THU0439 EFFICACY AND SAFETY OF ANAKINRA IN THE TREATMENT OF RECURRENT GOUT FLARES: RESULTS FROM THE EXTENSION PHASE OF THE ANAGO STUDY

Background:The anaGO (anakinra ingout) study was a multi-center, randomized, double-blind, double-dummy, phase 2 study investigating the efficacy and safety of anakinra for recurrent gout flares. Results from subsequent flares (extension phase) are presented in relation to the previously reported results from the 1stflare (flare at study enrollment).Objectives:The objective of the extension phase was to evaluate the efficacy, safety and immunogenicity of two anakinra regimens (100 or 200 mg daily s.c. injections for 5 days) compared to triamcinolone (single i.m. injection 40 mg) for subsequent flares after initial study enrollment flare. The primary endpoint of the study was change in patient-assessed flare pain intensity from baseline to 24-72 hours (average of 24, 48 and 72 hours) in the most affected joint measured on a visual analogue scale (0-100 VAS). Secondary endpoints included: patient’s and physician’s assessments of global response, anti-drug antibodies (ADA) and safety.Methods:The study included patients with acute gout (ACR/EULAR 2015 gout classification criteria) unsuitable for anti-inflammatory therapy with NSAIDs and colchicine due to contraindication, intolerance or inefficacy. Patients were eligible for treatment of subsequent flares for up to 2 years. Each patient received the same treatment for all flares, starying with the flare at enrollment.Results:161 patients were treated for 1 flare, 61 patients for 2 flares, 31 patients for 3, and 20 patients for 4 or more flares with 1 patient treated for 9 flares. In total, 300 flares were treated in the full study; anakinra 100 mg and 200 mg, 107 and 106 flares, respectively; and triamcinolone, 87 flares. Both anakinra doses and triamcinolone provided a clinical meaningful reduction in patient-assessed pain intensity in both the 1stand subsequent flares. Mean changes in pain intensity from baseline to 24–72 hours for total anakinra and triamcinolone were: 1stflare -41.2 and -39.4; 2ndflare -33.9 and -31.1; 3rdflare -31.8 and -51.2, respectively. Mean differences in pain reduction between anakinra and triamcinolone treatment groups were (negative value favors anakinra): 1stflare -1.8, 2ndflare -2.8 3rdflare 19.4. The majority of secondary endpoints favored anakinra, including patient’s and physician’s global assessement of response and physician’s assessement of the joint. No unexpected safety findings during subsequent flares were identified. 21 patients (19.6%) developed ADA to anakinra in low titers at some time point; 7 (6.5%) had pre-existing ADA at baseline and 12 (11.2%) developed treatment induced ADA. 2 patients had pre-existing ADA to triamcinolone at baseline. 4 patients on anakinra (3.7%) developed neutralizing antibodies (NAbs). Pre-dose 72 hour anakinra serum concentrations were in similar range for ADA+ and ADA- patients. Presence of ADA was not associated with adverse events or had an impact on pain reduction.Conclusion:The efficacy and safety of anakinra and triamcinolone in subsequent flares were similar to the findings from 1stflare in patients with acute gout. Patient-assessed pain in the 1stand 2ndflare was reduced to similar degrees in all treatment groups, but to a larger extent in the 3rdflare in the small triamcinolone group. Secondary endpoints were in favor of anakinra across flares 1 to 3. The overall incidence of ADA and NAb was low also after repeated anakinra dosing and did not appear to impact exposure, efficacy or safety. In conclusion, anakinra was shown to be an option in the treatment of recurrent gout flares in patients for whom conventional therapy is unsuitable.Disclosure of Interests: :Kenneth Saag Grant/research support from: Horizon, Sobi, Shanton, Grant/research support from: Horizon Pharma, Sobi, Shanton, Consultant of: Horizon and Sobi, Consultant of: Horizon Pharma, Amgen, Radius, LG-Pharma, Takeda, Sobi, Atom, Arthrosi, Puja Khanna Grant/research support from: Dyve, Selecta, Sobi, Consultant of: Sobi, Horizon, Robert Keenan Consultant of: Sobi, Selecta, Horizon, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Erik Sparve Shareholder of: Sobi, Employee of: Sobi, Daniel Lindqvist Employee of: Sobi, Ann-Charlotte Åkerblad Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Alexander So Consultant of: Sobi, Grünenthal, Michael H. Pillinger Grant/research support from: Horizon, Hikma, Consultant of: Sobi, Horizon, Robert Terkeltaub Consultant of: Sobi, Selecta, Horizon, Astra-Zeneca

