Timely diagnosis of SARS-CoV-2 is important for infection control and treatment. Real-time reverse transcriptase PCR (rRT-PCR) tests are the reference standard for diagnosis but often require a centralized laboratory, making them time-intensive and unsuitable for resource-limited settings. The Abbott ID NOW™ COVID-19 2.0 assay is a rapid point-of-care (POC), isothermal molecular test for qualitative detection of SARS-CoV-2. We prospectively evaluated its clinical performance against three reference rRT-PCR tests: Hologic Panther Fusion, Roche Cobas, and CDC 2019-nCoV RT-PCR Diagnostic Panel. Investigators enrolled 3,530 subjects, with 3,146 evaluable. In symptomatic subjects (n = 914), the test showed a positive percent agreement (PPA) of 91.7% (95% confidence interval [CI]: 87.8, 94.4) and a negative percent agreement (NPA) of 98.4% (95% CI: 97.1, 99.1). The PPA improved with lower cycle threshold (Ct) values: 94.7% (95% CI: 91.2, 97.2) for Ct ≤36, 97.6% (95% CI: 94.5, 99.2) for Ct ≤33, and 99.4% (95% CI: 96.8, 100.0) for Ct ≤30. Discordant results were observed among the three reference rRT-PCR tests across evaluable subjects with suspected COVID-19 infection. For 1,630 cases of symptomatic and asymptomatic subjects suspected of COVID-19, where all three rRT-PCR methods were evaluable, CDC test results differed the most, with 144 discordant results with Roche and 119 with Panther rRT-PCR tests. Roche and Panther test results differed in 67 cases. In summary, the Abbott ID NOW™ COVID-19 2.0 assay can serve as a valuable diagnostic tool in acute symptomatic subjects in point-of-care settings. IMPORTANCE:The Abbott ID NOWTM COVID-19 2.0 assay is a suitable rapid test for diagnosing COVID-19 in acute symptomatic subjects and can be used in point-of-care settings and low-resource settings. With results reported in 12 minutes or less, Abbott ID NOWTM COVID-19 2.0 facilitates timely diagnosis, enabling linkage to appropriate antiviral medication.
Abstract Background/Aims For patients with RA who are refractory to biologic disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy. In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients. Objectives To describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR). Methods A post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND, -CHOICE, and -COMPARE. For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28-CRP, Clinical Disease Activity Index, and Simple Disease Activity Index, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021. Results 568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; CV risk factors were common among this refractory population. ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND and CHOICE bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups. Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 PY of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND and CHOICE bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events and venous thromboembolism, and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY. Conclusion In this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program. Disclosure R. Fleischmann: Consultancies; Consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer Inc, and UCB. Grants/research support; Grant/research support from AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and. L. Bessette: Consultancies; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. S. Hall: Consultancies; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. J. Sparks: Consultancies; Consulted for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. M. Jain: Consultancies; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. Grants/research support; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. A. Kakehasi: Consultancies; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Member of speakers’ bureau; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Grants/research support; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Y. Song: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. S. Meerwein: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. R. DeMasi: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. J. Suboticki: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. A. Rubbert-Roth: Consultancies; AbbVie, AbbVie Deutschland, Amgen, Bristol-Myers Squibb, Chugai Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen Global Services, Novartis, and Sanofi Pasteur.
