ABSTRACT
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.
ABSTRACT
Introduction: Per WHO, >190 million people worldwide have been affected by COVID-19 as of 20-Jul-2021. Although people with MS are not at a higher risk of SARS-CoV-2 infection, factors such as age, comorbidity, MS severity and treatment with DMTs may affect COVID-19 severity and outcomes. Understanding the risks, severity and outcomes of COVID-19 in people with MS receiving DMTs, including anti-CD20 DMTs, is important to healthcare practitioners (HCPs) managing MS. Objectives: To report the characteristics and outcomes of COVID- 19 adverse events (AEs) in relapsing MS (RMS) patients taking ofatumumab enrolled in the ongoing, open-label, long-term extension Phase 3b ALITHIOS study and from post-marketing surveillance of people receiving ofatumumab 20 mg subcutaneously. Methods: Patient demographics, baseline characteristics, incidence of COVID-19 AEs, seriousness category (including hospitalization), severity, outcomes, ofatumumab exposure before the start of infection, and action taken with ofatumumab were assessed. Results: As of 29-Jan-2021, 139/1703 (8.2%) patients enrolled in ALITHIOS (mean±SD age at baseline: 37.7±8.7 years;female, 64%) treated with ofatumumab reported COVID-19 AEs (confirmed: 115 [82.7%];suspected: 24 [17.3%]). Of these, 10 (7.2%) experienced COVID-19 serious AEs and all 10 (7.2%) were hospitalized. Most AEs reported were mild (Grade [G] 1;69 [49.6%]) or moderate (G2;62 [44.6%]) in severity. Severe (G3) and life threatening (G4) AEs were reported in 6 (4.3%) and 2 (1.4%) patients, respectively. One (0.7%) patient (48-year-old at COVID- 19 onset;BMI 28.3 kg/m2;recent MS relapse) with confirmed COVID-19 and pneumonia had a fatal outcome. At data cut-off, most patients (128 [92.1%]) had recovered from COVID-19 AEs;2 (1.4%) were recovering, 4 (2.9%) had recovered with sequelae and 4 (2.9%) had not recovered. COVID-19 AEs led to temporary interruption of ofatumumab in 22 (15.8%) patients. As of 31-Jan- 2021, an additional 28 RMS patients with COVID-19 AEs were identified in the Novartis safety database. Further details to be presented. Conclusions: In ALITHIOS, 139 RMS patients on ofatumumab reported COVID-19 AEs (as of 31-Jan-2021). Most (94%) COVID-19 cases were mild or moderate in severity. There were few hospitalizations but one fatal outcome. At data cut-off, most (92%) patients had recovered/resolved from COVID-19. ALITHIOS data extends the understanding of the long-term safety profile of ofatumumab in people living with MS.
ABSTRACT
Objective: Report characteristics of COVID-19 infections in people with multiple sclerosis (pwMS) receiving subcutaneous 20mg of atumumab, a human anti-CD20 monoclonal antibody, every 4 weeks. Background: A global pandemic of COVID-19 has resulted in over 40 million cases as of 19 October 2020. Risks of COVID-19 in pwMS receiving disease-modifying therapies are of increased interest, but still under investigation. Design/Methods: Demographics, COVID-19 seriousness category, of atumumab treatment duration and action taken with of atumumab, interventions and COVID-19 outcomes were recorded for pwMS in the open-label extension study ALITHIOS or in the post-marketing setting. Results: As of 28 September 2020, 12/1623 pwMS (5/12 females;9/12 white) in the ALITHIOS study were reported to have laboratory-confirmed SARS-CoV-2 infection. Mean age was 37.8 years (median 44 years, range 25-51 years), disease duration 3 to 23 years, and EDSS score 0-5.5. Ofatumumab exposure range was 8.5-13.8 months (n=6 who received of atumumab only in ALITHIOS) and 17.4-44.2 months (n=6 who continued of atumumab from prior trials). One of 12 had COVID-19 seriousness grade 3-A 39 year old white male with bilateral pneumonia requiring hospitalization who recovered with normal follow-up chest X-ray. The remaining 11 cases were non-serious grades 1 or 2: Seven reported as completely recovered, one recovering, two as ongoing and one asymptomatic with SARS-CoV-2 IgM and IgG positive. Six patients were treated with anti-infectives (three received both antivirals and antibacterials and three received antibacterials). Ofatumumab treatment was unchanged in seven and interrupted in four (resumed in three;information not available for one) patients;action unknown in one. To date, no post-marketing COVID-19 cases have been reported. Conclusions: We report 12 cases (11 non-serious;one serious hospitalized for bilateral pneumonia) of laboratory-confirmed SARS-CoV-2 infection in pwMS treated with of atumumab. More surveillance data are needed to determine the risks associated with COVID19 in pwMS treated with of atumumab.
