scholarly journals Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

2016 ◽  
Vol 43 (12) ◽  
pp. 2120-2130 ◽  
Author(s):  
Jonathan Kay ◽  
Roy Fleischmann ◽  
Edward Keystone ◽  
Elizabeth C. Hsia ◽  
Benjamin Hsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Opportunistic Infections ◽  
Safety Data ◽  
Phase 3 ◽  
Tnf Antagonists ◽  
Link Type ◽  
Serious Infections ◽  
Necrosis Factor

Objective.Assess 5-year golimumab (GOL) safety in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).Methods.Subcutaneous (SC) GOL (50 mg or 100 mg every 4 weeks) was evaluated in phase 3 trials of patients with active RA, PsA, and AS. Safety data through Year 5 were pooled across 3 RA trials [1 each evaluating methotrexate (MTX)-naive, MTX-experienced, and antitumor necrosis factor (TNF)-experienced patients], 1 PsA trial, and 1 AS trial. Data summarized was derived from both placebo-controlled (through weeks 24–52) and uncontrolled study periods. For adverse events (AE) of special interest [serious infections (SI), opportunistic infections (OI), deaths, malignancies, demyelination, tuberculosis (TB)], incidence per 100 patient-years (pt-yrs) was determined.Results.Across all trials, 639 patients received placebo and 2228 received SC GOL 50 mg only (n = 671), 50 mg and 100 mg (n = 765), or 100 mg only (n = 792). Safety followup extended for averages of 28.5 and 203.2 weeks for placebo and GOL, respectively. Respective placebo and GOL AE incidence/100 pt-yrs (95% CI) through Year 5 were 4.86 (2.83–7.78) and 3.29 (2.92–3.69) for SI, 0.00 (0.00–0.86) and 0.23 (0.14–0.35) for TB, 0.00 (0.00–0.86) and 0.22 (0.13–0.34) for OI, 0.00 (0.00–0.86) and 0.10 (0.05–0.20) for lymphoma, 0.00 (0.00–0.86) and 0.08 (0.03–0.17) for demyelination, and 0.29 (0.01–1.59) and 0.41 (0.29–0.57) for death. TB, OI, lymphoma, and demyelination incidence appeared to be higher among patients receiving GOL 100 mg only.Conclusion.SC GOL safety through Year 5 remained consistent with previously reported Year 3 findings and with other TNF antagonists. Numerically higher incidences of TB, OI, lymphoma, and demyelination were observed with 100 mg versus 50 mg. Clinicaltrials.gov identifiers: NCT00264537 (GO-BEFORE), NCT00264550 (GO-FORWARD), NCT00299546 (GO-AFTER), NCT00265096 (GO-REVEAL), and NCT00265083 (GO-RAISE).

THU0373 SECUKINUMAB DOSE ESCALATION ON ACR RESPONSES IN ANTI-TUMOUR NECROSIS FACTOR NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS: 2-YEAR DATA FROM THE PHASE 3 FUTURE 4 AND FUTURE 5 STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 418.1-419
Author(s):  
P. Emery ◽  
M. Ǿstergaard ◽  
L. C. Coates ◽  
A. Deodhar ◽  
E. Quebe-Fehling ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Tumour Necrosis Factor ◽  
Dose Escalation ◽  
Tumour Necrosis ◽  
Research Support ◽  
Phase 3 ◽  
Post Dose ◽  
Link Type ◽  
Necrosis Factor

