TNF-α Inhibitor Therapy Research Articles

Impact of TNF-α inhibitor therapy on cardiovascular outcomes in ankylosing spondylitis: a nationwide population-based study.

This study aimed to evaluate the association between tumor necrosis factor-α inhibitor (TNFi) therapy and cardiovascular (CV) outcomes, as well as all-cause mortality, in patients with ankylosing spondylitis (AS). This retrospective cohort study included 24,986 patients newly diagnosed with AS between 2010-2019 without a history of CV diseases, using data from the Korean National Health Insurance Service. CV events were observed through the end of 2021. After exposure density sampling (1:1), we investigated the association among use of TNFi, duration of TNFi use, and risk of the composite CV outcome (ischemic stroke, heart failure, ischemic heart disease, or CV death) and all-cause mortality. Overall, TNFi users (N = 8,650) and non-users (N = 8,580) had a comparable risk of the composite CV outcome. However, prolonged TNFi use (≥ 1 year) was associated with a significantly lower risk of the composite CV outcome [adjusted hazard ratio (aHR): 0.72, 95% CI: 0.55-0.93, p = 0.012] and all-cause mortality (aHR: 0.37, 95% CI: 0.21-0.66, p < 0.001) compared to discontinued TNFi use (< 1 year), with adjustments made for age, sex, disease duration, hypertension, diabetes, hyperlipidemia, chronic kidney disease, non-steroidal anti-inflammatory drug (NSAID) use, body mass index (BMI), and smoking status. TNFi therapy did not reduce CV events in AS patients. However, long-term TNFi therapy is likely to be beneficial in reducing CV events and all-cause mortality compared to discontinuing TNFi therapy in patients with AS.

Plasma Cytokines for the Prediction of the Effectiveness of TNFα Inhibitors Etanercept, Infliximab, and Adalimumab in the Treatment of Psoriasis.

Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the "positive effect" and "no effect" groups, except for IL20, which was 2.61 times higher in the "positive effect" group compared to the "no effect" group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the "positive effect" group. The increase in ICAM1 in the "no effect" group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

Novel Pharmaceuticals and Therapeutics for Tumor Necrosis Factor-Alpha-Resistant Crohn's Disease: A Narrative Review.

Inflammatory bowel disease (IBD) is a medical condition that causes persistent, relapsing inflammation of the gastrointestinal tract. It is an umbrella term encompassing two different conditions: ulcerative colitis (UC) and Crohn's disease (CD). The standard treatment for patients with moderate to severe CD is tumor necrosis factor-α(TNF-α) inhibitors; however, a subset of CD patients face challenges in regardto this disease's treatment. Certain populations of patients with CD may exhibit resistance or develop tolerance to TNF-αinhibitor therapy over time. The recurrent gastrointestinal inflammation associated with CD can severely impact the quality of life and lead to complications for those suffering from this condition. The symptomatic flare-ups these subpopulations continue to experience underscores why such a need for alternative therapies is desperately needed. These alternative therapies not only offer potential benefits for those with TNF-αresistance, but CD may also serve as a superior therapy option for those trying to avoid the adverse effects of CD treatments available today. This review aims to explore and investigate the novel drugs and therapies that are being investigated for the treatment of TNF-αresistant CD, such as upadacitinib, risankizumab, vedolizumab, synbiotics, fecal microbiota transplantation (FMT), and stem cell therapy. Upadacitinib is a Janus kinase inhibitor, Risankizumab is a monoclonal antibody targeting interleukin-23, and Vedolizumab is an integrin receptor antagonist. The latest advancements in CD management have shown encouraging results. Some of these novel drugs and therapies not only offer a potential solution for CD patients exhibiting resistance to TNF-αinhibitors but may also provide a superior alternative for individuals prone to opportunistic infections.

MicroRNA-5196 as an Accurate Biomarker of Disease Activity and Response to Treatment in Rheumatoid Arthritis

Objective: Methods: One hundred patients divided into two groups’ 50 responders and 50 non responders with 50 healthy individuals were studied. The serum expression ofmiRNA-5196 was detected by using real-time polymerase chain reaction. Results: miRNA-5196 expression was significantly higher in rheumatoid arthritis patients versus control group P &lt;0.05. Sub-group of patients into responders and non-responders showed that miRNA-5196 expression higher in non-responders than responders.miRNA-5196 expression related with response to TNF-α inhibitor and disease activity in patients with rheumatoid arthritis. Conclusion: miRNA-5196 may consider as a valid target for monitoring progression of RA disease and response to TNF-α inhibitor therapy.

