Abstract BACKGROUND Musculoskeletal (MSK) disease is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD); however, the full spectrum of MSK manifestations remains poorly characterized. The published literature is predominately focused on peripheral and axial inflammatory spondyloarthritis (SpA). However, the prevalence of more common, non-inflammatory MSK conditions, such as osteoarthritis (OA) and fibromyalgia (FM), has not been formally reported. In the general population, the prevalence of OA and FM are 10-14% and 2-3%, respectively. OBJECTIVE To evaluate the prevalence of OA and FM in the published literature in IBD. METHODS A systematic literature review of articles assessing the prevalence of MSK disease in IBD was performed using multiple databases through September 2021. References of included articles were searched for additional pertinent studies. RESULTS 773 abstracts were screened and 94 studies included. Studies were heterogeneous precluding meta-analysis. Regarding study design, 36% were retrospective, 51% cross-sectional and 13% longitudinal. Median age at the time of the study was 41 years (range 29-51) and 49% (range 31%-100%) were male. The median number of IBD patients in each study was 243 (range 44-56,097). The prevalence of SpA (range) in the reviewed studies was: ankylosing spondylitis (AS) 3.5% (1%-27%), axial SpA 9.2% (1%-46%), and peripheral SpA 15.6% (1%-49%). Only 20/94 studies (21%) stated the term OA in any part of the paper. Of these, 20% excluded OA, 15% used the term OA but did not specifically exclude or identify patients with OA in the results, 5% reported that OA data was unavailable and 60% described the prevalence of OA in the results. In the studies that described OA in the results, median prevalence of OA was 12% (range 0.4%-23.4%). Only 7/94 studies (8%) described FM in any part of the paper, and all described the prevalence of FM in the results with a median prevalence of 2.2% (range 0.8%-12%). CONCLUSION While OA and FM are common conditions in the general population, most studies did not formally evaluate for these conditions in patients with IBD. When assessed, the median prevalence of OA was consistent with the general population, and additionally higher than the prevalence of AS and axial SpA in patients with IBD. The prevalence of FM was consistent with the general population. Although both rheumatologists and gastroenterologists need to recognize the importance of SpA, it is as important to understand that the most common MSK disease in IBD may be non-inflammatory. This distinction is critical, as treatment of IBD patients incorrectly diagnosed with inflammatory SpA may subject patients unnecessarily to medication adverse events, while undertreatment of patients with unrecognized SpA may lead to preventable disease morbidity.
The aim of the study is to examine the frequency and costs associated with above-label dosing of biologics in patients with psoriatic arthritis (PsA). MarketScan identified adults with ≥1 International Classification of Diseases, Clinical Modification diagnosis for PsA and ≥1 pharmacy claim for biologics of interest between January 1, 2011 and December 31, 2013. The first biologic claim was the index date with a 1-year follow-up period and three additional months to confirm continuous biologic use. Exclusion criteria included switching to a different biologic or diagnosis with another autoimmune disease. During the follow-up period, duration was stratified into three groups: <30, 30–179, and ≥180 days of above-label dosing (>10% of the labeled dose). One-tailed t test was conducted to examine the impact of above-label duration on healthcare costs. We identified 4245 PsA patients receiving etanercept (n = 2342), adalimumab (n = 1788), and golimumab (n = 115). Above-label dosing of <30 days (85% adalimumab, 90.4% etanercept, and 95.7% golimumab) and ≥180 days (9.6% adalimumab, 4.1% etanercept, and 2.6% golimumab) was observed. All-cause total healthcare costs for <30 days of above-label use (etanercept $30,625, adalimumab $31,620, and golimumab $37,224), 30–179 days (etanercept $35,602, adalimumab $38,915, and golimumab $64,349), and ≥180 days (etanercept $55,349, adalimumab $54,176, and golimumab $47,993) were reported. Longer above-label duration (30–179 versus <30 days, ≥180 versus 30–179 and ≥180 days) with etanercept or adalimumab was significantly associated with higher mean increased total all-cause healthcare, PsA-specific healthcare, and biologic costs (p < 0.05). Above-label use of anti-TNF biologics does occur and is associated with significantly increased healthcare costs.
The objective of this study is to report long-term, end-of-study-program safety outcomes, relating to major adverse cardiovascular events (MACE), in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA) who received ≥1 dose of Ixekizumab (IXE) over 5 years (PsO) or 3 years (PsA, axSpA).
Methods
The incidence of MACE was assessed across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA) examining long-term safety of IXE. MACE rates were analyzed for pooled studies by years of therapy, through March 2022. Exposure-adjusted incidence rates (IRs) per 100 patient-years, at successive year intervals are reported.
