EVALUATION OF RESPONSE TO ADJUVANTED RECOMBINANT ZOSTER VACCINATION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB: RESULTS FROM A RANDOMIZED TRIAL SUB-STUDY

BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.

SAFETY OUTCOMES IN PATIENTS (PTS) WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH FILGOTINIB (FIL) IN FILOSOPHY: INTERIM RESULTS FROM A PROSPECTIVE OBSERVATIONAL STUDY

BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS  vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.

PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

EFFICACY AND SAFETY OF DAZODALIBEP (VIB4920/HZN4920) IN SUBJECTS WITH SJÖGREN'S SYNDROME: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY

BackgroundSjögren's syndrome (SS) is a chronic, systemic autoimmune disease affecting exocrine glands, primarily the salivary and tear glands, with potentially severe manifestations in multiple organs. No approved disease-modifying therapies exist. Dazodalibep (DAZ) is a biologic antagonist of CD40L.ObjectivesThe objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity (NCT04129164).MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity, as defined by a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Eligible subjects were randomized 1:1 to receive intravenous DAZ 1500 mg or placebo (PBO) Q2W x 3 doses, then Q4W x 4 additional doses. Starting on Day 169, subjects initially randomized to DAZ received PBO Q4W x 5 doses and subjects randomized to PBO received DAZ Q4W x 5 doses and were then followed for 12 weeks. The primary endpoint was the change from Baseline in ESSDAI at Day 169. Safety assessments included the incidence of adverse (AEs), serious AEs (SAEs), and AEs of special interest (AESIs).ResultsThe 74 randomized subjects all received ≥1 dose of study medication (DAZ, N=36;PBO, N=38). The baseline demographics and disease characteristics were balanced between the two groups. The change from Baseline to Day 169 in ESSDAI score (LS mean ± SE), was -6.3 ± 0.6 in DAZ-treated subjects compared to -4.1 ± 0.6 in the PBO group, a difference of -2.2 (p = 0.0167). Compared to the PBO group, the DAZ group showed positive trends in the EULAR Sjögren's Syndrome Patient Reported Index score, and Functional Assessment of Chronic Illness Therapy-Fatigue score at Day 169. A post-hoc responder analysis of subjects achieving high levels (5 and 6 points) of improvement on ESSDAI favored DAZ (61.1% and 60.0%) over PBO (35.1% and 34.3%).The reported AEs were generally mild through Day 169 and similar in frequency between treatment groups. The most frequently reported AEs occurring in ≥5% of DAZ-treated subjects and >PBO were COVID-19, diarrhea, dizziness, ligament sprain, upper respiratory tract infection, contusion, device allergy, fatigue, hypertension, and oropharyngeal pain. Two SAEs were reported in a single DAZ-treated subject: this subject was a 59-year-old female who experienced a grade 3 SAE of COVID-19 infection and later died of unknown cause 46 days after last administration of DAZ (12 days after COVID-19 diagnosis). There was a single AESI of herpes zoster in a DAZ-treated subject.ConclusionDAZ is a potential new therapy for the treatment of systemic disease activity in patients with SS. SS subjects with moderate-to-high systemic disease receiving DAZ experienced a statistically significant reduction in disease activity relative to PBO as measured by the improvement in ESSDAI score. Except for a case of severe COVID-19 infection, DAZ therapy in SS subjects appeared to be well tolerated. Larger controlled trials of DAZ therapy for SS are warranted to further explore its safety profile and confirm its clinical efficacy.Table 1.Efficacy and Safety DataPBO N=38DAZ 1500 mg N=36EfficacyΔESSDAI, LS mean (SE) †-4.1 (0.6)-6.3 (0.6)*ΔESSPRI, LS mean (SE) †-1.12 (0.29)-1.80 (0.31)ΔFACIT-Fatigue, LS mean (SE) †5.8 (1.6)8.1 (1.6)AE Summary, n (%)≥1 AE23 (60.5)28 (77.8)≥1 related AE8 (21)10 (27.8)≥1 SAE01 (2.8)≥1 related SAE00≥1 AE leading to discontinuation00≥1 AESI01 (2.8)≥1 Death01 (2.8)Efficacy endpoints as of Day 169;† Analyzed using MMRM;Comparisons vs PBO;*p<0.05;AE summaries based on AEs that occurred through Day 169;AE, adverse event;AESI, adverse event of special interest;ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index;ESSPRI, EULAR Sjögren's Syndrome Patient Reported Index;FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue;PBO, placebo;SAE, serious adverse eventFigure 1.AcknowledgementsFunded by Horizon herapeutics. Medical writing support provided by B Lujan, PhD, an employee of Horizon Therapeutics.Disclosure of InterestsE. William St. Clair Consultant of: Horizon Therapeutics, Bristol Myers Squibb, CSL Behring, Resolve Therapeutics, Sonoma Biotherapeutics. Royalties: UpToDate, Liangwei Wang Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Ilias Alevizos Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, William Rees Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Alan Baer Consultant of: Bristol Myers Squibb, Wan Fai Ng Consultant of: Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Janssen and UCB, Ghaith Noaiseh Consultant of: Novartis, Chiara Baldini Consultant of: GSK, and Sanofi.