Safety and Efficacy of Golimumab in Indian Patients with Active Spondyloarthritis of Ankylosing Spondylitis or Psoriatic Arthritis: A Multicenter, Noncomparative, Open-Label, Real-World Study.

The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitor therapy for most common rheumatological diseases, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in controlled clinical trials is well-studied. This study evaluated subcutaneous (SC) golimumab in Indian patients with active spondyloarthritis (SpA) of AS or PsA in a real-world setting. This phase 4, multicenter, prospective, non-comparative, interventional, 24-week study was performed in patients (age ≥18 years) with active SpA of AS or PsA (NCT03733925). Golimumab 50 mg was given subcutaneously to the patients every 4 weeks. Safety was assessed. The proportion of patients with AS and PsA achieving ≥20% improvement in the Assessment of SpA International Society 20 (ASAS20) criteria and American College of Rheumatology 20 (ACR20) responses, respectively, at weeks 14 and 24 were efficacy endpoints. Of the 100 patients enrolled (men: 78 [78.0%]; mean age: 36.7 [12.02] years), 94 (94.0%) patients completed the study. Treatment-emergent adverse events with golimumab were observed in 29/100 (29.0%) patients, and nasopharyngitis and upper respiratory tract infection (5.0% each) were the most common (≥5%). Deaths were not reported. At week 14, 74.5% (95% confidence interval [CI]: 59.7; 86.1%) of patients with AS and 84.6% (95% CI: 69.5; 94.1%) of patients with PsA achieved ASAS20 and ACR20 responses, which were sustained at week 24 (ASAS20: 66.0% [95% CI: 50.7, 79.1%]; ACR20: 93.2% [95% CI: 81.3, 98.6%]), respectively. Golimumab (50 mg) administered subcutaneously was safe and effective in Indian patients with active SpA of AS or PsA during the 24-week study period with no new safety signals.

Effect of TNF-α Inhibitor Therapy on Growth of the Prostate Gland

BackgroundInflammation has been linked to the development of benign prostatic hyperplasia (BPH). SRD5A2 is a pivotal enzyme in the development and growth of the prostate gland and a critical target for BPH therapy. TNF-α regulates epigenetic changes in SRD5A2, leading to suppression of SRD5A2 gene and protein expression. It is unknown whether TNF-α inhibitor therapy affects prostate growth. ObjectiveTo evaluate the effect of TNF-α inhibitor therapy on prostate growth via analysis of measurements on serial pelvic imaging scans. Design, setting, and participantsIn this retrospective cohort study, we analyzed serial pelvic cross-sectional imaging (magnetic resonance imaging or computed tomography scans) for men aged ≥18 yr receiving TNF-α inhibitors. Our inclusion/exclusion criteria yielded a treatment cohort of 99 men. An age-matched cohort was constructed with the same inclusion/exclusion criteria but without TNF-α therapy (n = 99). Outcome measurements and statistical analysisProstate growth on serial pelvic cross-sectional imaging was the primary outcome measure. Results and limitationsThere was no significant difference in total prostate volume (TPV) at baseline between the two groups. The TNF-α treatment group had a lower mean TPV on follow-up (26.21 ± 9.43 vs 32.71 ± 18.89 cm3; p = 0.002) and a lower median prostate growth rate (−0.01 vs 0.68 cm3/yr; p = 0.001). A multivariable linear regression model adjusted for age, race, initial TPV, and body mass index also revealed a significantly lower growth rate for men in the treatment group. ConclusionTNF-α inhibitor use was negatively correlated with the prostate growth rate, suggesting that inflammatory mediators regulate prostate growth. Patient summaryWe examined prostate growth rates in men taking TNF-α inhibitors and found that these drugs have a shrinking effect on the prostate. We conclude that TNF-α inhibitors may impede prostate growth.

Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials

ObjectiveTo investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA).MethodsWe investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman’s correlation.ResultsC1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p < 0.05). Patients with AS Disease Activity Score C-reactive protein (ASDAS CRP) major improvement and/or clinically important improvement had significantly higher C1M, C3M, C4M, C6M, and PRO-C4 levels than patients with no/low improvement at baseline (all p < 0.05). Baseline levels of biomarkers showed weak to moderate correlations with ASDAS and structural damage scores.ConclusionECM metabolites showed a pharmacodynamic effect and were associated with ASDAS response during TNF-α inhibitor treatment in patients with axSpA.