ABSTRACT
Objective The COVID-19 pandemic has infected over 870,000 Canadians and caused 22,000 deaths. Many patients are attempting to balance health and financial stability. Therefore, we sought to determine how physicians who frequently prescribe immunosuppressive medications are counselling patients on return-to-work prior to widespread vaccine distribution and understand their decision processes. Methods We administered a survey through the Canadian Rheumatology, Gastroenterology and Dermatology Associations. Physicians were asked whether patients have requested counselling on return-to-work during the pandemic and how they decide what advice to provide. They were shown seven clinical scenarios of patients on immunosuppressive medications, then asked whether they would provide a medical note advocating for delayed return-to-work or modified duties to reduce exposure. Results 151 physicians took the survey. 94% were asked for advice on return-to-work. 33% felt informed enough to provide counselling. When patients requested a medical note, physicians provided one 25% of the time. Factors most associated with providing notes were patient comorbidities, age, glucocorticoids, high risk work and vulnerable co-inhabitants. Conventional synthetic and biologic immunosuppressants did not prompt most physicians to provide a note. Respondents considered patient perspectives and workplace factors. Several requested guidelines to approach these encounters. Conclusion Almost all rheumatologists, dermatologists and gastroenterologists have been asked to counsel patients on returning to work during the COVID-19 pandemic. Most do not feel informed enough to do so. Medical notes for acconunodations are only provided a minority of the time, unless specific factors (e.g. glucocorticoids) are present. Guidance is needed to inform these decisions.
ABSTRACT
Background: While some risk factors for severe COVID have been identified for patients with rheumatic diseases,1 few studies have investigated whether outcomes differ based on the type of rheumatoid arthritis (RA) treatment. Most existing reports have been limited to individual centers or voluntary reporting registries.2,3 Objectives: To compare the occurrence of hospitalizations following COVID-19 diagnosis among patients with RA treated with various classes of DMARDs. Methods: A cohort of patients with confirmed COVID-19 (ICD10 diagnosis code or positive PCR or antigen test result) were identified within a large US electronic health record (EHR) dataset (Optum, Inc.) during the time period Feb 1, 2020 through Oct 14, 2020. From these, we identified RA patients (ICD10 RA diagnosis code) with treatment (most recent of JAK inhibitor [JAKi], biologic [bDMARD] or conventional synthetic [csDMARD] only) within the 12 months prior to COVID-19 diagnosis (i.e., index). The primary outcome was any hospitalization on or within 30 days after COVID-19 diagnosis. Multivariable logistic regression models compared users of JAKi's to non-TNFi bDMARDs and csDMARDs (separately), as well as users of TNFi's to non-TNFi bDMARDS and csDMARDs (separately), and were adjusted for age, gender, index month and baseline corticosteroid use. Sensitivity analyses included restriction of prevalent treatment use to within 180 days prior to COVID-19 diagnosis and restriction of csDMARDs to a group without hydroxychloroquine or chloroquine. Results: The study included 910 RA patients on DMARD treatment who were diagnosed with COVID-19 (mean age ± SD: 61±15, 80% female, 62% white. Of those, 26% (n=240) were hospitalized on or within 30 days after COVID-19 diagnosis. The proportion of patients hospitalized was highest in non-TNFi bDMARD users (37/87;43%), followed by csDMARDs users (161/581;28%) and lowest in JAKi (13/68;19%) and TNFi users (29/174;17%). In multivariable-adjusted models, no differences in risk of hospitalization were found comparing JAKi users to csDMARD users (aOR=0.71;95% CI 0.37-1.36) or TNFi users to csDMARD users (aOR=0.67;95%CI 0.43-1.06). Compared to non-TNFi bDMARD users, JAKi use and TNFi use was associated with reduced risk of hospitalization (JAKi aOR=0.32;95%CI 0.14-0.71;TNFi aOR=0.34;95%CI 0.18-0.62). Age and corticosteroid use were positively associated with 30-day hospitalization in all models. Results of sensitivity analyses were consistent with the main findings. Conclusion: In this study, roughly a quarter of RA patients with recent DMARD treatment were hospitalized within 30 days after COVID diagnosis. Patients treated with JAKi and TNFi therapies experienced the lowest risk of hospitalization, with risk of hospitalization significantly lower than non-TNFi bDMARDs. However, recent therapy recorded in the EHR may not reflect exposure at time of COVID-19 diagnosis and small sample size per treatment may limit interpretation.