Three clinical cases of herpes zoster after vaccination against COVID-19 in active athletes. - Bulgarian medical journal, 2023, 17(1), 67-70

Shingles is a viral skin disease caused by the Varicella Zoster virus. We report varicella zoster virus reactivation in three long-time athletes after vaccination with a COVID-19 mRNA vaccine. The three athletes had no evidence of immunosuppressive conditions or other illnesses, and all three did not suffer from COVID-19. The first patient is a 21-year-old athlete with an 8-year sports career. He developed shingles four days after being vaccinated against COVID-19. The second athlete is 20 years old and has been actively involved in fitness for ten years. He was diagnosed with herpes zoster three days after the vaccination. The third athlete is 23 years old and has been actively involved in sports and fitness since the age of 6;he was diagnosed 4 days after the vaccination against COVID-19. All three were diagnosed by a dermatologist. Discussion: The relationship between the development of herpes zoster after the administration of a vaccine against COVID-19 has been the subject of many studies worldwide, but the occurrence of herpes zoster after Covid-19 vaccination in athletes is described for the first time. Our team did not find a report of a case of an athlete with herpes zoster after vaccination for COVID-19 anywhere, which motivated us to describe the above three cases.

LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1 [1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt's assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15 (Table 1). The overall UPA safety profile remained unchanged (Figure 1) [1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a (n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/ 48.263.1/54.1*/ 35.787.9/74.4/ 47.861.1/46.6/ 28.786.2/65.2/ 39.8Minimal disease activity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/ 43.458.1/46.7/3 7.678.6/63.5/ 50.954.0/40.8/ 30.379.6/59.9/ 44.6Resolution of enthesitis by Leeds Enthesitis Indexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds Dactylitis Indexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire- Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt's assessment of pain (numeric rating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease Activity Indexf-3.09-3.27-3.16-3.54-2.81-2.71Modified total Sharp/van der Heijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104);data are presented by originally randomized group. bPts with psoriasis affecting ≥3% of body surface area at BL. cPts with LEI >0 at BL;resolution LEI=0. dPts with LDI >0 at BL;resolution LDI=0. eData shown as MMRM (least squares mean) and AO (mean). fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria;ADA, adalimumab;AO, as observed;BL, baseline;MMRM, mixed effect model repeated measurement;NRI, non-responder imputation;PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index;pt, patient;UPA15/30, upadacitinib 15/30 mg once daily;wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB;and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