Inflammatory Bowel Disease as a Paradoxical Reaction to Anti-TNF-α Treatment-A Review.

TNF-α inhibitors (TNFis) have revolutionized the treatment of certain chronic immune-mediated diseases, being widely and successfully used in rheumatic inflammatory diseases, and have also proved their efficacy in the treatment of inflammatory bowel disease (IBD). However, among the side effects of these agents are the so-called paradoxical effects. They can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition. A wide range of paradoxical effects have been reported including dermatological, intestinal and ophthalmic conditions. The causal mechanism of occurrence may implicate an imbalance of cytokines, but is still not fully understood, and remains a matter of debate. These paradoxical reactions often show improvement on discontinuation of the medication or on switching to another TNFi, but in some cases it is a class effect that could lead to the withdrawal of all anti-TNF agents. Close monitoring of patients treated with TNFis is necessary in order to detect paradoxical reactions. In this study we focus on reviewing IBD occurrence as a paradoxical effect of TNFi therapy in patients with rheumatological diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis).

Clinical Response to Tumor Necrosis Factor-α Inhibitor Therapy in the Management of Cardiac Sarcoidosis

Evidence that tumor necrosis factor-α (TNF-α) inhibitors may benefit patients with cardiac sarcoidosis (CS) is limited to small case series and both imaging and clinical outcomes in this population are not well known. This study aimed to evaluate the disease course of patients with CS treated with either infliximab or adalimumab therapy based on serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and clinical outcomes. An institutional CS research database was queried for patients treated with TNF-α inhibitors between 2016 and 2021. Outcomes included (1) change in mean prednisone dose, (2) FDG-PET improvement, and (3) unplanned hospitalizations, advanced heart failure therapies, or death. Our query yielded 31 patients with CS. A total of 13 patients were on infliximab, 15 patients were on adalimumab, and 3 patients were on adalimumab before transitioning to infliximab. Mean prednisone dose decreased between FDG-PET immediately preceding TNF-α and second after TNF-α FDG-PET (18.6±15.7mg to 7.7±12.4mg, p=0.018). A significant decrease was seen in the mean number of segments demonstrating FDG uptake between most recent pre-TNF-α and first after TNF-α inhibitor FDG-PET (mean segments=4.2 vs 3.1, p=0.048). Between earliest pre-TNF-α and first after TNF-α FDG-PET there was a numerical decrease in average myocardial maximum standard uptake values (SUVmax) (4.4 vs 3.1, p=0.18), and the ratio of SUVmax myocardium:SUVmax blood pool (1.9 vs 1.5, p=0.26). Within 36months of initiating TNF-α inhibitor, 4 patients (13%) experienced unplanned cardiovascular hospitalization (median time to hospitalization=12.1months). In conclusion, in patients with CS, TNF-α inhibitor therapy is associated with decreased glucocorticoid use, numerical decrease in cardiac FDG uptake, and minimal cardiac morbidity.

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases. The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis. Patients had discontinued one prior TNFαi (due to loss of efficacy, tolerability, or inconvenience) and were followed for 12 months after GLM initiation. Primary endpoints included the proportion of patients achieving low disease activity (LDA, DAS28-CRP<3.2) in RA, minimal disease activity (MDA, fulfilment of 5 of 7 outcome measures) in PsA, or low disease activity (ASDAS<2.1) in axSpA at 6 months. Disease activity at 3 and 12 months and quality of life (QoL; EQ-5D-3L) were also assessed. Adverse events were monitored. Protocol-specified analyses were based on observed data. In 712 patients, (n=325, RA; 186, PsA; 201, axSpA), mean age was 54 years, 64% were female, and median disease duration was 5 years. Primary endpoints were achieved in 58.3% (RA), 45.5% (PsA), and 45.4% (axSpA) of patients; disease activity improvements were observed at 3 and 12 months and EQ-5D-3L results showed improved QoL over time. The treatment persistence rate at 12 months was 67.8% of patients. No new safety signals were observed. This pooled analysis of the GO-BEYOND studies showed that treatment with GLM was effective and represented a valid second-line option for RA, PsA, and axSpA patients.

Blood Cell Biomarkers of Inflammation and Cytokine Levels as Predictors of Response to Biologics in Patients with Psoriasis.