Background:Secukinumab (SEC) 150 and 300 mg doses are approved for the treatment of psoriatic arthritis (PsA). SEC 300 mg is the recommended dose for patients (pts) with concomitant moderate-to-severe plaque psoriasis or who are anti-tumour necrosis factor (TNF) inadequate responders. An increase from 150 mg to 300 mg has been reported to be beneficial in some patients with a suboptimal response to SEC 150 mg.1Here, we present a post hoc analysis in anti-TNF naïve pts who escalated from SEC 150 to 300 mg dose in two Phase 3 studies, FUTURE 4 (NCT02294227) and FUTURE 5 (NCT02404350).Objectives:To evaluate the clinical efficacy on joints following dose escalation from SEC 150 to 300 mg on ACR responses in anti-TNF naïve pts with PsA.Methods:Study design, patient inclusion and exclusion criteria of the FUTURE 4 and FUTURE 5 studies have been reported previously.1–3In FUTURE 4, 341 pts were randomised in a 1:1:1 ratio to SEC 150 mg with loading dose (LD), SEC 150 mg without LD, or placebo. In FUTURE 5, 996 pts were randomised in a 2:2:2:3 ratio to SEC 300 mg with LD, SEC 150 mg with LD, SEC 150 mg without LD or placebo. Following a protocol amendment, pts were allowed to escalate from 150 mg to the 300 mg dose, in the event of suboptimal response based on investigator’s judgment, starting at Week 36 in FUTURE 4 and at Week 52 in FUTURE 5. ACR responses in anti-TNF naïve pts were evaluated pre- and up to 32 and 40 weeks post-escalation, in FUTURE 4 and FUTURE 5, respectively: pts were grouped into four ranges based on their response: no (< 20); low (≥ 20 to < 50); moderate (≥ 50 to < 70); high (≥ 70) ACR responses. Data presented are as observed in the Sankey-style overlay plot.Results:Dose escalation from SEC 150 to 300 mg occurred in 136 pts in FUTURE 4 and in 236 pts in FUTURE 5. The proportion of ACR responders increased and the proportion of non-responders decreased in anti-TNF naïve pts who escalated from SEC 150 to 300 mg in the two studies. The proportion of anti-TNF naïve pts with a response ≥ACR50 increased from 20% to 41% in FUTURE 4 and 28% to 46% in FUTURE 5, post dose escalation. The ACR responses in anti-TNF naïve pts up to 40 weeks after escalation from SEC 150 to 300 mg are presented in the Sankey-style overlay (Figure).Figure.ACR Response bar chart with Sankey-style overlays up to 40 weeks, after dose escalation from SEC 150 mg to 300 mg, in anti-TNF naïve pts in FUTURE 4 and 5Conclusion:The proportion of ACR responders increased within 12-16 weeks and was sustained up to 40 weeks following dose escalation in anti-TNF naïve pts with PsA. These results suggest that dose escalation from SEC 150 to 300 mg may be beneficial in anti-TNF naïve pts with a suboptimal response on SEC 150 mg.References:[1]Kivitz AJ, et al. Rheumatol Ther. 2019;6(3):393–407;[2]Mease PJ, et al. Ann Rheum Dis. 2018;77:890–7;[3]Mease, P.J., et al. ACR Open Rheumatology. 2019 [ePub ahead of print] doi:10.1002/acr2.11097.Disclosure of Interests:Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Laura C Coates: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Erhard Quebe-Fehling Shareholder of: Novartis, Employee of: Novartis, Pascale Pellet Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis, Employee of: Novartis, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB

scholarly journals P191 Secukinumab demonstrates a consistent safety profile in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis over long term: updated pooled safety analyses

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Iain B McInnes ◽  
Xenofon Baraliakos ◽  
Atul Deodhar ◽  
Alice B Gottlieb ◽  
Mark Lebwohl ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Safety Data ◽  
Cardiac Events ◽  
Research Support ◽  
Phase 3 ◽  
Research Grants ◽  
Adverse Cardiac Events ◽  
Post Marketing