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THU0409 A RANDOMIZED, PHASE 2 STUDY EVALUATING THE EFFICACY AND SAFETY OF ANAKINRA IN DIFFICULT-TO-TREAT ACUTE GOUTY ARTHRITIS: THE ANAGO STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3766 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 442.1-442 ◽

Cited By ~ 1

Author(s):

K. Saag ◽

A. So ◽

P. Khanna ◽

R. Keenan ◽

S. Ohlman ◽

...

Keyword(s):

Pain Intensity ◽

Primary Endpoint ◽

Clinical Signs ◽

Acute Gout ◽

Phase 2 ◽

Efficacy And Safety ◽

Research Support ◽

Global Response ◽

Treatment Groups ◽

Phase 2 Study

Background:In gout, urate crystals deposited in and around joints trigger episodes of acute arthritis, mediated by the proinflammatory cytokine IL-1β. In uncontrolled studies, the IL-1 receptor antagonist anakinra appears effective in reducing pain and signs of acute flares in patients with difficult-to-treat gout. However, confirmatory, adequately-powered, prospective trials are lacking. The ‘anaGO-study’ (anakinra ingout) was a multi-center, randomized, double-blind, double-dummy, phase 2 study investigating the efficacy and safety of anakinra in acute gout (NCT03002974).Objectives:The primary objective was to evaluate the efficacy of two regimens of anakinra (100 or 200 mg daily s.c. injections for 5 days) compared to triamcinolone (single i.m. injection 40 mg) with respect to patient-assessed pain intensity. The primary endpoint was change in pain intensity from baseline to 24-72 hours (average of 24, 48 and 72 hours) in the most affected joint measured on a visual analogue scale (0-100 VAS). Secondary outcomes included: time to onset of effect, time to response, time to pain resolution, time to rescue medication use, patient’s and physician’s assessments of global response, clinical signs, inflammatory biomarkers and safety.Methods:Patients were recruited who had acute gout based on ACR/EULAR 2015 gout classification criteria, and were unsuitable for anti-inflammatory therapy with NSAIDs and colchicine due to contraindication, intolerance or inefficacy. Patients were randomized to each group in a 1:1:1 ratio and stratified by urate-lowering therapy use (yes/no) and BMI (<30.0 or ≥30.0 kg/m2).Results:165 patients were randomized; 110 to anakinra (56 to 100 mg/day, 54 to 200 mg/day) and 55 to triamcinolone; 108 and 53 were included in the primary analysis, respectively. The median (range) age was 55 (25-83) years, 87% were male, mean disease duration was 8.7 years and mean number of self-reported flares during the past year was 4.5. The pain intensity, from baseline to 24-72 hours, decreased in both treatment groups; mean (95% CI) change was -39.4 (-46.8, -32.0) for triamcinolone and -41.2 (-46.3, -36.2) for anakinra. The 100 mg and 200 mg doses of anakinra were comparably effective in decreasing pain (100 mg/day: -41.8 [-48.9, -34.8] and 200 mg/day: -40.7 [-47.9, -33.4]). Mean (95% CI) difference in pain reduction between anakinra and triamcinolone treatment groups was -1.8 (-10.8, 7.1) (p-value = 0.688 for primary endpoint). The majority of secondary efficacy endpoints were numerically in favor of anakinra, and in most instances also statistically significant, in comparison to triamcinolone, e.g. physician’s assessment of clinical signs at 72 hours and patient’s and physician’s assessment of global response at Day 8. No unexpected safety findings were identified in any of the treatment groups.Conclusion:Anakinra and triamcinolone reduced patient-assessed gout flare pain to similar degrees in patients for whom conventional therapy was ineffective or contraindicated. Both doses of anakinra showed comparable efficacy in pain reduction. The majority of secondary efficacy endpoints favored anakinra. Anakinra was shown to be an additional option for use during acute gout flares.Disclosure of Interests: :Kenneth Saag Grant/research support from: Horizon, Sobi, Shanton, Grant/research support from: Horizon Pharma, Sobi, Shanton, Consultant of: Horizon and Sobi, Consultant of: Horizon Pharma, Amgen, Radius, LG-Pharma, Takeda, Sobi, Atom, Arthrosi, Alexander So Consultant of: Sobi, Grünenthal, Puja Khanna Grant/research support from: Dyve, Selecta, Sobi, Consultant of: Sobi, Horizon, Robert Keenan Consultant of: Sobi, Selecta, Horizon, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Torbjörn Kullenberg Shareholder of: Sobi, Employee of: Former employee of Sobi, Lisa Osterling Koskinen Shareholder of: Sobi, Employee of: Sobi, Michael H. Pillinger Grant/research support from: Horizon, Hikma, Consultant of: Sobi, Horizon, Robert Terkeltaub Consultant of: Sobi, Selecta, Horizon, Astra-Zeneca