ABSTRACT
Background: Patients (pts) with rheumatoid arthritis (RA) have an increased susceptibility to seasonal influenza and its complications.1 In light of the COVID-19 pandemic, there is a need to better understand acute respiratory viral RNA infections, such as influenza, in pts with RA. Objectives: To present a comprehensive summary of data on influenza adverse events (AEs) occurring in the tofacitinib RA clinical programme. Methods: Influenza AEs were evaluated in pts with RA from 21 Phase (P)1-3b/4 trials and two open-label, long-term extension (LTE) studies from 2005-2019. These were analysed as two cohorts: P2-3b/4 cohort (pts who received tofacitinib 5 or 10 mg twice daily [BID] as monotherapy or with conventional synthetic [cs]DMARDs, adalimumab, methotrexate or placebo, in P2-3b/4 controlled studies) and Overall cohort (pts who received ≥1 tofacitinib dose, as monotherapy or with csDMARDs, in P1-3b/4 and LTE studies;data were summarised by average tofacitinib dose [average tofacitinib 5 or 10 mg BID based on average total daily dose of <15 or ≥15 mg, respectively]). Incidence rates (IRs;unique pts with events/100 pt-years of exposure;censored at day of first event or up to last dose +28 days) were evaluated for influenza AEs, influenza complication AEs, influenza-like illness (all composites of several MedDRA preferred/verbatim terms) and overall influenza AEs (composite of all preferred/verbatim terms included under influenza AEs, influenza complication AEs and influenza-like illness). In the Overall cohort, the incidence of serious non-influenza AEs within 28 days of the start of an overall influenza AE and time taken to resolution of overall influenza AEs by action taken were summarised descriptively. Results: In total, 7964 pts were included;517 (6.5%) pts reported overall influenza AEs, three of which occurred outside the risk period. In the P2-3b/4 cohort (N=6690), IRs for influenza AEs, influenza-like illness and overall influenza AEs generally appeared similar across treatment arms (Figure 1a). In the Overall cohort, IRs for influenza AEs and influenza-like illness were similar between tofacitinib doses (Figure 1b), and IRs for overall influenza AEs were similar between tofacitinib doses and pt age groups (Figure 1c). No influenza complication AEs (eg pneumonia/encephalitis influenzal) were reported in either cohort. Among pts with overall influenza AEs, nine (1.7%) had serious overall influenza AEs (average tofacitinib 5 mg BID, n=6;average tofacitinib 10 mg BID, n=3). Of these pts, eight (1.5%) were hospitalised (average tofacitinib 5 mg BID, n=6;average tofacitinib 10 mg BID, n=2) and two (0.4%) died (average tofacitinib 5 mg BID, n=1;average tofacitinib 10 mg BID, n=1). Both deaths occurred in pts with H1N1 Influenza A. Twelve (2.3%) pts had a serious non-influenza AE within 28 days of the start of the overall influenza AE (average tofacitinib 5 mg BID, n=6;average tofacitinib 10 mg BID, n=6). The most common serious non-influenza AEs (one event each in average tofacitinib 5 and 10 mg BID groups) were acute respiratory distress syndrome and pneumonia. In most pts with overall influenza AEs, no change to tofacitinib treatment was made (70.2%, n=363) or treatment was stopped temporarily (28.2%, n=146) for a mean duration of 11.0 days. The mean number of days to resolution of overall influenza AEs was numerically similar, ranging from 10.4-11.8 days across tofacitinib doses, irrespective of these actions. Conclusion: This post hoc analysis of influenza AEs across the tofacitinib RA clinical programme, over 14-15 influenza seasons, showed generally similar rates between treatment groups, and between tofacitinib doses and pt age groups. Limitations include varying exposure across treatment arms in the P2-3b/4 cohort. Most influenza AEs were non-serious (98.3%), and were not associated with changes to tofacitinib treatment.
ABSTRACT
OBJECTIVES: The COVID-19 pandemic has infected over 870,000 Canadians and caused 22,000 deaths. Many patients are attempting to balance health and financial stability. Therefore, we sought to determine how physicians who frequently prescribe immunosuppressive medications are counselling patients on return-to-work prior to widespread vaccine distribution and understand their decision processes. METHODS: We administered a survey through the Canadian Rheumatology, Gastroenterology and Dermatology Associations. Physicians were asked whether patients have requested counselling on return-to-work during the pandemic and how they decide what advice to provide. They were shown seven clinical scenarios of patients on immunosuppressive medications, then asked whether they would provide a medical note advocating for delayed return-to-work or modified duties to reduce exposure. RESULTS: 151 physicians took the survey. 94% were asked for advice on return-to-work. 33% felt informed enough to provide counselling. When patients requested a medical note, physicians provided one 25% of the time. Factors most associated with providing notes were patient comorbidities, age, glucocorticoids, high risk work and vulnerable co-inhabitants. Conventional synthetic and biologic immunosuppressants did not prompt most physicians to provide a note. Respondents considered patient perspectives and workplace factors. Several requested guidelines to approach these encounters. CONCLUSIONS: Almost all rheumatologists, dermatologists and gastroenterologists have been asked to counsel patients on returning to work during the COVID-19 pandemic. Most do not feel informed enough to do so. Medical notes for accommodations are only provided a minority of the time, unless specific factors (e.g. glucocorticoids) are present. Guidance is needed to inform these decisions.