Tumor Necrosis Factor Inhibitor Exposure Research Articles

Matching-Adjusted Indirect Comparison of the 52-Week Efficacy of Bimekizumab Versus Secukinumab and Ixekizumab for the Treatment of Radiographic Axial Spondyloarthritis.

A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. Individual patient data from BE MOBILE 2 (bimekizumab 160mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150mg), MEASURE 3 (secukinumab 300mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80mg were mostly non-significant, depending on the populations considered.

P167 Bimekizumab achieved sustained improvements in efficacy outcomes in patients with axial spondyloarthritis, regardless of prior tumour necrosis factor inhibitor treatment: week 52 pooled results from the phase 3 studies BE MOBILE 1 and BE MOBILE 2

Abstract Background/Aims Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL17A. In the phase 3 BE MOBILE 1 and 2 studies, BKZ treatment resulted in rapid and sustained improvements in efficacy outcomes through 52 weeks (wks) in patients with active nonradiographic axial spondyloarthritis (nr-axSpA) and radiographic (r)axSpA (i.e., ankylosing spondylitis [AS]). Here, we assess the efficacy of BKZ in tumour necrosis factor inhibitor (TNFi)-naïve or -inadequate responder (IR) patients with active nr-axSpA and raxSpA through Wk52. Methods In BE MOBILE 1 (nr-axSpA; NCT03928704) patients met Assessment of SpondyloArthritis international Society (ASAS) classification criteria and in BE MOBILE 2 (r-axSpA; NCT03928743) patients fulfilled modified New York and ASAS criteria. Patients were randomised to receive subcutaneous BKZ 160mg every 4wks (Q4W) or placebo (PBO) then BKZ 160mg Q4W from Wk16. This post-hoc analysis reports pooled mean efficacy data, including disease activity, MRI inflammation, physical function, and quality of life (QoL), through Wk52, stratified by TNFi status (naïve/IR). TNFi-IR patients were defined as those who experienced intolerance, or IR, to prior treatment given at an approved dose for ≥12wks. Results This pooled analysis included 505 TNFi-naïve and 81 TNFi-IR patients. 302/505 (59.8%) TNFi-naïve and 47/81 (58.0%) TNFi-IR patients were randomised to BKZ. Higher proportions of BKZ-randomised patients vs PBO achieved Wk16 ASAS40 (TNFinaïve: 46.0% vs 23.2%, TNFi-IR: 44.7% vs 14.7%; multiple imputation) and AS Disease Activity Score (ASDAS) <2.1 or low disease activity (47.9% vs 20.3%, 30.2% vs 15.6%; observed case). In continuous BKZ-treated patients, responses increased to Wk52 (ASAS40: 59.9%, 55.3%; ASDAS<2.1: 62.0%, 54.1%). Greater reductions from baseline in ASDAS-CRP and MRI inflammation by Wk16 were achieved with BKZ vs PBO in both TNFi-naïve/-IR patients; in continuous BKZ-treated patients this was sustained or further improved through 52wks. Comparable improvements in physical function, nocturnal spinal pain and ASQoL were observed through 52wks with BKZ in TNFinaïve/-IR patients (Table). Conclusion Across the full axSpA disease spectrum, BKZ treatment resulted in clinically relevant improvements in key efficacy outcomes vs PBO, including suppression of inflammation and improvements in physical function and QoL, regardless of prior TNFi exposure. Improvements were sustained to Wk52. Disclosure M. Magrey: Consultancies; AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, BMS and UCB Pharma. M. Van de Sande: Consultancies; AbbVie, Novartis and UCB Pharma. Member of speakers’ bureau; Janssen, Novartis and UCB Pharma. Grants/research support; Eli Lilly, Novartis and UCB Pharma. M. Breban: Consultancies; Novartis and UCB Pharma. Grants/research support; MSD. F. Van den Bosch: Consultancies; AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Janssen, Merck, Novartis, Pfizer and UCB Pharma. C. Fleurinck: Other; Employee of UCB Pharma. U. Massow: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Vaux: Other; Employee of UCB Pharma. X. Baraliakos: Consultancies; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. Grants/research support; Novartis and UCB Pharma. Other; Paid instructor for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. H. Marzo-Ortega: Consultancies; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Honoraria; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Grants/research support; Janssen, Novartis and UCB Pharma.

