Use Of Tumor Necrosis Factor Inhibitors Research Articles

Certolizumab pegol-induced immunoglobulin A vasculitis in a patient with rheumatoid arthritis

Abstract Rationale: Certolizumab pegol (CZP) is a tumor necrosis factor (TNF) inhibitor with the unique characteristic of being a humanized Fab′ fragment. Immunoglobulin A (IgA) vasculitis has been reported to be associated with the use of TNF inhibitors, including infliximab, etanercept, and adalimumab. Patient concerns: The case was a 34-year-old Japanese woman with rheumatoid arthritis who had been treated with CZP for 3 years. She had delivered a healthy child 5 months earlier. On presentation, she had a 2-day history of abdominal pain and purpura on the lower extremities. Diagnoses: Histological analyses of a skin specimen revealed inflammatory cell infiltrates around the vessel walls and IgA and C3 deposits in the vessel walls of the upper dermis. Computed tomography showed terminal ileitis. The diagnosis was IgA vasculitis, presumably associated with use of CZP. Intervention: CZP was discontinued and prednisolone was administered. Outcomes: The abdominal pain and purpura promptly improved in response to treatment. No relapse of vasculitis occurred after discontinuation of CZP. Lessons: In this case, the cumulative immunomodulatory effects of the TNF inhibitor and the patient postpartum status were considered to be involved in inducing IgA vasculitis. Clinicians should be aware of IgA vasculitis-related symptoms as a possible adverse effect of TNF inhibitors to ensure prompt diagnosis and appropriate treatment.

Risk factors for herpes zoster in patients with rheumatic diseases: a nationwide cohort study in Korea.

To determine the risk factors for herpes zoster (HZ) in patients with rheumatic diseases in Korea. We used the nationwide database of the Health Insurance Review & Assessment Service to analyse patients aged ≥20 years who had visited a hospital more than twice for rheumatic disease as a principal diagnosis from January 2009 to April 2013. HZ was identified using HZ-related Korean Standard Classification of Diseases 6 (KCD-6) codes and the prescription of antiviral agents. The relationship between demographics, comorbidities and medications and HZ risk was analysed by Cox proportional hazards models. HZ developed in 1869 patients. In Cox proportional hazards models, female sex but not age showed an increased adjusted hazard ratio (HR) for HZ. Comorbidities such as haematologic malignancies, hypertension, diabetes mellitus, and chronic lung and liver diseases led to an increased HR. HZ risk was higher in patients with SLE (HR: 4.29, 95% CI: 3.49, 5.27) and Behçet's syndrome (BS, HR: 4.54; 95% CI: 3.66, 5.64) than with RA. The use of conventional DMARDs, immunosuppressants, TNF inhibitors, glucocorticoids and NSAIDs increased the HR. Infliximab and glucocorticoids (equivalent prednisolone dose >15 mg/day) produced the highest HZ risk (HR: 2.91, 95% CI: 1.72, 4.89; HR: 2.85, 95% CI: 2.15, 3.77, respectively). Female sex, comorbidities and medications increased HZ risk in patients with rheumatic diseases and even young patients could develop HZ. Compared with RA, SLE and BS are stronger HZ risk factors. Patients with rheumatic diseases and these risk factors are potential target populations for HZ vaccination.

Tumor necrosis factor inhibitors prevent structural damage in hips in ankylosing spondylitis-time to reconsider treatment guidelines? A case series and review of literature.

Tumor necrosis factor inhibitors (TNFi) are indicated to treat ankylosing spondylitis (AS), also termed radiographic axial spondyloarthritis (axSpA). The main indication for TNFi is symptom relief, and whether they retard spinal structural damage as assessed by radiography is debated. Hips are the most common "non-spinal" joints involved in AS patients leading to major incapacitation. No major treatment guidelines mention measures to prevent peripheral joint damage, especially hips, in individuals with AS. We present our experience of prevention of structural damage in hips by TNFi in 4 AS patients from our practice. We conducted a literature review looking for articles describing prevention of structural damage progression in hips by TNFi. Over a 10-year period, three out of four patients were treated with TNFi and had no progression in hip damage as assessed by imaging. Only one patient that withdrew the TNFi due to infectious complications developed rapid worsening and required hip arthroplasty. Our literature review showed multiple case series with similar results suggesting that use of TNFi in patients with AS may prevent structural damage and at least postpone a hip replacement at a young age. Based on our experience, as well as from the literature review, we believe that treatment guidelines in axSpA should recommend prompt institution of TNFi following identification of hip involvement in patients to prevent a major source of disability. Whether interleukin (IL)-17 inhibitors or targeted synthetic anti-rheumatic drugs have hip sparing effects in patients with AS should also be investigated. Key Points • Hip involvement in ankylosing spondylitis is a major source of disability. • TNFi prevent hip damage in ankylosing spondylitis. • Prompt institution of TNFi should follow suspicion of hip involvement in ankylosing spondylitis.