Abstract Background/Aims  Pooled safety data have been reported with secukinumab in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS) and psoriasis (PsO). Here we report longterm safety data for secukinumab in patients with PsA, AS or PsO up to 5 years. Methods  The integrated clinical trial safety dataset included data pooled from 28 randomised controlled clinical trials of secukinumab 300, 150 or 75 mg in PsO (11 Phase 3 and 8 Phase 4 trials), PsA (5 Phase 3 trials) and AS (4 Phase 3 trials), along with post-marketing safety surveillance data starting 26 December 2014, with a cut-off date of 25 December 2018. Adverse events were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥1 dose of secukinumab. Results  A total of 12,637 patients (8,819, 2,678 and 1,140 patients with PsO, PsA and AS, with an exposure of 15,063.1, 5,984.6 and 3,527.2 patient-years, respectively) were included. The most frequent adverse event was upper respiratory tract infection and the EAIR per 100 patient-years for inflammatory bowel disease (IBD), malignancies and major adverse cardiac events (MACE) remained low. The EAIR per 100 patient-years for adverse events of special interest are reported in Table 1. The cumulative post-marketing exposure to secukinumab was estimated to be ∼285,811 patient-years across the approved indications. Post-marketing safety data showed cumulative reporting rates of 1.4, 0.3, 0.2 and 0.2 patienttreatment years for serious infections, malignancy, total IBD and MACE, respectively. Conclusion  Secukinumab was well tolerated in this long-term analysis of patients with PsO, PsA and AS across clinical trials and post-marketing surveillance, with a safety profile consistent with previous reports (Deodhar, 2019). P191 Table 1:Selected adverse events of interest with secukinumab across pooled clinical trialsVariablePsOPsAASSEC N = 8,819SEC N = 2,678SEC N = 1,140Exposure (days),mean (SD)623.9 (567.7)816.2 (580.7)1130.1 (583.0)Death, n (%)14 (0.2)11 (0.4)9 (0.8)Selected adverse events of interest, EAIR (95% CI)Serious infectionsa1.4 (1.2-1.6)1.8 (1.5-2.2)1.2 (0.9-1.6)Candida infectionsb2.9 (2.7-3.2)1.5 (1.2-1.9)0.7 (0.5-1.1)IBDc0.01 (0.0-0.05)0.03 (0.0-0.1)0.03 (0.0-0.2)Crohns diseasec0.1 (0.05-0.2)0.1 (0.04-0.2)0.4 (0.24-0.7)Ulcerative colitisc0.1 (0.08-0.2)0.1 (0.04-0.2)0.2 (0.1-0.5)MACEd0.4 (0.3-0.5)0.4 (0.3-0.6)0.7 (0.4-1.0)Uveitisc0.01 (0.0-0.05)0.1 (0.04-0.2)1.2 (0.9-1.7)Malignancye0.9 (0.7-1.0)1.0 (0.77-1.3)0.5 (0.3-0.8)aRates for system organ class;bRates for high level term;cRates for preferred term (PT; IBD for unspecified IBD);dRates for Novartis MedDRA Query term;eRates for standardised MedDRA Query term - ‘malignancies and unspecified tumour’. AS, ankylosing spondylitis; CI, confidence interval; EAIR, exposure-adjusted incidence rate per 100 patient-years; IBD, inflammatory bowel disease; MACE, major adverse cardiac events; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients in the analysis; PsA, psoriatic arthritis; PsO, psoriasis; PT, preferred term; SD, standard deviation; SEC, secukinumab. Disclosure  I. McInnes: Other; I.M. has received research grants, consultation fees or speaker honoraria from AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. X. Baraliakos: Consultancies; X.B. is a consultant for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. Member of speakers’ bureau; X.B. is a member of the speakers' bureau for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. Grants/research support; X.B. has received grant/research support from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. A. Deodhar: Other; A.D. has received honoraria for consulting or speaking for, or has received research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Eli Lilly, GlaxoSmithKline (GSK), Janssen, Novartis, Pfizer and UCB. A. Gottlieb: Other; A.G. has received research grants, consultation fees or speaker honoraria for lectures from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB. M. Lebwohl: Consultancies; M.L. is a consultant for Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Foundation for Research and Education in Dermatology, Inozyme Pharma, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Theravance and Verrica. Grants/research support; M.B. receives receives research funds from AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development, LLC, Kadmon Corp., LLC, LEO Pharma, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, Inc. and ViDac. S. Schreiber: Consultancies; S.S. has received consultation fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Provention Bio, Protagonist, and Dr Falk Pharma. K. Marfo: Other; K.M. is an employee of Novartis with Novartis stock. W. Bao: Other; W.B. is an employee of Novartis with Novartis stock. H. Richards: Other; H.B.R. is an employee of Novartis with Novartis stock. L. Pricop: Other; L.P. is an employee of Novartis with Novartis stock. A. Shete: Other; A.S. is an employee of Novartis with Novartis stock. J. Safi: Other; J.S. is an employee of Novartis with Novartis stock. P. Mease: Consultancies; P.M. is a consultant for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. Member of speakers’ bureau; P.M. is a member of the speakers' bureau for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. Grants/research support; P.M. has received grant/research support from AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB.

scholarly journals Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study

2021 ◽  
pp. annrheumdis-2021-221007
Author(s):  
Ingrid Egeland Christensen ◽  
Siri Lillegraven ◽  
Pawel Mielnik ◽  
Gunnstein Bakland ◽  
Liz Loli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Cox Regression ◽  
Disease Status ◽  
Incidence Rates ◽  
Serious Infections ◽  
Factor Inhibitor ◽  
Necrosis Factor

ObjectivesTo estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA.MethodsWe included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models.ResultsA total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status.ConclusionsCompared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.

scholarly journals Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Fabrizio Cantini ◽  
Carlotta Nannini ◽  
Laura Niccoli ◽  
Linda Petrone ◽  
Giuseppe Ippolito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Underdeveloped Countries ◽  
Increased Risk ◽  
Tuberculosis Reactivation ◽  
Necrosis Factor

Tuberculosis (TB) still represents an important issue for public health in underdeveloped countries, but the use of antitumor necrosis factor agents (anti-TNF) for the treatment of inflammatory rheumatic disorders has reopened the problem also in countries with low TB incidence, due to the increased risk of TB reactivation in subjects with latent tuberculosis infection (LTBI). Over the last 5 years, several non-anti-TNF-targeted biologics have been licensed for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. We reviewed the epidemiology of TB, the role of different cytokines and of the immune system cells involved in the immune response against TB infection, the methods to detect LTBI, and the risk of TB reactivation in patients exposed to non-anti-TNF-targeted biologics. Given the limited role exerted by the cytokines different from TNF, as expected, data from controlled trials, national registries of biologics, and postmarketing surveillance show that the risk of TB reactivation in patients receiving non-anti-TNF-targeted biologics is negligible, hence raising the question whether the screening procedures for LTBI would be necessary.

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