Using pooled electronic health records data to conduct pharmacoepidemiology safety studies: Challenges and lessons learned.

We assessed the suitability of pooled electronic health record (EHR) data from clinical research networks (CRNs) of the patient-centered outcomes research network to conduct studies of the association between tumor necrosis factor inhibitors (TNFi) and infections. EHR data from patients with one of seven autoimmune diseases were obtained from three CRNs and pooled. Person-level linkage of CRN data and Centers for Medicare and Medicaid Services (CMS) fee-for-service claims data was performed where possible. Using filled prescriptions from CMS claims data as the gold standard, we assessed the misclassification of EHR-based new (incident) user definitions. Among new users of TNFi, we assessed subsequent rates of hospitalized infection in EHR and CMS data. The study included 45 483 new users of TNFi, of whom 1416 were successfully linked to their CMS claims. Overall, 44% of new EHR TNFi prescriptions were not associated with medication claims. Our most specific new user definition had a misclassification rate of 3.5%-16.4% for prevalent use, depending on the medication. Greater than 80% of CRN prescriptions had either zero refills or missing refill data. Compared to using EHR data alone, there was a 2- to 8-fold increase in hospitalized infection rates when CMS claims data were added to the analysis. EHR data substantially misclassified TNFi exposure and underestimated the incidence of hospitalized infections compared to claims data. EHR-based new user definitions were reasonably accurate. Overall, using CRN data for pharmacoepidemiology studies is challenging, especially for biologics, and would benefit from supplementation by other sources.

Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of “Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate”

Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of “Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate”

S780 Impact of Ozanimod on Fecal Calprotectin Levels and the Association With Efficacy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 True North Study

Introduction: Ozanimod (OZA) is approved in the USA and EU for the treatment of moderate/severe ulcerative colitis (UC). OZA demonstrated efficacy in the phase 3 True North (TN) trial in patients (pts) with moderate/severe UC (NCT02435992). Infiltration of neutrophils in intestinal mucosa contributes to inflammation in inflammatory bowel diseases. Calprotectin, which is released by neutrophils, is a neutrophilic activity marker that is useful in monitoring UC disease activity. Methods: We assessed the effect of OZA on fecal calprotectin (FCP) levels and association with OZA efficacy in TN. During the 10-week (W) induction period, pts were randomized to double-blind (DB) OZA 0.92 mg or placebo (PBO) once daily (Cohort 1) or received open-label (OL) OZA once daily (Cohort 2). Pts with clinical response (CRS) to OZA at W10 were rerandomized to DB OZA or PBO for maintenance through W52. Efficacy endpoints (clinical remission, CRS, endoscopic improvement, mucosal healing, and histologic remission) and FCP levels were assessed at W10 and W52. Results: Change in FCP from baseline (BL) to W10 was assessed in 517 pts who received DB OZA (n=347) or PBO (n=170) and 293 who received OL OZA. Pts on OZA demonstrated reductions from BL in FCP at W10; this was significant vs PBO (P< .001, both cohorts) (Table). FCP reductions were significantly greater in pts with vs without CRS at W10 in all treatment groups (P< .001, all groups). Change in FCP from BL to W52 was assessed in 149 pts remaining on OZA and 109 who switched to PBO. FCP levels remained low through W52; pts on continuous OZA had significantly greater FCP reductions at W52 vs pts who switched to PBO (P=.0002). FCP reductions were significantly greater in pts with vs without CRS at W52 in OZA-OZA and OZA-PBO groups (P< .01, for both). Significantly greater reductions from BL in FCP occurred with OZA vs PBO at W10 and W52 regardless of prior biologic or tumor necrosis factor inhibitor exposure (P< .05, all groups). BL FCP level was predictive for CRS and histologic remission at W10 (P< .05, both endpoints). Reduction from BL in FCP at W10 was predictive and prognostic for all endpoints except CRS at W52 (P< .05, all endpoints). Conclusion: OZA treatment led to FCP reductions, indicative of decreases in intestinal neutrophil levels. BL FCP was predictive for OZA response. FCP reductions were predictive for OZA response and prognostic for UC. These findings may support use of FCP as a predictive biomarker for OZA response and prognostic biomarker in UC. Table 1. - Change from baseline in FCP at Weeks 10 and 52 FCP adjusted mean percent change (95% CI) Induction (Week 10) Maintenance (Week 52) Cohort 1 Cohort 2 Placebo (n=170) Ozanimod (n=347) Ozanimod (n=293) Ozanimod-placebo (n=109) Ozanimod-ozanimod (n=149) All patients 18.8 (-11.6, 59.6) -59.3 (-67.1, -49.7) -71.6 (-77.2, -64.5) -70.7 (-79.6, -57.7) -87.7 (-91.0, -83.3) Responders a -48.7 (-68.7, -16.0) -83.9 (-87.8, -78.8) -86.2 (-89.5, -81.8) -81.5 (-87.8, -71.7) -91.0 (-93.7, -87.1) Nonresponders b 54.9 (12.4, 113.5) -12.1 (-32.4, 14.4) -33.3 (-50.9, -9.5) -10.5 (-53.6, 72.9) -75.4 (-85.9, -57.2) aResponders during induction are pts who achieved CRS at W10, and responders during maintenance are pts who achieved CRS at W52.bNonresponders during induction are pts who did not achieve CRS at W10 and nonresponders at W52 did not achieve CRS at W52.