For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) were measured in patients with psoriasis initiating TNF-α inhibitors (n = 131), IL-17/IL-17R inhibitors (n = 65), or IL-23/IL-12/23 inhibitors (n = 50). The blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-17A, IL-6, soluble IL-6 receptor (sIL-6R), and soluble IL-6 signal transducer (sIL-6ST) were measured in patients initiating adalimumab (n = 62) or IL-17/IL-17R inhibitors (n = 24). Treatment response was defined by a psoriasis area and severity index (PASI) ≤ 2 three months after treatment initiation. Responders to TNF-α inhibitors had a lower NLR at baseline than non-responders (median and interquartile range (IQR) 2.15 (1.67-2.86) vs. 2.54 (1.88-3.55); p = 0.04). Responders to treatment with adalimumab had lower IL-6 levels at baseline than non-responders (0.99 (0.42-1.4) vs. 1.62 (0.96-2.41) pg/mL; p = 0.02). For the majority of patients, the IL-17A, IL-1β, and IFN-γ levels were below quantification limits. NLR and IL-6 may serve as predictive biomarkers of treatment response to TNF-α inhibitor therapy in patients with psoriasis.

Travel related histoplasmosis – a diagnostic challenge in a patient with tumor necrosis factor alpha (TNF-α) inhibitor therapy

IntroductionIn a non-endemic setting, disseminated histoplasmosis is a rare travel-related health problem of immunosuppressed returnees from endemic regions.MethodsWe describe the case of a 68-year-old man with rheumatoid arthritis and tumor necrosis factor alpha (TNF-α) inhibitor treatment-related immunodeficiency, who suffered from disseminated histoplasmosis after traveling to Brazil. Based on this case, we discuss challenges and pitfalls associated with the diagnosis of disseminated histoplasmosis in a non-endemic setting.ResultsThe disease mimicked a hemophagocytic lymphohistiocytosis (HLH) like syndrome. Histoplasma capsulatum was microscopically detected in bronchoalveolar fluid and bone marrow aspirate smears, but was initially misclassified as Leishmania spp., another class of pathogens, which may cause HLH like syndromes in immunocompromised individuals.DiscussionSince the clinical symptoms of histoplasmosis are nonspecific and physicians in non-endemic regions might not be familiar with this disease pattern, there is a risk of delayed diagnosis of travel related cases. Taking a thorough travel history is key in unclear cases of illness in immunocompromised patients.

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis.

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism’s response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.

Clinical and economic analysis of biologic agents and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: cost per responder model

AIM. To compare the cost per responder (CPR) between different groups of biologic agents and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA). Materials and Methods. A total of 320 patients with RA were included in the study. Patients were divided into 4 groups (n=80 in each group): group 1 received B cell-depleting agent (rituximab), group 2 – TNF-alpha (α) inhibitors, group 3 –interleukin-6 inhibitor (tocilizumab), and group 4 – Janus kinase inhibitor (tofacitinib). The effectiveness of therapy was assessed using the generally accepted index of rheumatoid arthritis activity DAS28 and the dynamics of this index after 12 months of therapy. A good response on DAS28 (current DAS28 scores of 3.2 or less with reductions in DAS28 of more than 1.2) was accepted as a response to therapy. For the leading CPR-DAS28 drugs, an ad- ditional CPR study was performed using the SDAI, CDAI, and RAPID-3 indices. Results. A good response on DAS28 was observed more frequently in group 3 (56.3%) and group 4 (6.3%) compared to group 1 (11.5%, p&lt;0.05 in both cases) and group 2 patients (22.5%, p&lt;0.05 in both cases). CPR-DAS28 in group 3 was RUB 1094772.6, in group 4 – RUB 1089201.3; and that was 3.3 times lower than in group 1 (RUB 3587662.2, p&lt;0.05 in both cases) and 2.3 times lower than in group 4 (RUB 2545747.3, p&lt;0.05 in both cases). In group 3 (tocilizumab) CPR-SDAI was RUB 786867.9, CPR-CDAI – RUB 774285.7, and CPR-RAPID-3 – RUB 786867.9. In group 4 (tofacitinib) CPR-SDAI was RUB 1048831.2, CPR-CDAI – RUB 1088379.9, and CPR-RAPID – RUB 915730.8. Conclusion. CPR were lower with interleukin-6 inhibitor and Janus kinase inhibitor therapy than with B cell-depleting agent and TNF-α inhibitors therapy. Determination of CPR by SDAI, CDAI, and RAPID-3 indices revealed an advantage of interleukin-6 inhibitor therapy over Janus kinase inhibitor therapy.