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AB0369 EFFICACY AND SAFETY OF RITUXIMAB ORIGINATOR AND BIOSIMILAR IN PRIMARY SJÖGREN’S SYNDROME IN A REAL-LIFE SETTING

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6608 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1485.3-1485

Author(s):

F. Carubbi ◽

A. Alunno ◽

P. Cipriani ◽

V. Pavlych ◽

C. DI Muzio ◽

...

Keyword(s):

Disease Activity ◽

Real Life ◽

Primary Sjögren’S Syndrome ◽

Efficacy And Safety ◽

Research Support ◽

Treatment Groups ◽

Real Life Setting ◽

Patient Reported ◽

Time Point

Background:Over the last 2 decades rituximab (RTX) has been widely used, albeit off-label, in primary Sjögren’s syndrome (pSS). Several studies reported that B-lymphocyte depletion with RTX is effective in this disease not only by reducing disease activity but also by affecting the inflammation and the lymphoid organization that occur in target tissues. With the recent release of several RTX biosimilars (bRTX) on the market, the demonstration of their interchangeability with RTX originator (oRTX) is required.Objectives:To compare efficacy and safety of oRTX and bRTX in pSS patients in a real-life setting.Methods:Clinical records of pSS patients referring to a tertiary rheumatology clinic were retrospectively evaluated. Patients having received at least 2 courses of either oRTX or bRTX (1000 mg IV infusion, repeated after 2 weeks -1 course- and the course repeated after 24 weeks) with complete data at baseline and after 3, 6, 9 and 12 months of treatment were enrolled. Disease activity was assessed with the EULAR SS disease activity index (ESSDAI) and its clinical version without the biological domain (ClinESSDAI). Patient-reported symptoms were assessed with the EULAR SS Patient Reported Index (ESSPRI).Results:Seven patients that received oRTX and 7 patients that received bRTX were enrolled. Baseline clinical features, including ESSDAI and ESSPRI were similar in the 2 treatment groups. Both compounds significantly reduced ESSDAI and ESSPRI as early as 3 months and no difference between the groups was observed at any time point (Figure 1). Of interest, ESSDAI slowly decreased until month 6 when the most pronounced reduction was observed. Conversely, ESSPRI dropped to its lowest values already at month 3. With regard to safety, at 12 months of follow-up no adverse event was observed in any of the treatment groups.Conclusion:At 12 months of follow-up, oRTX and bRTX display similar efficacy and safety profiles. The improvement of patient reported outcomes is faster than the improvement of disease activity with both compounds. Our data support interchangeability of oRTX and bRTX in pSS.References:[1]Carubbi F et al. Arthritis Res Ther. 2013;15(5):R172[2]Carubbi F et al. Lupus. 2014;23(13):1337-49Figure 1 ESSDAI and ESSPRI values at every time point in the 2 treatment groups. Asterisks indicate p values <0.05 compared to the other treatment group at the same time pointDisclosure of Interests:Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Alessia Alunno: None declared, Paola Cipriani Grant/research support from: Actelion, Pfizer, Speakers bureau: Actelion, Pfizer, Viktoriya Pavlych: None declared, claudia di muzio: None declared, Roberto Gerli: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer

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First long-term results on efficacy and safety of long-acting pasireotide in combination with everolimus in patients with advanced carcinoids (NET) of the lung/thymus: Phase II LUNA trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8574 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8574-8574

Author(s):

Eric Baudin ◽

Alfredo Berruti ◽

Mario Giuliano ◽

Wasat Mansoor ◽

Catalin Bobirca ◽

...

