Frontline thrombectomy strategy and outcome in acute basilar artery occlusion

BackgroundNovel thrombectomy strategies emanate expeditiously day-by-day counting on access system, clot retriever device, proximity to and integration with the thrombus, and microcatheter disengagement. Nonetheless, the relationship between native thrombectomy strategies and revascularization success remains to be evaluated in basilar artery occlusion (BAO).PurposeTo compare the safety and efficacy profile of key frontline thrombectomy strategies in BAO.MethodsRetrospective analyses of prospectively maintained stroke registries at two comprehensive stroke centers were performed between January 2015 and December 2019. Patients with BAO selected after MR imaging were categorized into three groups based on the frontline thrombectomy strategy (contact aspiration (CA), stent retriever (SR), or combined (SR+CA)). Patients who experienced failure of clot retrieval followed by an interchanging strategy were categorized as a fourth (switch) group. Clinicoradiological features and procedural variables were compared. The primary outcome measure was the rate of complete revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) grade 2c–3). Favorable outcome was defined as a 90 day modified Rankin Scale score of 0–2.ResultsOf 1823 patients, we included 128 (33 underwent CA, 35 SR, 35 SR +CA, and 25 switch techniques). Complete revascularization was achieved in 83/140 (59%) primarily analyzed patients. SR +CA was associated with higher odds of complete revascularization (adjusted OR 3.04, 95% CI 1.077 to 8.593, p=0.04) which was an independent predictor of favorable outcome (adjusted OR 2.73. 95% CI 1.152 to 6.458, p=0.02). No significant differences were observed for symptomatic intracranial hemorrhage, functional outcome, or mortality rate.ConclusionAmong BAO patients, the combined technique effectively contributed to complete revascularization that showed a 90 day favorable outcome with an equivalent complication rate after thrombectomy.

Tolerability and Safety of Switching from Rituximab to Ocrelizumab: Evaluating Factors Associated with Infusion Related Reactions

Background Ocrelizumab and rituximab are frequently used treatments for multiple sclerosis (MS). Data on switching from rituximab to ocrelizumab is limited. Objectives To assess the frequency, severity, and factors of infusion related reactions (IRRs) in patients with MS who switch from rituximab to ocrelizumab, compared to those who stay on rituximab. Methods Prospective study on MS patients aged 18–65, on rituximab for at least 2 cycles, who either switched to ocrelizumab (switch group) or stayed on rituximab (comparator group) (n = 100 each). Participants were followed for IRRs, safety, and tolerability over 12 months. Results The proportion of IRRs in patients who continue on rituximab (14%) were similar to those who switched to ocrelizumab on Day 1 (14%; p = 1.000) and Week 24 (12%; p = 0.647) but higher than at Day 15 (4%; 0.005). The risk of IRRs for the switch group was associated with the presence of B cells (CD19 and/or CD20 counts ≥1%) increasing by 5.01 (1.49, 16.82) times on Day 1 (p = 0.007). Antidrug antibodies to ocrelizumab were not associated with IRRs. No other safety concerns were identified in switching to ocrelizumab. Conclusion IRRs are similar between both groups, which suggests that it is safe to switch from rituximab to ocrelizumab.

1434. Treatment Patterns, Healthcare Resource Use, and Associated Costs in Females with Uncomplicated Urinary Tract Infection in the United States