Incidence Rates of Psoriasis in Children With Inflammatory Bowel Disease and Juvenile Arthritis Treated With Tumor Necrosis Factor Inhibitors and Disease-Modifying Antirheumatic Drugs.

To estimate the differential effect of tumor necrosis factor inhibitor (TNFi) therapies and presence or absence of conventional synthetic disease-modifying antirheumatic drugs (DMARDs) on the incidence of psoriasis (PsO) in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic nonbacterial osteomyelitis (CNO). This was a retrospective cohort study from 2008 to 2020. TNFi and DMARD exposures were dichotomized as ever/never. The primary outcome was incident PsO. Incidence rates (IRs) of PsO were stratified by underlying diagnosis, TNFi agent, and DMARD use. Poisson regression was used to assess the IR ratios (IRRs) between exposure groups. There were 5088 children who met the inclusion criteria: 3794 (75%) had IBD, 1189 (23%) had JIA, and 105 (2%) had CNO. Of the 2023 children with TNFi exposure, 613 (30%) and 1410 (70%) were with or without a DMARD, respectively. When controlling for DMARD, sex, and family history of PsO, the IRR of developing PsO in patients exposed to adalimumab (ADA) was 2.70 times higher (95% CI 1.53-4.75; P < 0.001) than those who did not receive any TNFi treatment. IRR was lower, but not significantly different, for patients exposed to infliximab (IFX; IRR 2.34, 95% CI 1.56-3.51; P < 0.001) and etanercept (ETN; IRR 2.21; 95% CI 1.17-4.21; P = 0.006) compared to TNFi-unexposed patients. IRR of TNFi exposure was lower by 0.25 (P < 0.001) in DMARD-exposed patients compared to non-DMARD-exposed patients. IRR of TNFi-induced PsO was not significantly different among ADA, IFX, and ETN. However, for patients with exposure to any of the TNFi evaluated, the IRR was significantly lower in those also exposed to a DMARD.

Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery

Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery. We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn's & Colitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P < .05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration. A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P= .469) and SSI (12.0% vs 12.6%, P= .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI. Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

TNFi Cycling Versus Changing Mechanism of Action in TNFi-Experienced Patients: Result of the Corrona CERTAIN Comparative Effectiveness Study.