SAFETY ANALYSIS OF JAKINIBS IN REAL CLINICAL PRACTICE IN A COHORT OF 116 PATIENTS

BackgroundJanus kinase inhibitors (JAKinibs) have demonstrated efficacy in the treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA), although their safety profile continues to be analysed due to the possible increase in adverse events (AEs) in relation to anti-TNFs (mild and severe infections, haematological alterations, thromboembolism, increase in neoplasms).ObjectivesTo evaluate in real clinical practice the AEs of JAKinibs in a cohort of patients with RA and SpA. In addition, adherence and reasons for discontinuation (1st or 2nd failure, AE) are analysed.MethodsObservational study of 116 patients diagnosed with RA or SpA who received treatment with JAKinibis (tofacitinib, baricitinib, upadacitinib) after failure of treatment with different classical synthetic (FAMEsc) or biological (FAMEb) disease-modifying drugs. The following data were analysed: demographic characteristics of the patients, years of disease progression, 1st or 2nd failures and AE.ResultsMean age was 52 years, with Baricitinib being older (60 years -SD 13.6), higher prevalence of females in all groups, and a disease progression time of about 10 years. Mean number of FAMEsc was 1.6 and mean number of FAMEb was 2,3 to Tofacitinib(Tofa), 2,76 to Baricitinib(Bari) and 4,4 to Upadacitinib(Upa). 71 (63%) patients had active corticosteroid therapy. The median treatment time with Tofa was 8.8 months, Bari 9.5 and Upa 2.4 months.Most frequent AEs with Tofa were urinary tract infections(UTI) (11.9%, 7 cases) and headaches (8.47%, 5 cases). There were 3 cases of herpes zoster (5.1%), one of which was recurrent, and 2 cases respectively of tachycardia and gastrointestinal intolerance (3.4%). With Baricitnib, 2(5%) cases of UTI and 2(5%) of influenza A were reported. Most frequent AEs related to Upadacitinb are gastrointestinal intolerance, labialis and facial herpes, anterior uveitis and recurrent UTI, with 1 case for each adverse event. There were 4 success with Baricitinib treatment: 2 due to severe COVID, 1 influenza A and 1 due to stroke. 17 patients had 1st failure to Tofa(28.81%), 8 to Bari20.0%) and 3 to Upa(18.75%);7(11.86%) and 2(5%) patients had 2nd failure to Tofa and Bari respectively, no with Upa.Mean CRP to Tofa-SD 18.9-was 17.19, 20-SD 22.7- to Bari and 24.2-SD 27.40- to Upa. Mean ESR-SD 15.3- was 25.4, -SD 26.4 and 44.3 -SD 32-, respectively. At 6 months, 36(62%) were continuing on Tofa, 22(56%) on Bari and 4(27%) on Upa. At 12 months, 27(46.6%) were still on Tofa and 12 on Bari(30.8%) and no patients were on upa.Table 1.TofaBariUpaMean age496047Male19%18%20%Female81%82%80%Time course of disease(years)81111Permanence 6 months62%56%27%Permanence 12 months46,6%31%0%Patients with corticotherapy62%64%60%Previous biological drugs2,3 SD 22,8 SD 2,34,4 SD 2,9Patients who discontinued the drug62%59%33%Mean CRP at the end of treatment172024Mean end-of-treatment ESR252644Repeated AEsUTI(7) Headache(5) Shingles(3) Nephritic colic(2) Gastrointestinal intolerance(2) Tachycardia(2)UTI(4) Headache(2)Serious AEsShingles (3)Varicella encephalopathy(1) Stroke(1) Shingles (1)1st failure28,8%20%18,7%2nd failure11,9%5%0%SuccessSARS-Cov2(2) Influenza(1) Stroke(1)Figure 1. Months stay pharmacoConclusionMost frequent adverse events with JAKinibs are mild infections, except gastrointestinal complaints with upadacitinib. Serious adverse events, including 3 deaths from viral infections, were observed, mostly in patients over 65 years. Most frequent cause of discontinuation was treatment failure. We believe that further observational studies are needed to stratify and profile the risk of infection with JAKinibs.References[1]Atzeni F, Popa CD, et al. Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events. Expert Rev Clin Immunol. 2022 Mar;18(3):233-244. Doi: 10.1080/1744666X.2022.2039630 Epub 2022 Feb 17.PMID: 35129033[2]Alves C, Penedones A,et al. The Risk of Infections Associated With JAK Inhibitors in Rheumatoid Arthritis: A Systematic Review and Network Meta-analysis. J Clin Rheumatol. 2022 Mar 1;28(2):e407-e414 PMID:33902098Ackn wledgements:NIL.Disclosure of InterestsNone Declared.

Case of mixed viral infection caused by Varicella Zoster and COVID-19 in adolescents.