Results
The incidence of MACE was low among patients with PsO (IR=0.5), PsA (IR=0.5), and axSpA (IR=0.3). In the PsO cohort, of the 103 reported MACE cases, 20 were fatal (19.4%), 57 recovered (55.3%), and 17 recovered with sequelae (16.5%). Of the 12 reported MACE cases in the PsA cohort, 2 were fatal (16.7%), 9 recovered (75.0%), and 1 recovered with sequelae (8.3%). All 6 MACE cases reported in the axSpA cohort recovered (100.0%). IRs were low and stable over the treatment periods. The most common types of MACE reported in the PsO, PsA and axSpA cohorts were non-fatal myocardial infarction (PsO: IR= 0.3; PsA: IR=0.3; axSpA: IR=0.3), nonfatal stroke (PsO: IR=0.1; PsA: IR=0.2) and vascular death (PsO: IR=0.1; PsA: IR=0.1). All MACE cases were confirmed by adjudication.
Conclusion
The incidence of MACE was low and stable over the IXE treatment periods examined.
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Disclosure of Interests
Mark Lebwohl Consultant of: Arcutis, Boehringer Ingelheim, Bristol Myers. Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma, Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte. Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy's Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Corrona), Grant/research support from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara. Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Sergio Schwartzman Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, Novartis, UCB, Consultant of: AbbVie, Janssen, Eli Lilly and Company, Pfizer, Novartis, UCB, Myriad, Regeneron, Sanofi, Stelexis, Jubilant, Teijin, National Psoriasis Foundation Medical Boar, Grant/research support from: Lilly, Carlo Salvarani Consultant of: AbbVie, Eli Lilly and Company, and Roche, Grant/research support from: Roche, Meghan Feely Shareholder of: Eli Lilly and Company, Speakers bureau: Mount Sinai, Consultant of: Mount Sinai, Hospital, NY, Eli Lilly and Company, Aerolase, Castle Biosciences, Galderma Aesthetics, Revian, Sonoma Pharmaceuticals, Suneva Medical, and Sun Pharmaceutical Industries, AAD Investment Committee, AAD Media Expert Team, AEI Leadership Network, Leonine Forum, WDS Committees: Practice Advisory, Finance and Investment, Fundraising and Philanthropic Activities, Prevention Medical Review Board, ASDS Social Media Ambassador, Grant/research support from: Eli Lilly and Company, Mount Sinai, MC Medical Group, The Dermatology and Laser Group, Windsor Dermatology, Employee of: Eli Lilly and Company, Danting Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Proton Rahman Consultant of: AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis, Kim Papp Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merck, Novartis, Pfizer, Sanofi, Consultant of: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv. Therapeutics, Xencor, Grant/research support from: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv. Therapeutics, Xencor, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Regeneron, Sun Pharma, and UCB Pharma, Alice B Gottlieb Shareholder of: Xbiotech (stock options for an RA project), Consultant of: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer. Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech, Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, Andrew Blauvelt Speakers bureau: AbbVie, UCB, Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome, Grant/research support from: AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma Investigator (payments made to my company),
Abstract Background: Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have an inadequate response to or are intolerant to methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated the effectiveness and safety of intravenous golimumab+MTX vs golimumab monotherapy in RA patients. Methods: AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared the effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12; last observation carried forward was utilized for missing data. Safety was monitored through approximately 1 year. Results: Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab monotherapy, golimumab+MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean±standard deviation (SD) baseline CDAI scores were similar (30.8±15.1 and 32.6±15.4). Mean±SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab+MTX (-10.2±14.2 and -10.8±13.8) and golimumab monotherapy (-9.6±12.9 and -9.9±13.1). The incidence of adverse events/100 patient-years(PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab+MTX and 191.2 (176.2, 207.1) golimumab monotherapy; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) with golimumab+MTX vs 5.1 (2.9, 8.3) with golimumab monotherapy; none were considered serious. For golimumab+MTX vs golimumab monotherapy, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) vs 7.0 (4.4, 10.6), 0.9 (0.28, 2.03) vs 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) vs 1.0 (0.20, 2.79), respectively. Conclusions: Changes in CDAI score with golimumab monotherapy was generally similar to that of golimumab+MTX through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions. Trial registration: clinicaltrials.gov NCT02728934 05/04/2016