ObjectiveComparative effectiveness research can inform treatment decisions regarding the choice of biologics for rheumatoid arthritis (RA). The objective of this study is to compare the efficacy of tumor necrosis factor inhibitors (TNFis) and non‐TNFis (nTNFis) in real‐world patients with RA and past TNFi experience.MethodsComparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) was nested within the United States Corrona registry. Adult patients with RA with moderate to high disease activity (Clinical Disease Activity Index [CDAI] >10) with exposure to one or more prior TNFis who were switching to a new TNFi or nTNFi (choice of therapy per physician choice) were enrolled. The primary outcome was the achievement of low disease activity (LDA) at 12 months (CDAI ≤10; disease activity score in 28 joints based on C‐reactive protein [DAS28‐CRP] <2.67). Propensity score modeling probability of treatment with nTNFi versus TNFi adjusted for imbalanced factors. The response rate was modeled using mixed‐effect logistic regression models, adjusting for a priori and imbalanced baseline factors and accounting for the practice‐related treatment patterns.ResultsAfter applying inclusion criteria, 939 biologic initiations were analyzed, 505 (53.7%) nTNFis and 434 (46.3%) TNFis. Patients who started nTNFis were significantly more likely to have longer disease duration, more prior TNFi use, and higher patient fatigue scores and were more likely to have government insurance. At 12 months, 28% of nTNFi and 24% of TNFi initiators were in LDA by CDAI, and 22% of nTNFi and 19% of TNFi initiators were in LDA by DAS28‐CRP. After multivariable adjustment and controlling for the influence of site‐related confounding, there were no significant differences in the likelihood to reach LDA by CDAI (adjusted odds ratio [aOR] = 1.12; 95% confidence interval [CI], 0.78‐1.62) or DAS28‐CRP (aOR = 1.16; 95% CI, 0.77‐1.75).ConclusionIn this large, real‐world study enrolling patients with RA with prior TNFi exposure, switching to an nTNFi biologic was comparable in its clinical effectiveness with switching to another TNFi.

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

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...

Antitumour necrosis factor therapy is associated with de novo Crohn's disease after ileal pouch-anal anastomosis.

Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. A prospective single-centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25-year period ending July 2018. Patients with preoperative CD or IBD-unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. The study cohort consisted of 400 patients with a median follow-up of 44.0 (IQR 11-113) months. Sixty-two (16%) patients developed de novo CD 28.0 (IQR 6-67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5-year increase; P=0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P=0.011). This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.

Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The present study was undertaken to investigate the effectiveness and safety of dose reduction of tumor necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (SpA) compared to usual care. We searched the Cochrane Central Register of Controlled Trials, Embase, Medline, and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random-effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure, and follow-up duration. Outcomes of interest were Assessment of SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse, and safety. We included 6 randomized trials with 747 participants (442 with ankylosing spondylitis and 305 with nonradiographic axial SpA). Compared to the standard dose, there were fewer events with the reduced dose for the ASAS criteria for 40% improvement (risk ratio [RR] 0.62 [95% confidence interval (95% CI) 0.49, 0.78]) and for ASAS partial remission (RR 0.17 [95% CI 0.06, 0.46]). There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35 [95% CI 0.10, 0.60]) and no difference in C-reactive protein levels (MD 0.16 [95% CI -0.76, 1.07]) with the reduced dose. There were more disease flares/relapses (RR 1.73 [95% CI 1.32, 2.27]) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98 [95% CI 0.76, 1.25]) or injection/infusion reactions (IRR 0.71 [95% CI 0.42, 1.19]). Patients with axial SpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.

Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced

ObjectiveEvaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year.MethodsAdults who met ClASsification criteria for...

Psoriasis Associated With Tumor Necrosis Factor Inhibitors in Children With Inflammatory Diseases.