Upadacitinib (UPA) a été évalué pour le traitement de la SA chez des patients (pts) naïfs de bDMARDs [1] et des pts ayant eu une réponse inadéquate (IR ; définie comme une intolérance et/ou un manque d’efficacité) aux bDMARDs (bDMARD-IR) [2]. Cette analyse post hoc a évalué l’efficacité et la tolérance d’UPA dans des sous-groupes (ss-gpes) de pts bDMARD-IR ayant une SA en fonction du traitement (ttt) antérieur. Dans l’essai de phase 3 SELECT-AXIS 2 en cours, des pts SA, bDMARD-IR et remplissant les critères de NYm (n = 420) ont été randomisés selon un ratio 1:1 pour recevoir UPA 15 mg 1x/j (n = 211) ou un placebo (PBO, n = 209) pendant 14 semaines (S). Les critères d’éligibilité incluaient un manque d’efficacité après ≥ 12S de ttt par 1 bDMARD antérieur (TNFi ou IL-17i) et/ou une intolérance à 1 ou 2 bDMARDs antérieurs, quelle que soit la durée du ttt. Un manque d’efficacité de 2 bDMARDs n’était pas autorisé. Le critère principal était la réponse ASAS40 à S14. Cette analyse post hoc a évalué à S14 et en ss-gpes en fonction du ttt antérieur, la réponse ASAS40 et les critères suivants : ASDAS-CRP LDA (< 2,1) et amélioration par rapport à l’inclusion de la douleur rachidienne évaluée par le pt, du BASFI et du SPARCC-IRM rachis. Les analyses en ss-gpes ont été réalisées en fonction du nbre (1 ou 2), du mécanisme d’action (TNFi ou IL-17i), du manque d’efficacité (TNFi ou IL-17i) et de l’intolérance (oui ou non) des bDMARDs antérieurs. Les caractéristiques à l’inclusion étaient similaires dans les gpes UPA et PBO.(2) La majorité des pts avaient été traités antérieurement par 1 TNFi (UPA : 73 %, PBO : 76 %) ; 4 % et 5 % des pts UPA et PBO, respectivement, avaient reçu 1 TNFi et 1 IL-17i. Le taux de réponse ASAS40 était plus élevé avec UPA vs PBO (Delta : 22–33 %) à S14 pour tous les ss-gpes (Fig. 1). La réponse ASDAS-CRP LDA et l’amélioration vs l’inclusion du BASFI, de la douleur rachidienne et du SPARCC-IRM rachis étaient également plus élevées avec UPA vs PBO pour tous les ss-gpes (Delta : 28–37 % ;1,0–1,6 ; 1,3–2,3 et 0,8–4,8, respectivement) (Fig. 2). Le taux d’événements indésirables (EI) était plus élevé pour UPA vs PBO indépendamment de la tolérance des bDMARDs antérieurs. Néanmoins, le taux d’EI ayant entraîné l’arrêt du ttt était similaire pour les pts ayant eu ou non une intolérance à un bDMARD antérieur (0 % vs 1,5 % et 0 % vs 1,4 %, respectivement, pour UPA vs PBO) (Tableau 1). Les taux d’EI, EI graves (EIG) et infections graves étaient plus élevés chez les pts UPA ayant eu une intolérance à un bDMARD antérieur vs ceux sans intolérance (52 % vs 36 %, 5 % vs 2 %, 20 % vs 13 % et 5 % vs 1 %, respectivement). Aucun décès n’a été rapporté. Dans SELECT-AXIS 2, UPA a démontré une meilleure efficacité par rapport au PBO à S14 pour tous les ss-gpes de pts SA bDMARD-IR. Le profil de tolérance d’UPA était cohérent avec celui de l’étude, quelle que soit la tolérance des bDMARDs antérieurs. Bien que la possibilité de conclure soit limitée par la petite taille de certains ss-gpes, le rapport B/R d’UPA était généralement favorable chez les pts SA bDMARD-IR.
Background Controlling or improving musculoskeletal disease activity of psoriatic arthritis (PsA) (eg, enthesitis and associated pain) is a treatment priority for patients, rheumatologists, and dermatologists. 1 Enthesitis is the cardinal lesion in PsA and is immunogenetically and experimentally linked to the interleukin-23 (IL-23) pathway. 2 Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits IL-23 by binding to its p19 subunit, was studied in a phase 3 adult PsA program (KEEPsAKE clinical trials). 3,4 Pooled analyses from the program demonstrated the efficacy of RZB to treat enthesitis and pain associated with PsA, and increase the proportion of patients whose enthesitis resolved compared with placebo (PBO) in those patients who had an inadequate response or intolerance to ≥1 conventional synthetic disease-modifying antirheumatic drugs (KEEPsAKE 1 and 2) and/or ≤ 2 biological therapies (KEEPsAKE 2). Objectives To investigate whether patients without enthesitis at baseline (BL) (Leeds Enthesitis Index [LEI] = 0 at BL) remained enthesitis-free through week (W) 52, patients with enthesitis at BL (LEI > 0 at BL) had resolution of enthesitis through W52, and if greater pain relief was achieved with RZB 150 mg in patients with enthesitis at BL vs PBO up to W24. Methods The study design and primary results of KEEPsAKE 1 ( NCT03675308 ) and KEEPsAKE 2 ( NCT03671148 ) have been previously reported. 