Abstract Background/Aims Ixekizumab (IXE) is a high-affinity, monoclonal antibody targeting IL-17A and is approved for the treatment of psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. We report long-term, end-of-study-program, safety outcomes in adult patients with PsO, PsA and axSpA who received at least one dose of IXE over 5 years (PsO) or 3 years (PsA and axSpA). Methods An integrated safety analysis consisting of data from 25 randomised clinical trials (RCTs; 17 PsO, 4 PsA, 4 axSpA) was used to examine long-term safety of IXE. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for all pooled studies by years of therapy and overall through March 2022, and reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at successive year intervals. Additional safety outcomes included selected safety topics of interest (among others). Results A total of 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, with a cumulative IXE exposure of 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA were included in this analysis. The IRs per 100 PY for any TEAE were as follows: patients with PsO=32.5; PsA=50.3; axSpA=38.0. The most commonly reported TEAEs were nasopharyngitis (PsO, IR = 8.8; PsA, IR = 9.0; axSpA IR = 8.4) and upper respiratory tract infection (PsO, IR = 6.2; PsA, IR = 8.3; axSpA IR = 5.8). Serious AEs were reported by 969 patients with PsO (IR = 5.4), 134 patients with PsA (IR = 6), and 101 patients with axSpA (IR = 4.8). Forty-five deaths were reported (PsO=36 [IR = 0.2]; PsA=6 [IR = 0.3]; axSpA=3 [IR = 0.1]). The IRs per 100 PY of discontinuation from the study drug due to AE were as follows: PsO, 2.9; PsA, 5.1; axSpA, 3.1. IRs of injection site reactions were: PsO, 5.9; PsA, 11.6; axSpA, 7.4. IRs of allergic reactions were: PsO, 5.6; PsA, 4.5; axSpA, 4.2. IRs of serious infections were low (PsO, IR = 1.3; PsA, IR = 1.2; axSpA, IR = 1.1). IRs of Candida were low across all indications (PsO, 1.9; PsA, 2.0; axSpA, 1.2), as were IRs of opportunistic infections (PsO, 1.8; PsA, 1.8; axSpA, 1.3). IRs were also low across all indications for depression, major adverse cerebro-cardiovascular events and malignancies (all IRs ≤1.6). Cases of inflammatory bowel disease (IBD) were uncommon (IRs ≤0.8 across indications). Conclusion In this updated analysis with 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA, IXE maintained a long-term safety profile up to 5 years, consistent with previous reports. Disclosure A. Deodhar: Grants/research support; A.D. received direct payments from Eli Lilly and Company as a scientific consultant/speaker, and payments (investigator) made to Oregon Medical Research Center. A. Blauvelt: Consultancies; A.B. received consulting fee from AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor. Member of speakers’ bureau; A.B. discloses direct payment for speaker bureaus from AbbVie, UCB. S. Schwartzman: Consultancies; S.S. is a consultant with AbbVie, Janssen, Lilly, Myriad, Novartis, Regeneron, Sanofi, UCB, Stelexis, Jubilant, and Teijin. Grants/research support; S.S. reports grants/contracts from Eli Lilly and Company, is a board member on the National Psoriasis Foundation Medical Board and part of the Scientific Advisory Board at Myriad. C. Salvarani: None. M. Feely: Shareholder/stock ownership; M.F. is an employee and shareholder at Eli Lilly and Company. Other; M.F. participated on a Data Safety Monitoring or Advisory Board at Eli Lilly and Company, is a Clinical Instructor in Dermatology at Mount Sinai and discloses previous employment with MC Medical Group, reimbursement of fees from Eli Lilly and Company and from Advisory Boards at the DREAM USA South Beach Symposium, is a current member of the AAD Investment Committee, Prevention Medical Review Board and ASDS Social Media Ambassador, and former member of the WDS Practice Advisory Committee, WDS Finance and Investment Committee, WDS Fundraising and Philanthropic Activities Committee, and former AAD Media Expert Team member and NPF Social Ambassador. A. Kronbergs: Shareholder/stock ownership; A.K. is an employee and shareholder at Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N.E. is an employee and shareholder at Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D.Z. is an employee and shareholder at Eli Lilly and Company. E. Mevel: Shareholder/stock ownership; E.M. is an employee and shareholder at Eli Lilly and Company. T. Holzkaemper: Shareholder/stock ownership; T.H. is an employee and shareholder at Eli Lilly and Company. E. Krishnan: Shareholder/stock ownership; E.K. is an employee and shareholder at Eli Lilly and Company. M. Lebwohl: Consultancies; M.L. also reports consulting fees from AnaptysBio, Arcutis, Inc., Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BioMX, Boehringer-Ingelheim, Brickell Biotech, Castle Biosciences,, Corevitas, Dermavant Sciences, Evommune, Inc., Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd., Meiji Seika Pharma, Mindera, National Society of Cutaneous Medicine, New York College of Podiatric Medicine, Pfizer, Seanergy, SUN Pharma, Verrica, and Vial. Grants/research support; M.L. reports grants/contracts from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc. P. Rahman: Consultancies; P.R. received consulting fees from AbbVie, Janssen, Novartis, Eli Lilly and Company and Pfizer. Grants/research support; P.R. discloses grants or contracts received from Janssen and Novartis. H. Marzo-Ortega: Consultancies; H.M-O. also discloses consulting fees from Abbvie, Eli Lilly and Company, Janssen, Moonlake, Novartis, Pfizer, and UCB. Honoraria; H.M-O. discloses payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Biogen, Eli-Lilly, Janssen, Novartis, Pfizer, and UCB. Grants/research support; H.M-O. discloses grants or contracts received from Janssen, Novartis and UCB. Other; H. M-O. additionally discloses support for attending meetings and/or travel from UCB, participation on a Data Safety Monitoring Board or Advisory Board at Pfizer, leadership or fiduciary role in other board, society (paid or unpaid) in the Executive Committee ASAS, the Medical Advisory Board of NASS and as Chair of the British Society for Spondyloarthritis. C. Bullock: Shareholder/stock ownership; C. Bullock is an employee and minor shareholder in Lilly.
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