Keyword(s):

Phase Ii ◽

Dose Intensity ◽

Extension Phase ◽

Long Term Results ◽

Tolerability Profile ◽

Efficacy And Safety ◽

Open Label ◽

Secondary Endpoints ◽

Core Phase ◽

Long Acting

8574 Background: Everolimus (EVE) improves progression-free survival (PFS) in patients (pts) with progressive non-functioning thoracic and digestive advanced neuroendocrine tumors (NET). The LUNA trial aimed to assess the efficacy and safety of long-acting pasireotide (PAS) and EVE alone or in combination in pts with progressive bronchial or thymic carcinoids. Core phase results for primary endpoint (PFS) and secondary endpoints at 9 and 12 months (mo) were previously published. Cumulative data results at the end of the extension phase are presented here. Methods: LUNA was a prospective, multicenter, randomized, open-label, 3-arm, phase II trial. Adult pts with carcinoids of lung/thymus were randomized (1:1:1) to receive either PAS (60 mg/mo i.m.) or EVE (10 mg/day orally) or PAS + EVE. The key secondary endpoints assessed in this extension phase, including all the patients who were still not progressing at 12 months, were PFS, duration of biochemical response (DBR), and biochemical PFS (BPFS). Results: Of the total 124 pts included in the core phase, 41 pts with a median age of 61 years entered the extension phase including PAS (12), EVE (14) and PAS + EVE (15). Lung was the primary site of cancer in 95.1% and 82.9% had non-functioning tumors. Surgery/local or regional therapy was the preferred prior treatment in 63.4% pts. Disease progression was the primary reason for discontinuation among 3 arms with 65.9% in overall extension phase; no pts in PAS arm discontinued due to adverse events (AEs). Mean relative dose intensity (RDI) was higher for PAS (95.6% alone and 90.4% in combination) when compared to EVE (76.6% alone and 72.4% in combination); 38.1% pts in the EVE arm and 43.9% pts in the combination arm with EVE had RDI <70%. PAS +EVE combination showed clinical benefit in terms of PFS and BPFS compared to PAS and EVE alone as shown in Table. At least one dose reduction of PAS or EVE was reported in >50% pts. Most common AEs of any grade regardless of the study drug in PAS +EVE arm were hyperglycemia (87.8%), diarrhea (80.5%), and weight loss (58.5%), while stomatitis was reported in 34.1%. Twelve deaths were reported during the study and up to 56 days from last study treatment dose. Duration of exposure and efficacy. Conclusions: Mature median PFS and BPFS data suggest a benefit of PAS+EVE combination. The safety and tolerability profile of PAS and EVE alone or in combination were consistent with prior experience of these treatments in the oncology setting, with no new safety signals being reported during the study. Post-hoc prognostic studies are ongoing. Clinical trial information: NCT01563354. [Table: see text]

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Utility of Anakinra in Acute Crystalline Diseases: A Retrospective Study Comparing a University Hospital with a Veterans Affairs Medical Center

The Journal of Rheumatology ◽

10.3899/jrheum.180393 ◽

2018 ◽

Vol 46 (7) ◽

pp. 748-750 ◽

Cited By ~ 8

Author(s):

Julianna Desmarais ◽

Cong-Qiu Chu

Keyword(s):

Retrospective Study ◽

Adverse Effects ◽

Medical Center ◽

Veterans Affairs ◽

Hospitalized Patients ◽

University Hospital ◽

Acute Gout ◽

Efficacy And Safety ◽

Inpatient Management ◽

Gout Flares

Objective.To evaluate the efficacy and safety of anakinra in inpatient management of acute gout and pseudogout.Methods.Hospitalized patients with acute gout (n = 77) or pseudogout (n = 11) or both (n = 3) were analyzed for response to anakinra and adverse effects.Results.Half of all patients had comorbidities limiting the treatment choice. Anakinra was well tolerated, and 92% of gout flares and 79% of pseudogout flares responded to treatment.Conclusion.Anakinra is an effective and safe treatment for acute gout and pseudogout in hospitalized patients, particularly in those with comorbidities.

