scholarly journals Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up

Rheumatology ◽  
2019 ◽  
Vol 59 (2) ◽  
pp. 292-302 ◽  
Author(s):  
Roy Fleischmann ◽  
Mark C Genovese ◽  
Yong Lin ◽  
Gregory St John ◽  
Désirée van der Heijde ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Group Treatment ◽  
Human Monoclonal Antibody ◽  
Incidence Rates ◽  
Major Adverse Cardiovascular Events ◽  
Combination Group ◽  
Integrated Analysis ◽  
Open Label ◽  
Increased Risk

Abstract Objective Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-α. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions. Methods Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed. Results 2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts <1000 cells/mm3 were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time. Conclusion The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.

scholarly journals Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database

2021 ◽  
pp. annrheumdis-2021-221276
Author(s):  
Peter C Taylor ◽  
Tsutomu Takeuchi ◽  
Gerd R Burmester ◽  
Patrick Durez ◽  
Josef S Smolen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitor ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Phase Iii ◽  
Major Adverse Cardiovascular Events ◽  
Integrated Analysis ◽  
Link Type ◽  
Serious Infections

ObjectiveTo report long-term safety from the completed extension trial of baricitinib, an oral selective Janus kinase inhibitor, in patients with active rheumatoid arthritis (RA).MethodsTreatment-emergent adverse events are summarised from an integrated database (9 phase III/II/Ib and 1 long-term extension) of patients who received any baricitinib dose (All-bari-RA). Standardised incidence ratio (SIR) for malignancy (excluding non-melanoma skin cancer (NMSC)) and standardised mortality ratio (SMR) were estimated. Additional analysis was done in a subset of patients who had ever taken 2 mg or 4 mg baricitinib.Results3770 patients received baricitinib (14 744 patient-years of exposure (PYE)). All-bari-RA incidence rates (IRs) per 100 patient-years at risk were 2.6, 3.0 and 0.5 for serious infections, herpes zoster and major adverse cardiovascular events (MACE), respectively. In patients aged ≥50 with ≥1 cardiovascular risk factor, the IR for MACE was 0.77 (95% CI 0.56 to 1.04). The IR for malignancy (excluding NMSC) during the first 48 weeks was 0.6 and remained stable thereafter (IR 1.0). The SIR for malignancies excluding NMSC was 1.07 (95% CI 0.90 to 1.26) and the SMR was 0.74 (95% CI 0.59 to 0.92). All-bari-RA IRs for deep vein thrombosis (DVT)/pulmonary embolism (PE), DVT and PE were 0.5 (95% CI 0.38 to 0.61), 0.4 (95% CI 0.26 to 0.45) and 0.3 (95% CI 0.18 to 0.35), respectively. No clear dose differences were noted for exposure-adjusted IRs (per 100 PYE) for deaths, serious infections, DVT/PE and MACE.ConclusionsIn this integrated analysis including long-term data of baricitinib from 3770 patients (median 4.6 years, up to 9.3 years) with active RA, baricitinib maintained a similar safety profile to earlier analyses. No new safety signals were identified.Trial registration numberNCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT02265705, NCT01721044, NCT01721057, NCT01711359 and NCT01885078.

scholarly journals Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials

2013 ◽  
Vol 74 (1) ◽  
pp. 96-103 ◽  
Author(s):  
V P Bykerk ◽  
J Cush ◽  
K Winthrop ◽  
L Calabrese ◽  
O Lortholary ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Certolizumab Pegol ◽  
Safety Data ◽  
Steering Committee ◽  
Incidence Rates ◽  
Integrated Analysis ◽  
Open Label ◽  
Non Melanoma Skin Cancer ◽  
Randomised Controlled

ObjectiveTo report the long-term safety data of certolizumab pegol (CZP) in rheumatoid arthritis (RA) accumulated as of 30 November 2011.DesignData from 10 completed randomised controlled trials (RCT) of CZP in RA and several open-label extensions (OLE) were pooled across all doses. Reported adverse events (AE) occurred between the first dose and 84 days after the last dose. All deaths, serious infectious events (SIE) and malignancies were reviewed by external experts, classified according to predefined rules, and validated by an external steering committee. Incidence rates (IR) and event rates (ER) per 100 patient-years (PY) are presented.Results4049 RA patients who received CZP were included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years (range 0.04–7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most common serious AE, occurring more frequently in CZP compared to placebo-treated patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65 to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER 4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and 70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY), including five lymphomas (IR 0.05/100 PY).ConclusionsNo new or unexpected safety signals associated with CZP emerged in this updated long-term safety analysis. While SIE rates were higher for CZP than for placebo in RCT, the rate decreased with continued exposure to CZP. These rates are consistent with data previously reported for CZP and other tumour necrosis factor inhibitors.