Baseline serum biomarkers of inflammation, bone turnover and adipokines predict spinal radiographic progression in ankylosing spondylitis patients on TNF inhibitor therapy

ObjectiveTo analyze whether biomarker levels at baseline or their change after 3 months or 2 years predict radiographic spinal progression in ankylosing spondylitis (AS) patients treated with TNF-α inhibitors (TNFi). Methods137 AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included before starting TNFi. Serum biomarkers were measured at baseline, 3 months and 2 years: Markers of inflammation (calprotectin, matrix metalloproteinase-3, vascular endothelial growth factor), bone turnover markers (bone-specific alkaline phosphatase, serum C-terminal telopeptide fragments of type I collagen (sCTX), osteocalcin, osteoprotegerin, procollagen type I and II N-terminal propeptide, sclerostin) and adipokines (high-molecular-weight adiponectin, leptin, visfatin). Spinal radiographs were scored at baseline, 2 and 4 years. Logistic regression was performed to examine the association between biomarker values and radiographic spinal progression, adjusting for known risk factors for radiographic progression. ResultsBaseline calprotectin and visfatin levels were associated with mSASSS progression ≥2 points (OR 1.195 [95%CI 1.055–1.355] and 1.465 [1.137–1.889], respectively), while calprotectin was also associated with new syndesmophyte formation after 2 years (OR 1.107 [1.001–1.225]). Baseline leptin level was associated with mSASSS progression ≥4 points after 4 years (OR 0.614 [0.453–0.832]), and baseline sCTX level with syndesmophyte formation after 4 years (OR 1.004 [1.001–1.008]). Furthermore, change of visfatin and leptin levels over the first 2 years showed significant association with radiographic progression after 4 years. ConclusionIndependent of known risk factors, serum levels of biomarkers at baseline are able to predict radiographic spinal progression over 2 and 4 years in AS patients on TNFi therapy.

Association of Tumor Necrosis Factor α Inhibitor Use with Diagnostic Features and Mortality of Tuberculosis in the United States, 2010-2017.

BackgroundAn elevated risk of tuberculosis (TB) disease in persons who have received tumor necrosis factor alpha inhibitor medications (TNF-α inhibitors) has been reported for nearly two decades, but clinical diagnostic features and outcomes of TB in this population remain poorly described.MethodsWe analyzed national surveillance data for TB cases among persons aged 15 years and older reported in the United States during 2010–2017 and associated mortality data reported through 2019 to describe the clinical characteristics of those receiving TNF-α inhibitors.ResultsOf 70 129 TB cases analyzed, 504 (0.7%) of the patients had TNF-α inhibitor use reported at TB diagnosis. Patients with TNF-α inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF-α inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P < .001). Patients receiving TNF-α inhibitors were less likely to have acid-fast bacilli noted on sputum smear microscopy (25.6% vs 39.1%, P = .04), and more likely to have drug-resistant disease (13.5% vs 10.0%, P < .001). TB-attributed deaths did not significantly differ between patients receiving and not receiving TNF-α inhibitors (adjusted odds ratio, 1.46 [95% confidence interval, .95–2.26]).ConclusionsClinicians evaluating TNF-α inhibitor–treated patients should have a high index of suspicion for TB and be aware that extrapulmonary or sputum smear–negative TB disease is more common in these patients. No significantly diminished survival of TB patients treated with TNF-α inhibitor therapy before TB diagnosis was noted.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.

Paradoxical psoriasis in pediatric patients: A systematic review.

Paradoxical psoriasis occurs in pediatric patients following treatment with biologic agents. These presentations are not well described, and optimal treatment strategies have not been established. To describe the reported rates, demographic characteristics, clinical presentation, and treatment options for TNF-α inhibitor-induced psoriasis. Systematic review of published cases and cohort studies of paradoxical psoriasis induced by biologic agents, with specific reference to TNF-α inhibitors. We identified 4564 pediatric patients treated with TNF-α inhibitors, of whom 210 (4.6%) developed paradoxical psoriasis. Infliximab was the drug most likely to induce psoriasis (8.3%), followed by adalimumab (3.3%). Individual-level data were acquired from 129 individuals with a mean age of 13.6years (SD: 4.0); 45.0% were male. The scalp was the most commonly affected area (47.5%), followed by the ears (30.8%). Most (63.3%) patients were continued on TNF-α inhibitor therapy. Among those who switched TNF-α inhibitors, only 32.0% had complete clearance of their skin lesions. Among patients who were switched to a non-TNF-α inhibitor, 81% had complete clearance of their paradoxical psoriasis. Data were acquired from retrospective studies including case reports and case series. TNF-α inhibitor-induced psoriasis is a common adverse effect; however, most patients can continue their original therapy and be managed with skin-directed topical or systemic medications. If a patient requires medication discontinuation, switching to a new TNF-α inhibitor is unlikely to lead to resolution of their skin lesions.