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Efficacy and Safety of Metamizol vs. Acetylsalicylic Acid in Patients With Moderate Episodic Tension-Type Headache: A Randomized, Double-Blind, Placebo- and Active-Controlled, Multicentre Study

Cephalalgia ◽

10.1046/j.1468-2982.2001.00216.x ◽

2001 ◽

Vol 21 (5) ◽

pp. 604-610 ◽

Cited By ~ 50

Author(s):

P Martínez-Martín ◽

E Raffaelli ◽

F Titus ◽

J Despuig ◽

YD Fragoso ◽

...

Keyword(s):

Pain Relief ◽

Acetylsalicylic Acid ◽

Pain Intensity ◽

Pain Reduction ◽

Tension Type Headache ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Maximum Pain ◽

Type Headache

We assessed the efficacy and safety of oral single doses of 0.5 and 1 g metamizol vs. 1 g acetylsalicylic acid (ASA) in 417 patients with moderate episodic tension-type headache included in a randomized, double-blind, placebo- and active-controlled, parallel, multicentre trial. Eligibility criteria included 18–65 years of age, history of at least two episodes of tension-type headache per month in the 3 months prior to enrolment, and successful previous pain relief with a non-opioid analgesic. Treatment arms were metamizol 0.5 g ( n = 102), metamizol 1 g ( n = 108), ASA 1 g ( n = 102) and placebo ( n = 105). The analgesic efficacy of 0.5 and 1 g metamizol vs. placebo was highly statistically significant (α: 0.025; one-sided) for sum of pain intensity differences, maximum pain intensity difference, number of patients with at least 50% pain reduction, time to 50% pain reduction, maximum pain relief and total pain relief. A trend towards an earlier onset of a more profound pain relief of 0.5 and 1 g metamizol over 1 g ASA was noticed. All medications including placebo were almost equally safe and well tolerated.

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Efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release in Chinese patients with active acromegaly: Results from a phase 3, prospective, randomized, and open-label study (LANTERN)

10.21203/rs.2.21467/v1 ◽

2020 ◽

Author(s):

Zhenmei An ◽

Ting Lei ◽

Lian Duan ◽

Pei Hu ◽

Zhongping Gou ◽

...

Keyword(s):

Chinese Patients ◽

Prolonged Release ◽

Efficacy And Safety ◽

Open Label ◽

Phase 3 ◽

Treatment Groups ◽

Intention To Treat ◽

Secondary Endpoints ◽

Active Acromegaly ◽

Lanreotide Autogel

Abstract Background: Lanreotide autogel is a somatostatin analog (SSA) approved for the treatment of acromegaly in 73 countries worldwide; however, it is not yet approved in China. The aim of this study was to evaluate the efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release (PR) in Chinese patients with active acromegaly. Methods: LANTERN was a Phase 3, randomized, open-label, non-inferiority study. Patients with active acromegaly who had undergone surgery ≥3 months prior, or were unlikely or unable to undergo surgery, were treated with lanreotide autogel 60/90/120 mg (monthly deep subcutaneous injection) or lanreotide 40 mg PR (intramuscular injection every 7, 10, or 14 days) for 32 weeks. Primary endpoint was mean change-from-baseline in age-adjusted insulin-like growth factor-1 (IGF-1) standard deviations scores (SDS) at the end-of-study. Secondary endpoints included: growth hormone (GH) levels ≤2.5 µg/L or ≤1.0 µg/L, ≥20% reduction in tumor volume (TV) and safety. Results: In total, 128 patients were randomized and received study treatment. Lanreotide autogel was non-inferior to lanreotide 40 mg PR: treatment difference (95% CI) for IGF-1 SDS between groups was −0.32 (−0.74, 0.11; per protocol population) and −0.27 (−0.63, 0.09; intention-to-treat [ITT] population), respectively. Reductions in IGF-1 (−6.453 vs −7.003) and GH levels (−9.548 µg/L vs −13.182 µg/L), and the proportion of patients with ≥1 acromegaly symptom (−20.3% vs −32.5%) were observed from baseline to end-of-study in lanreotide autogel and lanreotide 40 mg PR groups, respectively. In the lanreotide autogel group, 45.5% (25/55) patients achieved ≥20% reduction in TV compared with 50.9% (25/53) in lanreotide 40 mg PR group (ITT). Safety profiles were similar in both treatment groups. Conclusions: Lanreotide autogel was non-inferior to lanreotide 40 mg PR in Chinese patients with active acromegaly after 32 weeks of treatment.