3,4 Briefly, patients were randomized to receive RZB 150 mg or PBO subcutaneously at weeks 0, 4, and 16 during a 24-week, double-blind treatment period; at W28 all patients received open label RZB 150 mg. For this post hoc analysis, the RZB 150 mg and PBO groups were pooled across the 2 studies. Pain reductions (as measured by change from BL in visual analogue scale [VAS] scores) were assessed at each time point through W24 among patients with enthesitis at BL (LEI > 0 at BL) using mixed-effect model repeated measurement analysis. Additional enthesitis analyses were calculated on the data as observed. Results Across the pooled population, over 60% of patients in each treatment group had enthesitis at BL (RZB=444/707 [63%]; PBO=448/700 [64%]). Conversely, 37% (263/707) and 36% (252/700) had no enthesitis (LEI=0) at BL among those randomized to RZB and PBO, respectively. Among enthesitis-free patients at BL (LEI=0 at BL), 84.7% on PBO and 90% on RZB remained free of enthesitis through W24; by W52, approximately 93% of patients in both groups (RZB and PBO to RZB) remained enthesitis free. A numerically higher proportion of patients with enthesitis at BL (LEI > 0 at BL) treated with RZB (52.1%) achieved an enthesitis-free state at W24 vs PBO (41.8%); similar proportions achieved an enthesitis-free state at W36 and W52 during open label treatment (Figure 1). Among patients with enthesitis at BL, a significantly greater improvement in VAS pain scores was observed in patients treated with RZB 150 mg vs PBO, as early as W4 ( P < .01) and increased through W24 (Figure 1; P < .001). Figure 1. Conclusion Long-term maintenance of an enthesitis-free state (LEI = 0) was similar between the RZB 150 mg and PBO groups, with approximately 93% of patients remaining free of enthesitis at W52. For LEI > 0 patients, the RZB 150-mg group had numerically more patients whose enthesitis resolved at W24, and similar proportions were observed at W52 after the open label switch. Patients with enthesitis at BL treated with RZB 150 mg had statistically greater improvements in pain compared with patients taking PBO starting at W4 through to W24. References [1]Orbai A-M, et al. Ann Rheum Dis. 2017;76:673–680. [2]Stavre Z, et al. Arthritis Res Ther . 2022;24(1):24. [3]Kristensen LE, et al. Ann Rheum Dis. 2021;0:1–7. [4]Östör A, et al. Ann Rheum Dis. 2021;0:1–8. Acknowledgements AbbVie Inc. participated in the study design; study research; collection, analysis, and interpretation of data; and writing, reviewing, and approving this abstract for submission. All authors had access to the data; participated in the development, review, and approval of the abstract; and agreed to submit this abstract to EULAR 2022 for consideration as a poster or oral presentation. No honoraria or payments were made for authorship. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. AbbVie funded the research for this study and provided writing support for this abstract. Medical writing assistance, funded by AbbVie, was provided by Kersten Reich, MPH, and Nancy Niguidula, DPH, of JB Ashtin. Disclosure of Interests Marina Magrey Consultant of: MM has received consulting fees from UCB, Novartis, Eli Lilly, Pfizer, and Janssen., Grant/research support from: MM received research grants from Amgen, AbbVie, and UCB Pharma, Manish Jain Consultant of: MJ received consulting fees from Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis., Grant/research support from: MJ received research support from Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis., R Ranza Speakers bureau: RR is a member of speaker bureaus for AbbVie, Janssen, Novartis, and Pfizer, Consultant of: RR is a consultant for AbbVie, Janssen, Novartis, and Pfizer, Jayne Stigler Shareholder of: JS may hold AbbVie stock or stock options., Employee of: JS is a full-time employee of AbbVie., Erin McDearmon-Blondell Shareholder of: EMB may hold AbbVie stock or stock options., Employee of: EMB is a full-time employee of AbbVie., Cuiyong Yue Shareholder of: CY may hold AbbVie stock or stock options., Employee of: CY is a full-time employee of AbbVie., Byron Padilla Shareholder of: BP may hold AbbVie stock or stock options., Employee of: BP is a full-time employee of AbbVie., Christian Kaufmann Shareholder of: CK may hold AbbVie stock or stock options., Employee of: CK is a full-time employee of AbbVie., Dennis McGonagle Speakers bureau: DM is a member of speaker bureaus for AbbVie, Janssen, Novartis, and Pfizer., Grant/research support from: DM received research grants from AbbVie, Janssen, Novartis, and Pfizer, UCB, BMS, Celgene.
