the pandemic period and because the COVID-19 infection may cause similar findings, although he admitted to emergency clinic twice before. In a pancytopenic patient suffering from intermittent fever, exhaustion, myalgia and arthralgia for several months, the diagnosis of small cell lung cancer, bone marrow metastasis and Lambert Eaton Myasthenic Syndrome (LEMS) was delayed due to the presence of COVID-19 infection. Therefore, the patient died in a short time. It was presented because it is a rare case and can lead to serious consequences if not imagined.Copyright © 2021, Derman Medical Publishing. All rights reserved.
ABSTRACT
As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases.
ABSTRACT
Background/Aims Adult-onset Still's disease is a systemic inflammatory disease of unknown aetiology. Post-COVID-19 vaccine adult-onset Still's disease has been reported and was associated with only mild myocarditis. Here we report the first case of adult-onset Still's disease after mRNA COVID-19 vaccination presenting with severe myocarditis with acute heart failure and cardiogenic shock. Methods We described the case history of the patient. Results A 72-year-old Chinese woman developed gradual onset of fever, shortness of breath, sore throat, generalised arthralgia, malaise and poor appetite 15 days after receiving the first dose of BNT162b2 mRNA COVID-19 vaccine. Physical examination revealed fever, bilateral ankle oedema and elevated jugular venous pressure. Significant investigation results are shown in Table 1. Extensive viral panel tests (including enterovirus, influenza and cytomegalovirus) were all negative. Echocardiography showed severely reduced left ventricular ejection fraction of 20%. The acute heart failure was complicated by cardiogenic shock requiring intensive care unit admission. Myocarditis was later diagnosed. Although the heart condition subsequently improved, there were persistent fever and arthralgia, as well as the development of generalised maculopapular skin rash. In view of that, series of investigations were performed, which revealed persistent neutrophilic leucocytosis, hyper-ferritinaemia and liver function derangement, while autoimmune panel was grossly unremarkable and septic/viral workup was negative (Table 1). Contrast PET-CT scan showed no features of malignancy. Adult-onset Still's disease was diagnosed, and the patient was treated with oral prednisolone 40mg daily. The patient's condition responded to the treatment;the fever subsided and the leucocyte count and inflammatory markers were normalised, and she was subsequently discharged. Three months after discharge, the patient was clinically well with prednisolone tapered down to 5mg daily. Reassessment echocardiogram showed full recovery with LVEF 60%. Conclusion Severe myocarditis with acute heart failure and cardiogenic shock is a possible initial presentation of adult-onset Still's disease after mRNA COVID-19 vaccination. After exclusion of more common aetiologies, it is important to consider adult-onset Still's disease as one of the differential diagnoses in the presence of compatible features following COVID-19 vaccination, such that appropriate and timely workup and treatment can be offered. (Table Presented).
ABSTRACT
Background: We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, nose, anosmia, hyposmia, smell, olfactory, ORL, different ENT related symptoms. We reviewed published and peer-reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. Main text: Within the included 2549 COVID-19 laboratory-confirmed positive patients, smell affection was reported in 1453 patients (57%). The other reported ENT manifestations were taste disorder (49.2%), headache (42.8%), nasal blockage (26.3%), sore throat (25.7%), runny nose or rhinorrhea (21.3%), upper respiratory tract infection (URTI) (7.9%), and frequent sneezing (3.6%). Conclusion(s): Smell affection in COVID-19 is common and could be one of the red flag signs in COVID-19 infection. With a sensitivity of utilized questionnaire in smell identification, a homogenous universal well-defined COVID-19 questionnaire is needed to make the COVID-19 data collection more sensible.Copyright © 2021, The Author(s).
ABSTRACT
Objectives: To evaluate the association between the ABO and Rh antigens and the clinical characteristics and evolution of the SARS-CoV-2 infection in patients with rheumatic diseases. Method(s): SAR-COVID is a national, longitudinal, and observational registry. Patients >=18 years of age with a diagnosis of inflammatory or degenerative rheumatic disease, and confirmed SARS-CoV-2 infection (RT-PCR or serology) were included. Data were collected from August 2020 to June 2022. Sociodemographic, clinical data, comorbidities, underlying rheumatic disease, disease activity, and its treatment at the time of infection were recorded, aswell as symptoms, complications and treatments received for COVID-19. The WHO ordinal scale (WHO-OS) was used, and severe COVID-19was defined as WHO-OS>=5. Patients were categorized as follows: blood group A or non-A, and Rh factor positive or negative. Result(s): A total of 1356 patients were included, 547 (40,3%) had blood group A and 809 non-A (59,7%). Regarding the Rh factor, 1230 (90,7%)were positive and 126 (9,3%) negative. Age, sex, ethnicity and comorbidities were comparable between both groups. In both cases, the most frequent rheumatic diseases were rheumatoid arthritis (38,9%;p = 0,052), systemic lupus erythematosus (17,4%;p = 0,530) and osteoarthritis (10,1%;p = 0,888). Patients with non-A blood type presented a higher frequency of psoriatic arthritis (group A 5,1% vs non-A 8,7%;p = 0,015). During SARS-CoV-2 infection, more than 90% of patients in both groups were symptomatic (group A 96.0% vs non-A 94,8%;p = 0,384). Non-A blood group patients had a significantly higher frequency of arthralgia and dysgeusia. In A blood group 18.5% of the patients required hospitalization, 41,0% of them were admitted in the intensive care unit and 5.9% presented complications, while in the non-A blood group, were 16,7%, 31,1% and 5,5%, respectively (p > 0,05 in all the cases). The most frequent complications in both groups were respiratory distress syndrome and sepsis (p > 0,05). The outcome of the COVID-19 infection is detailed in Figure 1. In the multivariate analysis, adjusted for poor prognostic factors, patients with A blood type and those with negative Rh factor presented more likely severe COVID-19. (OR 1,75, 95%CI 1,20-2,56, p = 0,003 and OR 2,63, 95%CI 1,45-4,55, p = 0,001, respectively). Conclusion(s): Blood type A and negative Rh factor were associated with worse COVID-19 outcomes in this national cohort of patients with rheumatic diseases.