To estimate the incidence rate (IR) of psoriasis in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic noninfectious osteomyelitis (CNO) with tumor necrosis factor inhibitor (TNFi) exposure as compared to children without TNFi exposure and to the general pediatric population. This was a single-center retrospective cohort study of children with IBD, JIA, or CNO from 2008 to 2018. TNFi exposure was defined as a prescription for adalimumab, etanercept, infliximab, certolizumab, or golimumab, and the primary outcome was incident psoriasis. IRs and standardized incidence ratios (SIRs) were calculated. Cox proportional hazards models were used to assess the association of psoriasis with TNFi exposure and other risk factors. Of the 4,111 children who met inclusion criteria, 1,614 (39%) had TNFi exposure and 2,497 (61%) did not, with 4,705 and 6,604 person-years of follow-up, respectively. There were 58 cases (IR 12.3 per 1,000 person-years) and 25 cases (IR 3.8 per 1,000 person-years) of psoriasis in children with and without TNFi exposure, respectively. The SIR was 18 (95% confidence interval [95% CI] 15-22) overall, 30 (95% CI 23-39) for children with TNFi exposure, and 9.3 (95% CI 6.3-14) for children without TNFi exposure. The hazard ratio of psoriasis comparing TNFi exposure to no TNFi exposure was 3.84 (95% CI 2.28-6.47; P < 0.001). Children with IBD, JIA, and CNO had an increased rate of psoriasis compared to the general pediatric population, with the highest rate in those with TNFi exposure.

Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort

ObjectiveTo compare effectiveness of treatment with secukinumab (SEC) with that of alternative tumour necrosis factor inhibitors (TNFis) in patients with axial spondyloarthritis (axSpA) after withdrawal from one or more TNFis.MethodsPatients...

Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events

Tumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood. To evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events. A nested case-control study was conducted using the medical records of patients with autoimmune diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida) between January 1, 2003, and February 20, 2019. Patients were included if their records reported International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnostic codes for US Food and Drug Administration-approved autoimmune disease indication for TNF inhibitor use (ie, rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn disease, and ulcerative colitis) and diagnostic codes for inflammatory CNS events of interest. Patients were matched 1:1 with control participants by year of birth, type of autoimmune disease, and sex. TNF inhibitor exposure data were derived from the medical records along with type of TNF inhibitor, cumulative duration of exposure, and time of exposure. The main outcome was either inflammatory demyelinating (multiple sclerosis and other diseases such as optic neuritis) or nondemyelinating (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis) CNS event. Association with TNF inhibitor was evaluated with conditional logistic regression and adjusted for disease duration to determine the odds ratios (ORs) and 95% CIs. Secondary analyses included stratification of outcome by inflammatory demyelinating and nondemyelinating CNS events and by autoimmune disease (rheumatoid arthritis and non-rheumatoid arthritis). A total of 212 individuals were included: 106 patients with inflammatory CNS events and 106 control participants without such events. Of this total, 136 were female (64%); the median (interquartile range) age at disease onset for patients was 52 (43-62) years. Exposure to TNF inhibitors occurred in 64 patients (60%) and 42 control participants (40%) and was associated with an increased risk of any inflammatory CNS event (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). These results were similar when the outcome was stratified by demyelinating and nondemyelinating CNS events. Secondary analyses found the association was predominantly observed in patients with rheumatoid arthritis (adjusted OR, 4.82; 95% CI, 1.62-14.36; P = .005). This study found that exposure to TNF inhibitors in patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Whether this association represents de novo or exacerbated inflammatory pathways requires further research.

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis.

To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models. Twenty-four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors (TNFi), 8 involved nonsteroidal antiinflammatory drugs (NSAIDs), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), was not significantly different between TNFi-treated and biologics-naive patients at 2 years (mSASSS difference -0.73 [95% confidence interval (95% CI) -1.52, 0.12], I2 = 28%) and ≥4 years (mSASSS difference -2.03 [95% CI -4.63, 0.72], I2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNFi-treated and biologics-naive patients at ≥4 years (mSASSS difference -2.17 [95% CI -4.19, -0.15]). No significant difference in spinal radiographic progression was observed between NSAID-treated and control patients (mSASSS difference -0.30 [95% CI -2.62, 1.31], I2 = 71%) or between secukinumab-treated and biologics-naive patients (mSASSS difference -0.34 [95% CI -0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. Although no significant protective effect of TNFi treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNFi after ≥4 years. Therefore, long-term TNFi exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long-term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Tuberculosis among patients treated with TNF inhibitors for rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis in Slovenia: a cohort study

ObjectivesThis study aimed to assess the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with any of the commercially available...