We report two cases of mixed infection caused by Varicella Zoster and COVID-19 in sibling adolescents. We describe the disease course and provide the results of laboratory examination. High prevalence of these infections necessitates timely verification of the diagnosis and causal therapy. Particular attention should be paid to people with a high risk of pneumonia. Timely vaccination of children against Varicella Zoster and COVID-19 is increasingly important now. The aim of this article is to draw attention to the problem of this coinfection. It allows us to accumulate the data on such cases, identify the risk factors, as well as risk factors for complications.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Comparison of laboratory parameters during herpes zoster infection: a case-control study

Objective: We aimed to find the parameters that can change during herpes zoster infection and observe the relationship of these parameters throughout the disease. Material and Methods: We compared 40 herpes zoster patients and 2 separate control groups, who were healthy and had comorbidities similar in age and gender. Patient files were retrospectively analyzed, and laboratory parameters were compared between groups. The laboratory values of the patient group with herpes zoster were evaluated among themselves according to the duration of the symptoms. Results: Fasting glucose, creatinine, aspartate aminotransferase values, the percentage and the absolute number of monocytes, red blood cell distribution width-coefficient of variation, and C-reactive protein levels of the patients with herpes zoster were significantly higher, and the absolute number of lymphocytes, mean corpuscular volume and platelet distribution width levels were lower than the control groups. The percentage of monocytes in the first 5 days was significantly higher than in the following days, and hematocrit values were lower in the last days. Conclusion: Examining routine laboratory values during diseases may help diagnose the disease, especially in patients with faint clinical signs and zoster sine zoster. In addition, it may be useful to question patients with herpes zoster for renal dysfunction, rheumatological diseases, and malignancy.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Herpes Zoster Co-Infection with COVID-19: A Case Series

Clinical presentation of COVID-19 infection can be variable in the current pandemic even in patients presenting to the clinic with a mild history of upper respiratory complaints. Various cutaneous manifestations have been noticed in COVID-19 patients with herpes zoster (HZ) being one among them. HZ is an infection that results when varicella zoster virus reactivates from its latent state in the posterior dorsal root ganglion. Here, we aim to expand our knowledge by reporting three cases of associated zoster infection in COVID-19 patients admitted to our intensive care unit in view of respiratory complaints. All the three patients admitted, had revealed lymphocytopenia at the time of HZ diagnosis, and were managed conservatively throughout the course. In all the cases, acyclovir/valacyclovir led to the resolution of lesions in 10 days. No postherpetic sequelae were observed. We here suggest that the clinical presentation of HZ at the time of the current pandemic should be considered as an alarming sign for a latent subclinical SARS CoV-2 infection and thorough follow-up of such patients be adopted.Copyright © 2021 Bali Journal of Anesthesiology. All rights reserved.

Can the COVID-19 Vaccine Cause Recrudescence of Herpes Zoster Virus While Taking Antiviral Medication?

Coronavirus disease 2019 (COVID-19) represents a multisystem disease that has caused a devastating global pandemic. The COVID-19 vaccine produced in response to the pandemic has been effective but can have side effects. One well-established condition is the reactivation of herpes zoster (HZ). Various risk factors increase the risk of HZ reactivation such as age, infections, and immunosuppressed states. HZ can have severe complications, including herpes zoster ophthalmicus and postherpetic neuralgia. Here, we present a unique case where a patient experienced HZ reactivation after both primary doses of the COVID-19 vaccine despite receiving early antiviral treatment.

Herpes Zoster Virus Reactivation in a 16 Year Old Female Post COVID-19 Vaccine. Case report and Review of the Literature.

Background: According to WHO, there have been 9205 fatal COVID-19 cases confirmed in Saudi Arabia out of 793,729 cases overall (5). During the development of COVID-19 vaccines, several technologies were used including DNA-based, RNA-based vaccines, non-replicating viral vector vaccines, and inactivated vaccines. Objective: We present a case of varicella zoster virus reactivation post COVID-19 vaccine in a young medically free 16 years old female and review of the literature using the keywords "Herpes Zoster, "varicella zoster"," shingles", "post COVID-19 vaccine", "Post COVID-19 cutaneous manifestations". Methods: The search was conducted in Google Scholar, Scopus, PubMed, and Web of Science data bases. Results: We encountered 241 published studies in regard to post COVID-19 dermatologic manifestations including post COVID-19 vaccine herpes zoster reactivation in the English literature and one case in German. Our case and 4 other reported cases in the literature are patients aged of 20 years old and below. Conclusion: Varicella zoster virus falls under the family of Herpesviridae, It's characterized by its ability to escape host immune system and remain dormant in ganglionic neurons. Reactivation of the infection will result in herpes zoster manifesting as painful vesicles in a dermatomal distribution. Possible link is the suppression of type-one interferons caused by the mRNA-based vaccine such as COVID-19 vaccines. Yet, potential correlation remains to be demonstrated.