ABSTRACT
Objectives: To evaluate the safety and immunogenicity of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with Rheumatoid Arthritis (RA). Method(s): These data are from the 'SAFER (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases)' study, a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 vaccine in immunomediated rheumatic diseases (IMRDs). Adverse events (AEs) in patients with RA were assessed after two doses of ChAdOx1 or CoronaVac. Stratification of postvaccination AEs was performed using a diary, filled out daily. The titers of neutralizing antibodies against the receptor-biding domain of SARS-CoV-2 (anti-RBD) were measured by chemilumine scence test after each dose of immunizers. Proportions between groups were compared using the Chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test. Result(s): A total of 188 patients with RA were included in the study, most of them were female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed. The more common AEs after the first dose were pain at injection site (46,7%), headache (39,4%), arthralgia (39,4%) and myalgia (30,5%), and ChAdOx1 had a higher frequency of pain at the injection site (66% vs 32 %, p alpha 0.001) arthralgia (62% vs 22%, p alpha 0.001) and myalgia (45% vs 20%, p alpha 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection site (37%), arthralgia (31%), myalgia (23%) and headache (21%). Arthralgia (41,42 % vs 25 %, p = 0.02) and pain at injection site (51,43% vs 27%, p = 0.001) were more common with ChAdOx1. No patients had a flare after vaccination. The titers of anti-RBDafter two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p alpha 0,001). Conclusion(s): The frequency of local adverse effects, particularly pain at injection site, was high. AEs were more frequent with ChAdOx1, especially after the first dose. The use of the immunizers dis not change the degree of inflammatory activity of the disease. In patients with RA, ChAdOx1 was more immunogenic than CoronaVac. .
ABSTRACT
Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease which presents infections as one of the most frequent complications, including more severe outcomes of Coronavirus disease 2019 (COVID-19). Immunization of these patients has been strongly recommended, however, data on safety are still scarce. In this study we evaluate the safety after vaccination against SARS-CoV2 in patients with SLE. Method(s): Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease - the 'SAFER' study, is a longitudinal Brazilian multicenter phase IV study. In this study patients with SLE (according to the 2019 ACR/EULAR criteria), older than 18 years who received vaccination against SARS-CoV-2 CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) were included. The evaluation of adverse events (AEs) was done by telephone contact, symptom diaries and a face-to-face visit on the 28th day after each dose. Patients were followed up also by disease activity, assessed using SLEDAI-2 K score. Result(s): A total of 367 individuals with SLE were included, 207 received CoronaVac, 128 received ChadOx-1 and 32 received BNT162b2. Ninety percent of the subjects were female with a mean age of 37 years. About 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38%(140) of patients had zero SLEDAI-2Kat baseline and 41%(147) had zero SLEDAI-2 K 28 days after the 2nd dose. After the first and second dose the most frequent AEs were pain at injection site (58%/44%), headache (48%/33%) and pruritus (42%/37%). Comparing the three vaccines, after the first dose, local symptoms, myalgia, and fever were less frequent in patients who received CoronaVac (p alpha 0.001) as well as headache, tiredness (p = 0.001) and arthralgia (p = 0.003). After the second dose, only local symptoms such as pain at the application site and thickening of the skin around the application site were less frequent in the CoronaVac group (p alpha 0.05). Headache, tiredness, musculoskeletal symptoms and fever were more common in patients receiving AstraZeneca. No serious adverse events were reported regardless of the vaccination schedule used. Conclusion(s): This study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Neither severe AEs were reported nor worsening of disease activity were reported. Comparing the different vaccines, CoronaVac had fewer adverse events.
ABSTRACT
Introduction: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission atWeek (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IV->GUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. AtWk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6 % (29/105) of patients randomized to PBO IV (both p< 0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response atWk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar toWk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified. (Figure Presented).