Background Urinary tract infections (UTIs) disproportionately affect women and are a substantial burden on healthcare systems. We assessed the effect of antibiotic (AB) switching on UTI recurrence, healthcare resource use (HRU), and related costs among adolescent and adult females in the US with uncomplicated UTIs (uUTIs). Methods This retrospective cohort study used US Optum claims data (United Healthcare, January 1, 2013–December 31, 2018). Eligible patients were females ≥ 12 years of age with an acute uUTI diagnosis at outpatient or emergency department (ED) visit (index date) and an oral AB prescription within ± 5 days of index. Patients with recurrent UTIs (rUTIs), defined as 2 UTI diagnoses (including index) in 6 months or ≥ 3 UTI diagnoses (including index) in 12 months, were included; those with complicated UTI were excluded. Patients were assigned to two groups: AB switch (≥ 2 filled prescriptions of different AB within 28 days post index [uUTI episode]) and no AB switch. Results In 5870 eligible patients (mean age 44.5 years; 76.6% White), ciprofloxacin (CIP; 38.6%), nitrofurantoin (NFT; 31.4%), and trimethoprim-sulfamethoxazole (TMP-SMX; 25.6%) were the most commonly prescribed first-line ABs at index, and 567 (9.7%) patients switched AB. CIP was switched to NFT and TMP-SMX in 2.0% and 1.7% of patients, respectively. NFT was switched to CIP and TMP-SMX in 2.6% and 1.5% of patients, respectively. TMP-SMX was switched to CIP and NFT in 3.0% and 2.4% of patients, respectively. During index visit, the AB switch group had higher mean ambulatory care and pharmacy claims (both p < 0.001), and higher total mean HRU costs (&2186.4) per patient compared with the no switch group (&1508.8; p = 0.011). More patients had rUTI in the AB switch group (18.9%) versus the no switch group (14.2%; p < 0.001), and more had ED visits in the AB switch group than the no switch group (p < 0.0001) (Table 1). During follow-up, the AB switch group had a higher mean number of uUTI episodes per patient (p < 0.001; Table 1), and more patients had UTI-related ED visits (10.8%) compared with the no switch group (7.7%; p = 0.010; Table 2). Table 1. Primary outcomes of uncomplicated UTI outpatients during January 1, 2013–December 31, 2018, stratified by any switch in AB use during index episode Table 2. Primary outcomes of uncomplicated UTI outpatients during January 1, 2013–December 31, 2018, stratified by any switch in AB use during 12-month follow-up Conclusion US females with uUTI who switched AB had more rUTI cases and increased overall costs and HRU compared with those who did not switch AB, suggesting an unmet need for improved prescribing practices. Disclosures Rena Moon, MD, Premier Applied Sciences, Premier Inc. (Employee) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Alex Kartashov, PhD, Premier Applied Sciences, Premier Inc. (Employee) Ning Rosenthal, MD, Premier Applied Sciences, Premier Inc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

195. Intravenous to Oral Antibiotics Versus Intravenous Antibiotics: A Step-Up or a Step-Down for Extended Spectrum Beta-Lactamase Producing Urinary Tract Infections?

Background The treatment of extended-spectrum beta-lactamase (ESBL)-producing urinary tract infections (UTI) may include either intravenous (IV) or oral (PO) antibiotics, according to the Infectious Diseases Society of America guidelines for resistant gram negative infections. The purpose of this study is to evaluate if PO step-down antibiotics, the switch group, compared to continued IV therapy in these UTIs affects clinical outcomes. Methods This multicenter retrospective cohort study was conducted in hospitalized patients with an ESBL-producing UTI between July 2016 and March 2020. The control group received a complete antibiotic course with a carbapenem. The switch group was transitioned to an oral agent within five days from initiation of a carbapenem. The primary endpoint was a composite all-cause clinical failure, which was defined as readmission or hospital mortality within 30 days of hospital discharge or a change in antibiotic during hospital admission. The secondary endpoints included individual components of the primary outcome, readmission indication, inpatient length of stay, direct antibiotic costs, and adverse events. Results The study included 153 patients: 95 and 58 patients in the control and switch groups, respectively. Demographics between the two groups were similar (Table 1). The mean ± SD duration of therapy was 8.7 ± 3.1 and 7.1 ± 3.3 days, respectively. Four oral agents were used for step-down therapy (Figure 1). The primary outcome occurred in 28% in both groups (27 vs 16 patients, p=0.91). The individual components of the primary outcome and readmission indication were also similar: readmission (93% vs 94%, p=0.95), readmission due to a recurrent UTI (33% vs 25%, p=0.73), hospital mortality (7% vs 6%, p=1.0), and change in antibiotic (0% vs 2%, p=0.38). The median (IQR) length of stay and direct antibiotic cost in the control and switch groups were 8 (6) vs 5 (2) days (p< 0.01) and &278 (&244) vs &180 (&104) (p< 0.01), respectively. Adverse events were similar in both groups except for diarrhea (15% vs 2%, p=0.01). Table 1. Baseline Demographics. SD: standard deviation, ICU: intensive care unit, qSOFA: quick Sequential Organ Failure Assessment, ESBL: extended spectrum beta-lactamase, UTI: urinary tract infection Figure 1. Oral Antibiotics. QD: once daily, BID: twice daily, Q2D: every 2 days, Q3D: every 3 days, DS tab: double strength tablet Conclusion There was no difference in clinical failure, readmission rate, mortality rate, or change in antibiotic between the control and switch groups; however, the switch group was associated with reduced hospital length of stay and direct antibiotic cost. Disclosures All Authors: No reported disclosures

Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial

Background Primary analysis at 24 weeks showed that switching to rilpivirine plus darunavir/cobicistat was non-inferior to continuing a standard three-drug antiretroviral regimen in virologically suppressed people with HIV. We present efficacy and safety data from the 48-week analysis. Methods PROBE 2 is a randomized, open-label trial. Adults who were on a three-drug therapy and had had <50 HIV-1 RNA copies/mL for at least 6 months were randomly assigned (1:1) to 25 mg rilpivirine plus 800/150 darunavir/cobicistat once daily (early switch group) or to continue their regimen for 24 weeks before switching (late switch group). In the 48-week analysis, the efficacy endpoint was the proportion of participants with <50 copies/mL of HIV-RNA (US Food and Drug Administration snapshot algorithm). The trial is registered with ClinicalTrials.gov , number NCT04064632. Findings 160 participants were recruited and randomized. At week 48, 70 (87.5%) in the early switch group and 76 (94.8%) in the late switch group maintained HIV-RNA <50 copies/mL. Virological failure (≥50 HIV-RNA copies/mL) was not seen in any patient of the early switch group and in 2 subjects in the late switch group none of which had treatment emergent resistance-associated mutation. Adverse events leading to treatment discontinuation occurred in 7 (8.7%) participants in the early switch group and in none in the late switch group. Interpretation The combination of rilpivirine plus darunavir/cobicistat sustained virological suppression, was associated with a low frequency of virological failure, and had a favorable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and integrase inhibitor-sparing alternative to three-drug regimens.

Clinical effectiveness of diquafosol ophthalmic solution 3% in Korean patients with dry eye disease: a multicenter prospective observational study

AIM: To investigate the effectiveness of diquafosol ophthalmic solution 3% administered in Korean patients with dry eye disease in real-world clinical settings. METHODS: Diquafosol was administered for 8wk to 3 patient groups who received diquafosol as add-on therapy to existing medication (Add group, n=150); received diquafosol only (Monotherapy group, n=196); or discontinued part of their existing medication in favor of diquafosol (Switch group, n=11). Tear break-up time (TBUT), cornea and conjunctival staining based on National Eye Institute/Industry scoring scheme, subjective symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, and meibum quality and expressibility were evaluated at baseline, week 4, and week 8. RESULTS: The mean TBUT increased (from 3.46, 3.92, and 5.84s, respectively, to 5.15, 5.53, and 8.59s, respectively) and corneal staining score decreased (from 2.23, 2.24, and 3.09, respectively, to 0.85, 0.97, and 1.64, respectively) in a time-dependent manner from baseline to week 8 in all three groups. Conjunctival staining score, OSDI questionnaire, and meibum quality and expressibility improved over time from baseline to week 8 in the Add and Monotherapy groups, but differences were not statistically significant in the Switch group. CONCLUSION: Diquafosol improves subjective symptoms and objective signs in patients treated with existing medicines combined with diquafosol and treated solely with diquafosol. Diquafosol can be used as an effective therapeutic agent for dry eye disease or additionally applied in patients who have insufficient response to existing medicines.

Four-Year Teriparatide Followed by Denosumab vs. Continuous Denosumab in Glucocorticoid-Induced Osteoporosis Patients With Prior Bisphosphonate Treatment

ObjectivesIn our previous 24-month study, we observed that teriparatide had some advantages over denosumab for bone mineral density (BMD) in glucocorticoid-induced osteoporosis (GIO) patients with prior bisphosphonate treatment. We conducted this extension study to investigate whether the advantage of teriparatide obtained in the first 2 years would be maintained after the switch to denosumab.Materials and MethodsWe switched patients who had completed 24-month daily teriparatide treatment to denosumab (switch group, n=18) and compared their BMD every 6 months up to 48 months with the group who continued to receive denosumab (denosumab group, n=16).ResultsAt 48 months, the lumbar spine BMD was significantly increased from baseline in both groups (denosumab: 10.4 ± 8.7%, p&lt;0.001; switch: 14.2 ± 6.8%, p&lt;0.001). However, a significant increase in femoral neck BMD from baseline occurred only in the switch group (11.2 ± 14.6%, p&lt;0.05); denosumab (4.1 ± 10.8%). The total hip BMD increased significantly from baseline in both groups (denosumab: 4.60 ± 7.4%, p&lt;0.05; switch: 7.2 ± 6.9%, p&lt;0.01). Femoral neck BMD was significantly increased in the switch versus the denosumab group (p&lt;0.05).ConclusionIn GIO patients with prior bisphosphonate treatment, the advantage of teriparatide may be maintained after the treatment period. A continuous increase in BMD can be expected with teriparatide followed by denosumab.