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P173 Efficacy and safety of upadacitinib versus placebo and adalimumab in patients with active PsA and inadequate response to non-biologic DMARDs (SELECT-PSA-1): a double-blind, randomised controlled phase III trial

Rheumatology ◽

10.1093/rheumatology/keab247.168 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Iain McInnes ◽

Jaclyn Anderson ◽

Marina Magrey ◽

Joseph F Merola ◽

Yi Liu ◽

...

Keyword(s):

Study Drug ◽

Control Measures ◽

Phase Iii ◽

Musculoskeletal Symptoms ◽

Stock Ownership ◽

Inadequate Response ◽

Efficacy And Safety ◽

Research Support ◽

Double Blind ◽

Secondary Endpoints

Abstract Background/Aims Upadacitinib (UPA) is a JAK inhibitor under evaluation for PsA treatment. We aimed to assess efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients with prior inadequate response (IR) or intolerance to ≥ 1 non-biologic DMARD. This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods Patients with active PsA (≥3 swollen, ≥3 tender joints), active/historical psoriasis, ≤2 non-bDMARDs were randomized 1:1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), ADA 40mg every other week, or PBO. Primary endpoint: proportion of patients achieving ACR20 for UPA vs PBO at Wk12. Secondary endpoints: change in HAQ-DI, FACIT-F, SF-36-PCS (Wk12), sIGA of Psoriasis 0/1, PASI75, change in Self-Assessment of Psoriasis Symptoms (Wk16), change in modified Sharp/van der Heijde Score (mTSS), proportion patients achieving MDA, resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk24), non-inferiority and superiority vs ADA for ACR20, superiority for HAQ-DI, patient assessment of pain NRS (Wk12). Additional secondary endpoints: ACR50/70 at Wk12 and ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) through Wk24 reported for patients receiving ≥1 dose of study drug. Results 1,705 patients were randomised; 1,704 received study drug (mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% on ≥ 1 concomitant non-bDMARD. At Wk12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p < 0.001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p < 0.001 for UPA15/30 vs ADA; superiority, p < 0.001 for UPA30 vs ADA). More patients achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA30 vs ADA for improvement in pain. At Wk24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p < 0.001 for UPA15/30 vs PBO). Rates of TEAEs and serious AEs, including serious infections, were similar in PBO, UPA15, and ADA arms and higher with UPA30. Herpes zoster rates were similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in both the PBO and UPA15 arms; 3 malignancies were reported in both UPA30 and ADA arms. VTE were reported in 1 PBO patient, 1 UPA30 patient and 2 ADA patients. One death occurred in the PBO arm. Conclusion In this non-bDMARD-IR PsA population UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue and inhibited radiographic progression; improvements observed by Wk2. At Wk12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO patients achieved stringent disease control measures (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared to the safety profile observed in RA. Disclosure I. McInnes: Other; I.McI has received research grants and honoraria from Abbvie, BMS, Celgene, Novartis Lilly, Janssen, Pfizer, UCB. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. M. Magrey: Consultancies; M.M. has received consulting fees from Novartis, Eli Lilly, Pfizer, and Janssen. Grants/research support; M.M. has received grants/ research support from Amgen, AbbVie, and UCB Pharma. J.F. Merola: Consultancies; J.F.M. is a consultant for Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma. Y. Liu: None. M. Kishimoto: Consultancies; M.K. has received consulting fees from AbbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma. Honoraria; M.K. has received honoraria/ speakers fees from AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma. S. Jeka: None. C. Pacheco-Tena: None. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. L. Chen: Shareholder/stock ownership; L.C. may be a stock/shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. F. Behrens: Honoraria; F.B. has received honoraria and speakers fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grants/ research support from Pfizer, Janssen, Chugai, Celgene and Roche.

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110. A Phase 3, Multicenter, Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem in Chinese Participants With Complicated Intra-abdominal Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.110 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S67-S68

Author(s):

Yihong Sun ◽

Jia Fan ◽

Gang Chen ◽

Xiaofei Chen ◽

Xiaoling Du ◽

...

