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

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 442.1-442 ◽  
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

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

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 456.1-457
Author(s):  
K. Saag ◽  
P. Khanna ◽  
R. Keenan ◽  
S. Ohlman ◽  
E. Sparve ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Pain Reduction ◽  
Extension Phase ◽  
Acute Gout ◽  
Efficacy And Safety ◽  
Research Support ◽  
Treatment Groups ◽  
Study Enrollment ◽  
Secondary Endpoints ◽  
Gout Flares

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

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

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

scholarly journals POS0198 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 314.2-315
Author(s):  
P. J. Mease ◽  
A. Deodhar ◽  
D. Van der Heijde ◽  
F. Behrens ◽  
A. Kivitz ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Tyrosine Kinase ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Research Support ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Phase 2 Trial ◽  
Tyrosine Kinase 2 ◽  
Sf 36

Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signaling by key cytokines involved in psoriatic arthritis (PsA) and plaque psoriasis (PsO) pathogenesis. Deucravacitinib is a novel oral agent that selectively inhibits TYK2 via an allosteric mechanism by binding to the nonconserved regulatory domain of the kinase. A previous Phase 2 trial in PsO had demonstrated that deucravacitinib was efficacious and well tolerated, with no laboratory abnormalities observed.Objectives:To evaluate the efficacy and safety of deucravacitinib in active PsA.Methods:This is an ongoing, 1-year, randomized, double-blind, placebo (PBO)-controlled (initial 16 weeks), multiregional, Phase 2 trial (NCT03881059). Eligible patients had a PsA diagnosis for ≥6 months, met CASPAR criteria, and had active disease with ≥3 tender and ≥3 swollen joints, C-reactive protein ≥3 mg/L (ULN, 5 mg/L), and ≥1 psoriatic lesion (≥2 cm). Patients had failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, conventional synthetic disease-modifying antirheumatic drug (csDMARD), and/or 1 TNF inhibitor (TNFi; ≤30%). Patients were randomized 1:1:1 to deucravacitinib 6 mg once daily (QD) or 12 mg QD, or PBO. The primary endpoint was achievement of ACR 20 response at Week 16. Additional endpoints included the proportion of patients achieving ACR 50/70 response, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (≥0.35 improvement from baseline), enthesitis resolution (Leeds Index score of 0), minimal disease activity, change from baseline in SF-36 physical component score (SF-36 PCS) and mental component score (SF-36 MCS), Psoriasis Area and Severity Index (PASI) 75 response, adverse events (AEs), and laboratory parameters.Results:Of 203 patients randomized, 180 (89%) completed 16 weeks of treatment (deucravacitinib 6 mg QD, 63/70 [90%]; deucravacitinib 12 mg QD, 59/67 [88%]; PBO, 58/66 [88%]). Demographic and baseline disease characteristics were similar across groups. Mean age was 49.8 years, 51% of patients were female, median PsA duration was 4.5 years, 66% of patients used csDMARDs at baseline and throughout the study, and 15% had used a TNFi. This study met its primary endpoint, with deucravacitinib 6 mg and 12 mg QD demonstrating significantly higher ACR 20 responses versus PBO at Week 16 (Figure 1). Additional endpoints were also met with deucravacitinib versus PBO (Figure 1). Adjusted mean changes from baseline in SF-36 PCS and SF-36 MCS at Week 16, respectively, were significantly higher in the deucravacitinib 6 mg QD group (5.6 vs 2.3, P=0.0062; 3.6 vs 0.7, P=0.0211) and 12 mg QD group (5.8 vs 2.3, P=0.0042; 3.5 vs 0.7, P=0.0263) compared with PBO. PASI 75 responses were also significantly higher in the deucravacitinib groups (P≤0.0136 vs PBO). The most common AEs in the deucravacitinib 6 mg/12 mg/PBO groups, respectively, during the 16-week treatment period were nasopharyngitis (5.7%/17.9%/7.6%), sinusitis (0%/7.5%/0%), headache (7.1%/1.5%/4.5%), and rash (4.3%/6.0%/0%). No serious AEs, herpes zoster infections, opportunistic infections, or thrombotic events were reported in deucravacitinib-treated patients during this period. Additionally, no significant changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, and hemoglobin) or serum lipids were observed with deucravacitinib treatment.Conclusion:Deucravacitinib was efficacious versus PBO over 16 weeks in patients with active PsA. Treatment was generally well tolerated and the safety and laboratory parameter profile of deucravacitinib was consistent with that observed in an earlier Phase 2 PsO trial.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Frank Behrens Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb, UCB Pharma, Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Roche, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis, Paid Consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc., Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie, Jonghyeon Kim Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shalabh Singhal Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

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