The Patterns of Use of Medications for Inflammatory Bowel Disease During Pregnancy in the US and Sweden Are Changing.

Population-level data spanning different countries describing oral and parenteral treatment in pregnant women with inflammatory bowel disease (IBD) are scarce. We studied treatment with sulfasalazine/5-aminosalicylates, corticosteroids, thiopurines/immunomodulators, and tumor necrosis factor (TNF)-inhibitors in the United States (Optum Clinformatics Data Mart and the Medicaid Analytics Extract [MAX]) and in the Swedish national health registers. We identified 2975 pregnant women in Optum (2004-2013), 3219 women in MAX (2001-2013), and 1713 women in Sweden (2006-2015) with a recorded diagnosis of IBD. We assessed patterns of use for each drug class according to filled prescriptions, assessing frequency of treatment continuation in those that were treated in the prepregnancy period. The proportion of women with Crohn's disease and ulcerative colitis on any treatment during pregnancy was 56.1% and 56.3% in Optum, 47.5% and 49.3% in MAX, and 61.3% and 64.7% in Sweden, respectively, and remained stable over time. Sulfasalazine/5-aminosalicylates was the most commonly used treatment in Crohn's disease, ranging from 25.1% in MAX to 31.8% in Optum, and in ulcerative colitis, ranging from 34.9% in MAX to 53.6% in Sweden. From 2006 to 2012, the TNF-inhibitor use increased from 5.0% to 15.5% in Optum, from 3.6% to 8.5% in MAX, and from 0.7% to 8.3% in Sweden. Continuing TNF-inhibitor treatment throughout pregnancy was more common in Optum (55.8%) and in MAX (43.0%) than in Sweden (11.8%). In this population-based study from 2 countries, the proportion of women with IBD treatment in pregnancy remained relatively constant. TNF-inhibitor use increased substantially in both countries.

Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS.MethodsA comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model.ResultsNine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37–0.93, I2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33–0.70, I2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57–1.35, I2 = 76%).ConclusionsIn this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00248-x) contains supplementary material, which is available to authorized users.

Use of TNF Inhibitors in Rheumatoid Arthritis and Implications for the Periodontal Status: For the Benefit of Both?

The inflammatory diseases rheumatoid arthritis (RA) and periodontitis show similarities in misbalances of cytokine levels, such as tumor necrosis factor-α (TNF-α). RA has been treated for two decades with TNF inhibitors which are effective by blocking TNF’s destructive action. Since RA and periodontitis show similarities in high levels of TNF, the periodontal status of RA patients may improve with the use of anti-TNF therapy. To assess this, a systematic review with special emphasis on duration of therapy was performed to evaluate the effect of anti-TNF-α treatment on the periodontal status of RA patients. Overall, studies showed an improvement in periodontal health with anti-TNF therapy. When analyzed over time (6 weeks to 9 months), it became apparent that initial improvements concerned bleeding on probing (BOP) and gingival index (GI) after therapy duration of 6 weeks. Periodontitis parameters that improved after prolonged treatment were: probing pocket depth (PPD) after 3 months and clinical attachment level (CAL) after 6 months. In conclusion, this systematic review reveals that anti-TNF treatment is therefore not only beneficial for rheumatic joints but also for the gums of rheumatoid arthritis patients. We propose that the sequential tissue recovery due to anti-TNF therapy progresses as follows: 1. block of diapedesis by lowering vessel permeability, 2 fewer leukocytes in the inflamed tissue, and 3. reduced proteolytic activity and subsequent repair of collagen fiber functionality and normalization of osteoclast activity. Clinically, this could lead to a decrease in bleeding on probing and ultimately in an improved clinical attachment level.