Keyword(s):

Clinical Cure ◽

Additional Treatment ◽

Double Blind Study ◽

Efficacy And Safety ◽

Phase 3 ◽

Double Blind ◽

Study Drug Administration ◽

Treatment Groups ◽

Secondary Endpoints ◽

Abdominal Infections

Abstract Background In China, the prevalence of infections due to multidrug-resistant gram-negative bacteria is high and additional treatment options for complicated intra-abdominal infections (cIAI) are needed. This study compared the efficacy and safety of ceftolozane/tazobactam (C/T) + metronidazole (MTZ) versus meropenem (MEM) + placebo (pbo) for the treatment of cIAI in adult Chinese participants. Methods This was a phase 3, double-blind study conducted at 21 centers in China (NCT03830333). Participants aged 18-75 years with cIAI requiring surgical intervention within 24 hours of study drug administration were stratified by site of infection and randomized 1:1 to receive 1.5 g C/T (1 g ceftolozane and 0.5 g tazobactam) + 0.5 g MTZ administered intravenously (IV) every 8 hours (q8h) or 1 g MEM + pbo administered IV q8h for 4-14 days. The primary endpoint was clinical cure at test of cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included rates of clinical cure, per-participant microbiologic response, per-pathogen microbiologic response, and adverse events (AE). Non-inferiority for clinical cure at TOC in the CE population was confirmed if the lower bound of the 2-sided 95% CI for the between-treatment difference in the clinical cure rate was larger than −12.5%. Results A total of 134 participants were randomized to each treatment group. Demographics and baseline characteristics were generally well balanced between treatment groups (Table 1). The median (range) age in the ITT population was 50 (18-75) years and 61% were men. The most frequent sites of infection were the appendix (C/T + MTZ, 50.0%; MEM + pbo, 49.3%) and gallbladder (C/T + MTZ, 27.6%; MEM + pbo, 29.1%). Overall, the most frequently isolated pathogens were Escherichia coli (61.4%) and Klebsiella pneumoniae (17.3%); few anaerobes were isolated (Table 1). C/T + MTZ was non-inferior to MEM + pbo for clinical cure in the CE population (C/T + MTZ, 95.2%; MEM + pbo, 93.1%; difference, 2.1% [95% CI, −4.7% to 8.8%]). Results for key secondary endpoints were comparable between treatment groups (Table 2). Rates of AEs were generally similar between treatment groups (Table 3). Conclusion C/T + MTZ was non-inferior to MEM + pbo in the treatment of adult Chinese participants with cIAI and demonstrated a favorable safety profile. Disclosures Xiaofei Chen, n/a, MSD, China (Employee) Xiaoling Du, n/a, MSD, China (Employee) Ye Wang, n/a, MSD, China (Employee) Hui Wang, n/a, MSD, China (Employee) Fang Sun, n/a, MSD, China (Employee) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)

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1768. Efficacy and Safety of Switching From Boosted-Protease Inhibitors (bPI) Plus Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) Regimens to the Once Daily (QD), Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Virologically Suppressed, HIV-1-Infected Adults: Week 96 Results of the Phase 3, Randomized, Non-Inferiority EMERALD Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.153 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S65-S65 ◽

Cited By ~ 1

Author(s):

Joseph Eron ◽

Chloe Orkin ◽

Douglas Cunningham ◽

Federcio Pulido ◽

Frank Post ◽

...

Keyword(s):