A Prospective Observational Study on the Efficacy and Safety of Infliximab-Biosimilar (CT-P13) in Patients With Takayasu Arteritis (TAKASIM)

Objectives: Infliximab (IFX) is widely used in patients with refractory Takayasu arteritis (TAK). Recently, the IFX-biosimilar CT-P13 has been introduced for the treatment of inflammatory diseases. The aim of this study was to assess the efficacy and safety of CT-P13 in patients with refractory TAK.Methods: In this prospective, open-label, single-center trial, TAK patients either already on treatment with IFX-originator (switch group) or never treated with IFX (naïve group) received CT-P13 for 52 weeks. The primary outcomes of the study were: (i) number of patients with active disease at month 6; (ii) incidence of treatment-emergent adverse events at month 12. Disease activity was assessed at month 6 and month 12 by clinical evaluation (ITAS-2020, ITAS-ESR, and ITAS-CRP scores) and imaging assessment [magnetic resonance angiography (MRA) and (18F)-FDG-PET].Results: 23 patients were recruited (21 switch, 2 naïve). At baseline, 7 patients (32%) were classified as active. At month 6, one patient voluntarily dropped out and 7 patients were still active (30%), including one patient started on a different bDMARD at month 2 due to poor disease control. Mean daily dose of prednisone equivalent was significantly lower than baseline (4.2 ± 1.9 mg vs. 4.8 ± 2.1 mg, p = 0.009). At month 12, another patient was excluded because of pregnancy desire. Five patients were classified as active (24%), including two patients started on a different bDMARD at month 2 and month 6. Mean daily dose of prednisone equivalent was significantly lower than baseline (3.3 ± 2.6, p = 0.034). No patient experienced side effects during CT-P13 infusion. Overall, one patient experienced grade 1 adverse event and 9 patients experienced grade 2 adverse events. In no case hospitalization was required. CT-P13 retention rate was 90.9% at month 6 and 90.4% at month 12.Conclusion: In this study, the use of IFX-biosimilar CT-P13 in patients with refractory TAK showed satisfying efficacy and safety profile.

HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA

Background Certain risk alleles associated with autoantibody-positive rheumatoid arthritis (RA) have been linked to poorer prognoses. In patients with autoantibody-positive RA, abatacept shows differential efficacy to tumor necrosis factor inhibitors. Our aim was to investigate the relationship between clinical response to abatacept and to adalimumab and presence of risk alleles encoding human leukocyte antigen (HLA)-DRB1 shared epitope (SE) in RA. Methods In this head-to-head study, biologic-naïve adults with early (≤ 12 months), moderate-to-severe RA and inadequate response to methotrexate (MTX-IR), autoantibody-positive for both anti-cyclic citrullinated peptide 2 and rheumatoid factor, were randomized 1:1 to receive subcutaneous abatacept 125 mg weekly or subcutaneous adalimumab 40 mg every 2 weeks for 24 weeks with stable, weekly oral MTX. An open-label period to 48 weeks followed, during which adalimumab-treated patients were switched to abatacept. Patients were genotyped for HLA-DRB1 alleles and classified as SE-positive (≥ 1 SE allele) or SE-negative (no SE alleles). Efficacy was assessed at weeks 24 and 48. Results Forty patients each received abatacept (9 SE-negative, 30 SE-positive, one unknown) or adalimumab (9 SE-negative, 31 SE-positive). Mean age and disease duration were 46.0 years and 5.5 months, respectively. At week 24, a greater percentage of abatacept patients achieved 50% improvement in ACR criteria (ACR50) compared with adalimumab patients (73% vs 45%, respectively) and estimate of difference (95% confidence interval [CI]), 28 (5, 48). In SE-positive patients, ACR50 estimate of difference (95% CI) was 32 (7, 55). During the open-label period, responses were sustained in the abatacept non-switch group and showed trends toward further improvement in the adalimumab-to-abatacept switch group at week 48, in both the overall and the SE-positive subpopulation. No new safety signals were identified. Conclusions In MTX-IR patients with early, autoantibody-positive RA, abatacept resulted in numerically higher efficacy responses versus adalimumab after 24 weeks, with more pronounced treatment differences in SE-positive patients. After 48 weeks, responses were sustained in patients who continued abatacept while those who switched to abatacept showed further clinical improvement, overall, and in SE-positive patients. This supports co-stimulation blockade as an effective treatment strategy for patients with early, autoantibody-positive RA, particularly among SE-positive patients. Trial registration NIH US National Library of Medicine, NCT02557100. Registered on September 23, 2015.

Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.