A RARE COMPLICATION OF TUMOR NECROSIS FACTOR INHIBITORS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Tumor necrosis factor (TNF)-inhibitors are one of the first line agents prescribed for management of rheumatoid arthritis (RA). Hemorrhagic pericardial effusion is a rare side effect of TNF inhibitors1,2, and if left untreated, may cause life threatening complications such as pericardial tamponade or cardiac arrest. CASE PRESENTATION: A thirty-four-year-old morbidly obese female with past medical history of Diabetes and RA presented to the emergency department after a syncopal episode with complains of shortness of breath and anxiety. An emergent Computed tomography scan was done which showed a large pericardial effusion. (Figure 1). As the patient was being transported to intensive care, she developed hypotension and hypoxia leading to cardiac arrest. Cardiopulmonary resuscitation was started. A bedside echocardiogram showed a large circumferential pericardial effusion with tamponade physiology (Figure 2). Return of spontaneous circulation was achieved after six rounds of compressions but the patient remained in obstructive shock requiring multiple vasopressors. An emergent bedside pericardiocentesis was performed and 60cc fluid was drained. She was then taken to the catheterization lab with further drainage of 550cc of hemorrhagic fluid. Post drainage her hypotension resolved and she was weaned off of all vasopressors. Pericardial studies showed an elevated red blood cell with a normal white blood cell count, negative culture and cytology. Autoimmune workup showed elevated histone antibodies. Of note, the patient had a history of seropositive, non-erosive RA which was managed with prednisone and adalimumab. Due to decreased response to adalimumab, patient was switched to etanercept and received her first dose one month prior to presentation which was discontinued after patient developed skin peeling. DISCUSSION: The exact mechanism of TNF-inhibitors causing pericardial tamponade is currently unknown. However, some have proposed a paradoxical flare up of the underlying autoimmune condition, immune-mediated or drug induced reactions as the cause. Even though RA can occasionally cause pericardial effusions, they are not typically hemorrhagic in nature. The significant medication history in our patient along with anti-histone antibodies made drug induced pericardial effusion the likely cause. More research needs to be done to ascertain the pathophysiology of effusions due to TNF-Inhibitors, as with increasing utility of TNF-inhibitors, they may be more common than currently documented. CONCLUSIONS: With increased use of TNF-inhibitors in autoimmune conditions, clinicians should be well aware of their side effect profile as a delayed diagnosis may lead to life threatening complications as was evident in our case. Reference #1: Lather HD, Kahlenberg JM. Hemorrhagic Pericardial Effusion with Tamponade: A Rare Adverse Effect of Infliximab-Case Report and Literature Review. Case reports in rheumatology. 2016;2016:2576496 Reference #2: Soh MC, Hart HH, Corkill M. Pericardial effusions with tamponade and visceral constriction in patients with rheumatoid arthritis on tumour necrosis factor (TNF)-inhibitor therapy. International journal of rheumatic diseases. 2009;12(1):74-77. DISCLOSURES: No relevant relationships by Kourtney Erickson, source=Admin input No relevant relationships by Sara Godil, source=Web Response No relevant relationships by Kareem Godil, source=Web Response No relevant relationships by Emilee Kurtz, source=Web Response

Changes in bone formation regulator biomarkers in early axial spondyloarthritis.

The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. The DEvenir des Spondyloarthropathies Indifférenciées Récentes cohort is a prospective, multicentre French study of 708 patients with early (>3 months-<3 years) inflammatory back pain suggestive of axSpA. Serum levels of BMP-7, sclerostin and DKK-1 were assessed at baseline and after 2 and 5 years. Changes in bone formation regulators over time were analysed using mixed linear models. Serum BMP-7 significantly increased over time, with a median relative change of 223.7% [interquartile range (IQR) 0-10700 (0.17 pg/ml/month), P < 0.001]. Serum sclerostin significantly increased over time, with a median relative change of 14.8% [IQR -7.9-41.4% (0.001 ng/ml/month), P < 0.001]. Serum DKK-1 did not significantly change over time. Serum BMP-7 increased over time in active disease (Ankylosing Spondylitis Disease Activity Score with CRP ≥1.3, P = 0.01), but the increase was less pronounced with TNF inhibitor (TNFi) use (P < 0.001). No determinant was associated with serum sclerostin change. Serum BMP-7 change over 5 years was related with inflammation; it was increased in active disease, but the increase was low with TNFi use. Serum sclerostin levels significantly increased over time, but to a lesser degree than for serum BMP-7. https://clinicaltrials.gov/, NCT01648907.