Long-Term Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis Refractory to Biologic Therapies: 2-Year Results from the Phase 3 Select-Psa 2 Study

Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.

Herpes zoster – Part 3: Prevention of herpes zoster and post-herpetic neuralgia

Vaccination recommendations for the prevention of herpes zoster (HZ) aim to reactivate specific cell-mediated immunity towards the varicella/zoster virus. This specific immunity naturally declines with age but there are many factors that can accelerate this decline, including, most recently, the immune response induced by SARS-CoV-2. Two vaccines are available to date. A live attenuated vaccine (Zostavax®) licensed in 2006 and more recently a recombinant vaccine (Shingrix®). We present data on the efficacy of these two vaccines as well as on the relevant precautions and safety of use. © 2023 Elsevier Masson SAS Les recommandations vaccinales en matière de prévention du zona ont pour objectif de réactiver l'immunité à médiation cellulaire spécifique contre le virus varicelle-zona. Cette immunité spécifique décline naturellement avec l'âge mais nombreux sont les facteurs qui peuvent accélérer ce déclin dont récemment la réponse immunitaire induite par le SARS-CoV-2. Deux vaccins sont disponibles à ce jour : un vaccin vivant atténué (Zostavax®) homologué en 2006 et plus récemment un vaccin recombinant (Shingrix®). Nous présentons des données d'efficacité de ces deux vaccins ainsi que celles concernant leurs précautions d'emploi et la sécurité de leur utilisation. © 2023 Elsevier Masson SAS

An Emerging Role of Interferon Targeted Therapy in Mucocutaneous Sle: A Prospective Real-World Evaluation of Anifrolumab for Refractory Cutaneous Lupus

Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300mg by monthly iv infusion) following application to the manufacturer's early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI);Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n=5, chilblain LE n=1, subacute cutaneous LE n=1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26;higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved >=75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p<0.001) and EQ5D-VAS (p=0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p=0.01) and pain (p=0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients.

Janus Kinase Inhibitors in Rheumatoid Arthritis Patients: Real-World Experience from a Regional Centre in Uk

Background/Aims Tofacitinib and baricitinib were the first orally available, targeted synthetic Janus kinase (JAK) inhibitors approved for the treatment of rheumatoid arthritis (RA) in the UK. Evidence suggests that JAK inhibitors are as efficacious as biological DMARDs in the treatment of RA. Their safety profile has been demonstrated in long term extension studies and RCTs. However, real-world, long-term data remains as important in bridging the gap between controlled studies and routine practice. We report our initial real-world experience of a cohort of RA patients commenced on JAKi before the SARS-CoV-2 pandemic within a regional centre in the UK. Methods All patients commenced on JAKi for the treatment of RA between February 2018 and March 2020 were identified from our in-house database. Data was retrospectively collected from clinical notes and electronic health records from February 2018 up until April 2022. This included patient demographics, disease duration, serological status, concurrent csDMARD usage, history of bDMARD exposure, duration of use and reason for discontinuation of the drug if appropriate. DAS- 28 scores were recorded at baseline and quarterly. SPSS (version 22.0) was used for data analysis. Results One hundred thirty patients were treated with JAK inhibitors (Tofacitinib 22%, Baricitinib 78%);80% female, mean (S.D.) age 61.5 (12.3) years. 92 (70.8%) patients were seropositive. 70 (53.8%) patients were on concurrent csDMARDs and 23 (17.7%) on concurrent steroids. The mean number of previous bDMARDs was 1.8 +/- 1.7;41 (31.5%) were bDMARD naive. The mean baseline DAS-28 ESR (S.D.) score was 5.96 (0.96). There were significant differences in mean DAS- 28 ESR scores (compared with baseline) of 1.54, 1.96, 2.41, 2.33 and 1.80 at 3, 6, 12, 18 and 24 months respectively (p<0.0001). Mean DAS-28 ESR scores were not statistically significant between bDMARD naive patients and those that had previously received bDMARDs. Overall JAKi retention rate was 66.9% with a mean follow up duration of 27.4+/-13.1 months. Persistence was 88.5%, 76.9%, 73.2% and 68.5% at 6, 12, 18, and 24 months, respectively. Of the 38 patients who stopped JAK inhibitors, 11 stopped due to inefficacy (6, primary inefficacy). 3 patients were lost to follow-up and 6 deceased. Cause of death was sepsis (2), venous thromboembolism (1) and unknown (3). 18 patients stopped because of adverse events (AEs). The most common AEs were recurrent infections (11), gastrointestinal side effects (9), lymphopenia (7), thromboembolic events (6) and herpes zoster (5). In total 6 (4.1%) patients had thromboembolic events which included pulmonary embolism (4) and deep vein thrombosis (1) and central retinal artery thrombosis (1). Conclusion JAK inhibitors in this real-world population of RA patients were effective in reducing disease activity and patients had high persistence rates. Recurrent infections, herpes zoster and thrombo-embolism remain adverse events of concern.