scholarly journals Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial

2011 ◽  
Vol 70 (10) ◽  
pp. 1826-1830 ◽  
Author(s):  
Joel M Kremer ◽  
Anthony S Russell ◽  
Paul Emery ◽  
Carlos Abud-Mendoza ◽  
Jacek Szechinski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Incidence Rates ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Inadequate Responders

ObjectiveTo evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).MethodsPatients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.Results433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).ConclusionIn MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.

scholarly journals Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years

2021 ◽  
pp. annrheumdis-2021-221051
Author(s):  
Kevin L Winthrop ◽  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Alan Kivitz ◽  
Franziska Matzkies ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Link Type ◽  
Serious Infection ◽  
Grade 3 ◽  
Adjusted Incidence

ObjectiveTo characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.MethodsData were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets. We calculated exposure-adjusted incidence rates (EAIRs)/100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs).Results3691 patients received filgotinib for 6080.7 PYE (median 1.6, maximum 5.6 years). During the PBO-controlled period, TEAEs, including those of grade ≥3, occurred at comparable rates with filgotinib or PBO; long-term EAIRs of TEAEs grade ≥3 were 6.4 and 7.6/100PYE for FIL200 and FIL100. EAIRs for deaths were 0.6/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.5 and 0.3/100PYE for FIL200 and FIL100. EAIRs for serious infection were 3.9, 3.3 and 2.4/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.6 and 3.1/100PYE for FIL200 and FIL100. EAIRs for herpes zoster were 0.6, 1.1, and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.8 and 1.1/100PYE for FIL200 and FIL100. EAIRs for major adverse cardiovascular events were 0, 1.7 and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.4 and 0.6/100PYE for FIL200 and FIL100. No venous thromboembolism occurred during the PBO-controlled period; long-term EAIRs were 0.2 and 0/100PYE for FIL200 and FIL100.ConclusionsOver a median of 1.6 and maximum of 5.6 years of exposure, safety/tolerability of FIL200 and FIL100 were similar, with a lower incidence of infections with FIL200 among the long-term, as-treated dataset.

scholarly journals DOP61 Tofacitinib, an oral, small-molecule Janus kinase inhibitor, in the treatment of ulcerative colitis: Analysis of an open-label, long-term extension study with up to 5.9 years of treatment

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S100-S101 ◽  
Author(s):  
G R Lichtenstein ◽  
E V Loftus ◽  
S C Wei ◽  
A O Damião ◽  
D Judd ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Open Label ◽  
Mayo Score