THE EFFECTIVENESS OF TNF-Α INHIBITOR THERAPY IN BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: To evaluate the effectiveness of TNF-α inhibitor therapy in Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) patients compared to placebo, assessed using Global Response Assessment (GRA). Material &amp; Methods: A systematic review and meta-analysis. Subjects were patients with moderate to severe diagnosis of BPS/IC who were given TNF-α inhibitor versus placebo, with the Global Response Assessment (GRA) (patient-reported self-reported BPS/IC treatment response scale). A systematic literature search was carried out on the English databases PubMed/MEDLINE and Science Direct, published until September 2020. Data were extracted independently and assessed the bias and quality of each selected article. Results: Initially there were 124 studies. After further selection, 2 RCT studies were included in the criteria for this study. The number of samples obtained was 85 patients. There is 1 study that used 400 mg of certolizumab pegol subcutaneously and 1 study used adalimumab 80 mg subcutaneously and followed by 40 mg subcutaneously for 2 weeks. Both studies had statistically low heterogeneity with I2 = 0% (P = 0.34), so fixed effect statistical model was used to determine the result. Furthermore, there was no significant difference (P = 0.32) between the number of GRA responders from the TNF-α inhibitor and placebo therapy groups, with odds ratio of 1.61 (CI = 0.65-4.00). Conclusion: TNF-α inhibitor therapy did not increase GRA responders when compared to placebo.

P136 Efficacy and safety of olokizumab in a phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy

Abstract Background/Aims Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6. Here we present the results of the phase III study of OKZ in anti-TNF-IR patients. Methods Patients with moderately to severely active RA who had previously failed TNF inhibitors (ClinicalTrials.gov Identifier NCT02760433/CREDO3) were randomized in a 2:2:1 ratio to receive subcutaneous (SC) injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or placebo (PBO), plus MTX. At week 16, all subjects in the PBO group were randomized in a 1:1 ratio to receive either of OKZ regimes. The primary endpoint was ACR20 response at week 12. Results 368 subjects were randomised according to the protocol and 320 patients (87%) completed the 24-week treatment period. Baseline characteristics were comparable across arms. Both regimens of OKZ were significantly better in primary endpoint: ACR20 were 60.9% (p = 0.0029 in comparison vs. PBO) in OKZ q2w, 59.6% in OKZ q2w (p = 0.0040 in comparison vs. PBO) and 40.6% in PBO. The key efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidences of treatment-emergent adverse events (TEAE) were 65.5% in OKZ q2w, 65.0% in OKZ q4w and 50.7% in PBO. Subsequent randomization of PBO arm at week 16 did not change TEAEs incidence rate per treatment group significantly: 64.3% in any OKZ q2w and 59.7% in any OKZ q4w. The majority of TEAEs in all groups were not serious and were of mild or moderate severity. Incidence of treatment-emergent serious adverse events (TESAE) were: 12 (7.0%) subjects in any OKZ q2w; 6 subjects (3.2%) in any OKZ q4w group, all in the first 16 weeks. The most frequently reported TESAEs across all treatment groups were infections and infestations: 2 (1.2%) in OKZ q2w group, 2 (1.1%) in OKZ q4w group. No opportunistic infections including active tuberculosis, major adverse cardiovascular events, gastrointestinal perforations or deaths were reported. Conclusion In this global Phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs and symptoms of RA compared to PBO plus MTX over a 24-week period. Treatment with OKZ q2w and q4w in this difficult to treat population was well tolerated and consistent with the established safety profile of anti-IL-6 agents. Disclosure E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. M. Luggen: Consultancies; Amgen, Sun Pharmaceuticals, R-Pharm International. Grants/research support; I havAbbvie, R-Pharm, Sun Pharmaceuticals, Pfizer, Novartis, Lilly, and GSK. E. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.