Liver enzyme elevation in patients with ankylosing spondylitis treated with tumor necrosis factor inhibitors: a single-center historical cohort study.

Background/AimsTumor necrosis factor inhibitors (TNFi) have been known to induce liver enzyme elevation, sometimes associated with viral reactivation or toxic hepatitis. We evaluated the incidence and risk factors of TNFi-associated liver enzyme elevation in Korean ankylosing spondylitis (AS) patients who previously had normal liver enzymes.MethodsRetrospectively, we collected data from the records of 363 AS patients treated with TNFi at a tertiary hospital from 2003 to 2017. Liver enzyme elevation was defined as abnormal elevation of aspartate aminotransferase and/or alanine aminotransferase levels on two or more consecutive visits. Patients with previously diagnosed liver disease were excluded.ResultsThe incidence of liver enzyme elevation was 23.7% (occurring in 86 of 363 patients). The median duration of TNFi exposure before liver enzyme elevation was 3.72 months (interquartile range, 1.77 to 12.51). There was no difference in the occurrence of liver enzyme elevation with concomitant disease-modifying anti-rheumatic drugs and TNFi compared to TNFi alone (23.9% vs. 23.6%). In multivariate analysis, the hazard ratios for liver enzyme elevation were 4.62 (95% confidence interval [CI], 1.43 to 15.01) for male sex, 4.06 (95% CI, 2.11 to 7.84) for underlying non-alcoholic fatty liver disease, and 2.53 (95% CI, 1.38 to 4.64) for hyperlipidemia. After switching to another TNFi, the liver enzyme elevation was not normalized in nine of 13 patients.ConclusionsLiver enzyme elevation was observed in a quarter of patients with AS receiving a TNFi. Male sex, non-alcoholic fatty liver disease, and hyperlipidemia were independent risk factors for liver enzyme elevation. Switching to another TNFi had a limited effect on restoring normal liver enzyme levels.

Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial

Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis. IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523. Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B. Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis. AbbVie and Boehringer Ingelheim.

Tumour necrosis factor inhibitor exposure and radiographic outcomes in Veterans with rheumatoid arthritis: a longitudinal cohort study.

The aim was to estimate the impact of TNF inhibitor (TNFi) exposure on radiographic disease progression in US Veterans with RA during the first year after initiating therapy. This historical longitudinal cohort design used clinical and claims data to evaluate radiographic progression after initiation of TNFi. US Veterans with RA initiating TNFi treatment (index date), ≥ 6 months pre-index and ≥ 12 months post-index VA enrolment/activity, and initial (6 months pre-index to 30 days post-index) and follow-up (10-18 months post-index) bilateral hand radiographs were eligible. The cumulative TNFi exposure and change in modified Sharp score (MSS) between initial and follow-up radiographs were calculated. The percentage of patients with clinically meaningful change in MSS (≥ 5) for each month of exposure was assessed using a longitudinal marginal structural model with inverse probability of treatment weights. Mean values and CIs were generated using 1000 bootstrapped samples. For 246 eligible patients, the mean (s.d.) age was 58 (11) years; 81% were male. The mean (s.d.) initial MSS was 19.6 (33.4) (range 0-214). The mean change (s.d.) in MSS was 0.3 (3.6) (median 0, range -19 to 22). Patients with the greatest exposure had the least radiographic progression for both crude and adjusted model analyses. Adjusted rates of MSS change ≥ 5 points (95% CI) were 10.6% (9.8%, 11.4%) for patients with 3 months of exposure compared with 5.4% (5.1%, 5.7%) for patients with 12 months of exposure. One-year changes in radiographic progression were small. Patients with the greatest cumulative TNFi exposure experienced the least progression.