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were demonstrated in patients with moderate to severe UC in 3 Phase 3 studies.1 Here, we present data from an ongoing, open-label, long-term extension (OLE) study.2 Methods We present updated safety and efficacy data from the OLE study (OCTAVE Open, NCT01470612; as of May 2019, database not locked). Eligible patients included non-responders (Week 8 data) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951) and completers (Week 52 data) or treatment failures (early-termination data) in OCTAVE Sustain (NCT01458574). Patients in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding [RB] subscore 0) at Week 52 of OCTAVE Sustain (central read) received tofacitinib 5 mg twice daily (BID); all others received 10 mg BID. Induction non-responders without clinical response (≥3-point and ≥30% decrease from induction study baseline total Mayo score, plus ≥1-point RB subscore decrease or absolute RB subscore ≤1) at Month 2 of the OLE study were withdrawn. Incidence rates (IRs) for adverse events (AEs) of special interest were calculated (no. of unique patients with events per 100 patient-years). Efficacy endpoints were derived from Mayo score (local read) with non-responder and last observation carried forward imputation (NRI-LOCF) [a]. Results Of 944 patients who received ≥1 dose of tofacitinib, 769 (81.5%) received 10 mg BID (median duration [range]: 5 mg BID 1170 [36–2066]; 10 mg BID 668 [1–2159] days). In total, 338 (35.8%) and 93 (9.9%) patients discontinued due to insufficient clinical response and AEs (excl. worsening UC), respectively. IRs (95% confidence interval) in the Tofacitinib. All group were: deaths 0.18 (0.05, 0.47); serious infections 1.57 (1.08, 2.19); herpes zoster (non-serious and serious) 3.27 (2.54, 4.14); major adverse cardiovascular events 0.14 (0.03, 0.40); malignancies excl. non-melanoma skin cancer (NMSC) 0.92 (0.56, 1.42); NMSC 0.74 (0.43, 1.21); deep vein thrombosis 0.05 (0.00, 0.25); pulmonary embolism 0.18 (0.05, 0.47) (Table). At Month 36 (NRI-LOCF), 58.9% (n = 103) and 33.5% (n = 257) were in remission, 64.6% (n = 113) and 37.0% (n = 284) had mucosal healing (Mayo endoscopic subscore of 0 or 1) [b] and 66.9% (n = 117) and 40.2% (n = 309) showed clinical response, in the 5 and 10 mg BID groups, respectively. Conclusion Incidence of AEs remained generally consistent in patients with moderate to severe UC in the OLE study compared with a previous analysis.2 Data continue to support long-term efficacy with tofacitinib up to 36 months beyond Week 52 of OCTAVE Sustain. References

scholarly journals Long-term safety and efficacy of sirukumab for patients with rheumatoid arthritis who previously received sirukumab in randomised controlled trials (SIRROUND-LTE)

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001465
Author(s):  
Daniel Aletaha ◽  
Clifton O Bingham ◽  
George Athanasios Karpouzas ◽  
Tsutomu Takeuchi ◽  
Carter Thorne ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Monoclonal Antibody ◽  
Group Versus ◽  
Signs And Symptoms ◽  
Major Adverse Cardiovascular Events ◽  
Safety And Efficacy ◽  
Serious Infection ◽  
Registration Number ◽  
Randomised Controlled

ObjectiveInterleukin (IL)-6 is a pleiotropic cytokine involved in the pathophysiology of rheumatoid arthritis (RA). Sirukumab is a human monoclonal antibody that binds to IL-6 with high affinity and specificity.MethodsThis long-term extension (LTE) study of the SIRROUND-D and SIRROUND-T studies assessed long-term safety and efficacy of sirukumab in adults with moderate-to-severe RA refractory to conventional disease-modifying antirheumatic drug therapy or antitumor necrosis factor agents. Patients received sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) or sirukumab 50 mg SC every 4 weeks (q4w).Results1820 patients enrolled in the LTE; median exposure was 2.34 and 2.07 years in sirukumab 50 mg q4w and 100 mg q2w groups, respectively. Adverse events (AEs) occurred in similar proportions between groups, with the exception of major adverse cardiovascular events (MACE), which were more common in the 50 mg q4w versus 100 mg q2w group (2.2% vs 1.0%), and injection-site reactions, more common in the 100 mg q2w group versus 50 mg q4w group (7.5% vs 3.7%). The most common serious AEs were infections (10% of the patients); 32 (1.8%) patients died during the study (primarily from serious infection and MACE). Malignancies were reported in 24 (1.3%) patients. Gastrointestinal perforations, hepatobiliary abnormalities and changes in laboratory parameters were rare. Reductions in RA signs and symptoms and improvements in physical function were maintained throughout the LTE.ConclusionsThe safety profile of sirukumab in the LTE remained consistent with that reported in SIRROUND-D and SIRROUND-T and efficacy was maintained.Trial registration numberNCT01856309.

scholarly journals O09 Safety profile of baricitinib for the treatment of RA up to 8.4 years: an updated integrated safety analysis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Kevin L Winthrop ◽  
Tsutomu Takeuchi ◽  
Gerd Burmester ◽  
Walter Deberdt ◽  
Douglas Schlichting ◽  
...  
Keyword(s):  
Safety Profile ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Stock Ownership ◽  
Research Support ◽  
Vein Thrombosis ◽  
Non Melanoma Skin Cancer ◽  
Deep Vein