Extension Phase ◽

Virologic Suppression ◽

Efficacy And Safety ◽

Research Support ◽

Open Label ◽

Genetic Barrier ◽

Independent Contractor ◽

Grant Recipient ◽

Hiv 1 ◽

Research Grant

Abstract Background The QD STR D/C/F/TAF 800/150/200/10 mg was noninferior to bPI + F/TDF at 48 weeks in EMERALD. Efficacy and safety of D/C/F/TAF through week 96 are presented. Methods EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter noninferiority trial. Virologically suppressed (VL<50 c/mL for ≥2 months) ART experienced (previous non-DRV VF allowed) HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue bPI + F/TDF over 48 weeks. Patients could then continue on D/C/F/TAF or switch from bPI + F/TDF to D/C/F/TAF at week 52 (Late switch, 44 weeks D/C/F/TAF exposure) in a single-arm extension phase until week 96. The percentage of patients with virologic rebound (confirmed VL ≥50 c/mL) cumulative through week 48 and week 96 were primary and secondary endpoints, respectively. Results Of 1141 randomized and treated patients (58% had received ≥5 previous ARVs including screening ARVs; 15% had previous non-DRV VF), 1,080 continued in the extension phase (N = 728 D/C/F/TAF; N = 352 late switch). Few patients had virologic rebound cumulative through week 96 in the D/C/F/TAF arm (3.1%, 24/763). Virologic rebound occurred in 2.3% (8/352) in the late switch arm over 44 weeks D/C/F/TAF treatment. Many rebounders (14/24 and 2/8) resuppressed by week 96. At week 96 a high percentage of patients in the D/C/F/TAF arm (90.7%, 692/763) were suppressed (VL<50 c/mL). In the late switch arm, 93.8% (330/352) maintained virologic suppression after 44 weeks of treatment. No DRV, primary PI, TFV, or FTC RAMs were seen post baseline. Few serious AEs and AE related discontinuations occurred in either arm (Table 1). Improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and seen in the late switch arm (week 52–96), with a small change in TC/HDL-C ratio (Table 1). Conclusion Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at week 96 with no resistance development, and was well tolerated over 96 weeks with bone, renal, and lipid safety consistent with known TAF and cobicistat profiles. Efficacy and safety results in the late switch arm were consistent with week 48 results in the D/C/F/TAF arm. D/C/F/TAF combines the efficacy and high genetic barrier to resistance of DRV with the safety benefits of TAF, even in patients with a history of non-DRV VF. Disclosures J. Eron Jr., Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen: Consultant, Consulting fee and Research grant. C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. D. Cunningham, Janssen: Investigator, Research grant. Gilead: Investigator, Research grant. F. Pulido, Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support and Speaker honorarium. F. Post, Gilead: Consultant and Grant Investigator, Consulting fee and Grant recipient. Viiv: Grant Investigator, Grant recipient. Janssen: Consultant, Consulting fee. MSD: Consultant, Consulting fee. S. De Wit, Janssen: Investigator, Research grant. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen R&D: Independent Contractor, Consulting fee. E. Van Landuyt, Janssen: Employee and Shareholder, Salary.

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Abstract 474: Efficacy and Safety of LCZ696 Compared with Olmesartan in Japanese Patients with Systolic Hypertension

Hypertension ◽

10.1161/hyp.64.suppl_1.474 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Hiromi Rakugi ◽

Kazuomi Kario ◽

Masako Yamaguchi ◽

Naoko Okino ◽

Hiromi Gotou ◽

...

Keyword(s):

Systolic Hypertension ◽

Age Groups ◽

Japanese Patients ◽

Primary Objective ◽

Efficacy And Safety ◽

Once Daily ◽

Treatment Groups ◽

Neprilysin Inhibitor ◽

Angiotensin Receptor Neprilysin Inhibitor ◽

Secondary Endpoints

Objective: To evaluate the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) vs olmesartan in Japanese patients with systolic hypertension (SH). Methods: Patients aged ≥20 yrs with mean sitting (ms) SBP ≥150-<180 mmHg were randomized to once-daily LCZ696 200 mg or 400 mg (forced-titrated from 1-week LCZ696 200 mg), or olmesartan 20 mg for 8 weeks. The primary objective of this study was to test if LCZ696 200 mg is superior over olmesartan in msSBP reductions from baseline at week 8. Secondary endpoints were reductions in msSBP with LCZ696 400 mg, reductions in msDBP and ms pulse pressure (PP), BP control rate, and safety for all treatment groups at week 8. Efficacy and safety was also assessed by age (<65 and ≥65 years). Results: A total of 1161 patients (LCZ696 200 mg, n=387; LCZ696 400 mg, n=385; olmesartan, n=389) were randomized. Demographic and baseline characteristics were generally comparable across the treatment groups with mean age of 58.7 yrs (<65 yrs, 771 [67.1%]; ≥65 yrs, 382[32.9%]). The msSBP reductions at week 8 with LCZ696 200 mg were statistically significantly superior to olmesartan and significantly greater with LCZ696 400 mg than olmesartan (Table). Reductions in msDBP and msPP were significantly greater and BP control rates were significantly higher with LCZ696 vs olmesartan. Greater BP and PP lowering with LCZ696 vs olmesartan was independent of age. The incidence of AEs was similar across the treatment and age groups. Conclusion: Treatment with LCZ696 is effective and generally well-tolerated in Japanese patients with SH regardless of age and LCZ696 200 mg showed superior BP lowering effect than olmesartan 20 mg.

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