Pharmacological treatment for managing bone health in axial spondyloarthropathy: systematic review and meta-analysis.

Axial spondyloarthropathy (axSpA) is associated with an increased prevalence of osteoporosis, but no recommendations exist to guide management. This systematic review and meta-analysis aim to assess the efficacy of pharmacological and non-pharmacological interventions on bone mineral density (BMD) in axSpA. Electronic databases were searched from inception to June 2019 for randomised controlled trials (RCTs) and quasi (q)-RCTs with pharmacological and non-pharmacological interventions. Independent reviewers undertook screening, and risk of bias and quality assessments. Primary outcomes of interest were BMD at spine and hip. Eight studies (two RCTs and six qRCTs) were included (602 participants). Moderate level evidence favoured alendronate over placebo at femoral neck [mean difference (MD) 2.01, 95% CI 0.67 to 3.35], but there was low-level evidence showing no effect at the spine. There was moderate level evidence showing no effect of tumour necrosis factor inhibitors (TNFi) on BMD at total hip (MD -0.01, 95% CI -0.06 to 0.04). Very low-level evidence demonstrated no effect of TNFi on spine or femoral neck. Moderate level evidence favoured neridronate over infliximab at the spine (MD 3.26, 95% CI 1.14 to 5.38), but low-level evidence showed no effect at the total hip (MD 2.75, 95% CI -0.21 to 5.71). There were no eligible studies investigating the efficacy of non-pharmacological interventions. We conditionally recommend alendronate for management of low BMD in axSpA. The balance of evidence does not recommend the use of TNF-inhibitors for treating low BMD. There is a lack of high-quality evidence guiding clinicians treating osteoporosis in axSpA.

Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn’s disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

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.

The Use of TNFα Inhibitors in Treating Pediatric Skin Disorders.

Tumor necrosis factor alpha (TNF) inhibitors have had a significant impact in medicine since the approval of the first drug of its class by the US FDA in 1998. New clinical data and indications have emerged for TNF inhibitors in recent years. Currently, four TNF inhibitors have been approved by the US FDA for dermatology, two of which include US FDA-approved pediatric use. In particular, growing evidence supports the use of etanercept and adalimumab as attractive therapies for pediatric psoriasis. Data for use of etanercept in treating toxic epidermal necrolysis and either etanercept or infliximab for Kawasaki disease is expanding. In addition, there have been clinical reports on the use of TNF inhibitors to treat a variety of other pediatric dermatologic conditions. To help clinicians keep pace with the new data provided by many pediatric dermatology studies involving TNF inhibitors, this review provides an overview of the use of TNF inhibitors in the treatment of pediatric plaque psoriasis, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, toxic epidermal necrolysis, and Kawasaki disease. For TNF inhibitors with little data in the pediatric population, data on adult use is discussed. Furthermore, the review summarizes available clinical data on efficacy, safety, and tolerability of agents currently available.

Safety of tumor necrosis factor inhibitor use in patients with concomitant malignancy.

Background/AimsSafety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use.MethodsChart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves.ResultsThirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158). ConclusionsOur findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.

P250 Effect of secukinumab on radiographic progression through 2 years in patients with active PsA: end-of-study results from a Phase 3 study