Rheumatologistadherence to Vaccine Recommendation in Patients with Immune-Mediated Inflammatory Diseases

Objectives: Backgroud: Patients with immune-mediated inflammatory diseases (IMID), have an increased risk of presenting infections, this arises from immunosuppression related to the disease and its treatments. Vaccination in patients with autoimmune diseases is highly recommended by various clinical practice guidelines(1). Studies in Latin America show low rates of adherence, both in patients vaccine application and doctor's recommendations. One study shows that the lack of vaccination in 43% of their patients was due to their rheumatologist not recommending it (2). This is an eye opener on the key role physicians play in the overall outcome. Objective(s): To determine the adherence rate rheumatologists have, when it comes to recommending their patients vaccinations, suggested by clinical practice guidelines. Method(s): A descriptive study was performed, with previous authorization by the research department of the Colombian rheumatology association (ASOREUMA). A survey was sent via email to all its members asking about general knowledge about the subject and percentages on recommendations in their daily practice. Result(s): The survey was sent to 214 rheumatologist members of ASOREUMA, 34 (16%) of whom responded. In clinical practice there is a universal knowledge on the vaccination requirements for patients with IMID, nevertheless just 38.2% of clinicians tell patients to vaccinate against influenza of the 80%-100% of patients they see. For pneumococcus its 26.5%, hepatitis B 20.6%, human papilloma virus 8.8%, herpes zoster 2.9%. When it comes to SARS CoV2 vaccines it's by far the most recommended with 79.4%, and most physicians consider its mechanism of action before prescribing it. In table 1 we are summarizing the primary results. Conclusion(s): Despite the fact that rheumatologists are widely aware of the indications for vaccination in patients with IMID, these recommendations are not transmitted to all patients, due to the limited care time for each patient;in addition to the fact that the vast majority consider that the health system does not allow quick and timely access to these services.

Pole-to-pole involvement of varicella zoster virus reactivation following COVID-19 vaccination.

The aim of this study is to report the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management outcomes in a series of three cases of varicella zoster virus (VZV) reactivation following one dose of coronavirus disease 2019 (COVID-19) vaccination. This was a retrospective and observational study. All the patients who developed uveitis post-vaccination were pooled together. Patients who had VZV reactivation were included. Two cases had polymerase chain reaction positive for VZV from aqueous humor. At the time of presentation, IgG and IgM spike protein antibodies for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were tested. Out of this pool, three patients with classical features to describe pole-to-pole manifestations were chosen. A 36-year-old lady with post-vaccination sclerokeratouveitis associated with reactivation of herpes zoster ophthalmicus, a 56-year-old lady with post-vaccination acute anterior uveitis associated with herpes zoster ophthalmicus, and a 43-year-old gentleman with post-vaccination acute retinal necrosis were included. We present a possible link between anti-SARS-CoV-2 virus vaccination and varicella zoster reactivation in these patients and also describe the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management with detailed discussion.

Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license