Abstract Background/Aims  Baricitinib (BARI) is an oral selective inhibitor of Janus kinase (JAK)1/2, approved for treatment of moderate-to-severe- rheumatoid arthritis (RA) in adults. Here, we update the drug’s safety profile with data up to 8.4 years of treatment. Methods  Long-term safety of BARI was assessed from 9 completed randomized trials(5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension(LTE) study. Incidence rates(IRs) per 100 patient-years (PY) were calculated for all RA patients treated with ≥1 dose of BARI through 1-Sep-2019(All-BARI-RA set). IRs for deep vein thrombosis(DVT), pulmonary embolism(PE), and DVT and/or PE(DVT/PE) were also calculated for groups of patients while receiving BARI 2mg/4mg within All-BARI-RA. Major adverse cardiovascular events(MACE) were adjudicated in 5 Ph3 studies and the LTE. Results  3770 pts received BARI for 13,148 PY, with median and maximum exposure: 4.2 and 8.4 years, respectively. Overall IRs per 100 PY were: for any treatment-emergent adverse event (AE)(25.8); serious AE (including death)(7.2); temporary interruption due to AE (9.5); permanent discontinuation due to AE (4.8); death (0.52); serious infection (2.7); opportunistic infection (0.46)(excluding tuberculosis [TB], including multidermatomal herpes zoster [HZ]); TB (0.15); HZ (3.0); MACE (0.50); DVT (0.31); PE (0.24); DVT/PE (0.46); malignancies excluding non-melanoma skin cancer (NMSC)(0.91); NMSC (0.33); lymphoma (0.07); and gastrointestinal perforation (0.04). (IRs)[95% confidence intervals] for patients while receiving BARI 2mg (N = 1077) and BARI 4mg (N = 3400) were DVT 2mg (0.38)[0.18, 0.73] and 4mg (0.30)[0.21, 0.43]; PE 2mg (0.26)[0.09, 0.56] and 4mg (0.25)[0.16, 0.36]; and DVT/PE 2mg (0.47)[0.23, 0.84] and 4mg (0.46)[0.34, 0.61]. IRs for death tended to increase in later time intervals (beyond 192 weeks). No particular cause of death contributed to this increase. For all other safety topics of interest, across 48-week treatment intervals, IRs remained stable over time. Across safety topics, IRs were consistent with previous analyses. Conclusion  In this update, with 3021 additional PY of exposure, BARI maintained a safety profile similar to that previously reported, with no increase of IRs across safety topics through exposures up to 8.4 years. Disclosure  K.L. Winthrop: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and UCB Pharma. Grants/research support; Bristol Myers Squibb and Pfizer. T. Takeuchi: Consultancies; AbbVie, Asahi Kasei Medical, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis, Pfizer Japan, Taiho Pharmaceutical, Taiho Toyama Pharmaceutical, Takeda, and UCB Japan. G. Burmester: Consultancies; Eli Lilly and Company, Janssen, Novartis, and Pfizer. Grants/research support; Eli Lilly and Company. W. Deberdt: Shareholder/stock ownership; Eli Lilly and Company. D. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. D. Mo: Shareholder/stock ownership; Eli Lilly and Company. C. Walls: Shareholder/stock ownership; Eli Lilly and Company. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead Sciences, ILTOO Pharma, Janssen, MedImmune, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB Pharma. Grants/research support; AbbVie, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.

scholarly journals Patterns of multimorbidity and their effects on adverse outcomes in rheumatoid arthritis: a study of 5658 UK Biobank participants

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e038829
Author(s):  
Ross McQueenie ◽  
Barbara I Nicholl ◽  
Bhautesh D Jani ◽  
Jordan Canning ◽  
Sara Macdonald ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Outcome Measures ◽  
Primary Outcome ◽  
Adverse Outcomes ◽  
Major Adverse Cardiovascular Events ◽  
Uk Biobank ◽  
Long Term Conditions ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Clinical Records

ObjectiveTo investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA).DesignPopulation-based longitudinal cohort study.SettingUK Biobank.ParticipantsUK Biobank participants (n=502 533) aged between 37 and 73 years old.Primary outcome measuresPrimary outcome measures were risk of all-cause mortality and MACE.MethodsWe examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox’s proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor.Results75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports.ConclusionThose with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.

Atrial fibrillation associated with increased risk of venous thromboembolism

2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rates ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Deep Vein

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

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