Abstract Background Secukinumab demonstrated sustained efficacy, inhibition of radiographic progression and a stable safety profile over 52 weeks in patients with psoriatic arthritis (PsA) in FUTURE 5. We report the end-of-study (2-year) results on the effect of secukinumab on radiographic progression in PsA patients in FUTURE 5. Methods Adults (N = 996) with active PsA were randomised to subcutaneous secukinumab 300 mg load, 150 mg load, 150 mg no load or placebo at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter. The secukinumab dose could be escalated from 150 to 300 mg from Week 52 onwards, based on physician judgement. Radiographic progression (mean change in vdH-mTSS) was based on hand/wrist/foot radiographs obtained at baseline, and Weeks 16 (nonresponders), 24, 52 and 104, assessed by two blinded readers (plus an adjudicator if required). Radiographic data were analysed using a linear mixed-effects model (random intercept, random slopes) at Weeks 24 and 52, and as observed at Week 104. Data are presented for patients originally randomised to secukinumab (300 and 150 mg); the 150 mg groups also included patients who had dose escalation to 300 mg. Analyses by prior TNF inhibitor (TNFi) status (naive vs inadequate response) were also performed. Results Overall, 85% (300 mg), 82% (150 mg) and 75% (150 mg no load) of patients completed 2 years of treatment. A total of 86 (39%) and 92 (41%) patients had their dose escalated to 300 mg in the 150 mg and 150 mg no load groups, respectively. In the overall population, the proportions of patients with no radiographic progression (change from baseline in vdH-mTSS≤0.5) with secukinumab were 89.5% (300 mg), 82.3% (150 mg) and 81.1% (150 mg no load) at 2 years; the corresponding proportions of patients with changes from baseline in vdH-mTSS≤0.0 were: 81.2%, 69.1% and 73.4%, respectively. Radiographic progression was low in secukinumab-treated patients in the overall population and by prior TNFi use over 2 years (Table 1). Clinical responses were sustained through 2 years of secukinumab treatment. Conclusion Low radiographic progression was observed over 2 years of treatment with secukinumab 300 and 150 mg in PsA patients. Disclosures H. Tahir: Member of speakers’ bureau; AbbVie, Janssen, Eli Lilly, Novartis. Grants/research support; Novartis, Eli Lilly. P. Mease: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB, Crescendo Bioscience. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer, UCB, Crescendo Bioscience. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB, Crescendo Bioscience. R. Landewé: None. P. Rahman: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis. Grants/research support; Janssen, Novartis. A. Singhal: Grants/research support; AbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt. E. Böttcher: Consultancies; Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis. Member of speakers’ bureau; Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis. S. Navarra: Member of speakers’ bureau; Astellas, Johnson &amp; Johnson, Novartis, Pfizer. A. Readie: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. S. Mpofu: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. E. Delicha: Consultancies; Novartis. L. Pricop: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. D. van der Heijde: Corporate appointments; Imaging Rheumatology BV. Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma.

Is Takayasu arteritis the result of a Mycobacterium tuberculosis infection? The use of TNF inhibitors may be the proof-of-concept to demonstrate that this association is epiphenomenal.

Although the association between Takayasu arteritis (TA) and latent or active Mycobacterium tuberculosis infection has been suggested for a long time, studies conducted in recent years are challenging this notion. Until recently, the possibility of a pathogenic relationship between TA and tuberculosis (TB) was considered a medical curiosity, but the advent of tumor necrosis factor (TNF) inhibitors as therapy for recalcitrant TA cases, as well as the widespread use of Bacille Calmette-Guérin (BCG) for vaccination purposes, has relocated this association as a top priority issue. In an attempt to define whether both diseases are pathogenically linked or if their association is only epiphenomenal in nature, we conduct a thorough literature search on the development of TB in patients with TA receiving TNF inhibitors. From a total of 13 studies that included 214 patients, the occurrence of TB was observed only in two individuals exposed to infliximab. This frequency of 0.93% is similar to that encountered in patients with other rheumatic diseases exposed to TNF inhibitors. Finally, we propose a novel pathogenic model that could reconcile the epidemiological, clinical, and immunological evidence that links TA and TB, while providing rationality for the use of TNF inhibitors in patients with TA.

Personalized medicine in rheumatoid arthritis: How immunogenicity impacts use of TNF inhibitors

Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay - RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n=67), adalimumab (ADL; n=49) or etanercept (ETA; n=47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

Risk of neutropenia in inflammatory bowel disease patients treated with TNF inhibitors: A single-center, retrospective cohort study.

Background/Aim:Tumor necrosis factor inhibitors (TNFi) have become the mainstay of treatment in moderate-to-severe cases of inflammatory bowel disease (IBD). Neutropenia has been reported in patients receiving TNFi for IBD and other diseases. In this study, we aimed to ascertain the relationship between the use of TNFi and the development of neutropenia in patients with IBD.Patients and Methods:This is a retrospective cohort study including all adult patients with IBD receiving TNFi at a tertiary care center over an 11-year period. The primary outcome was the development of any neutropenic episode after starting a TNFi. For our secondary outcomes, we evaluated the impact of concomitant use of 5-aminosalicylic acid (5-ASA) or an immunomodulator on the risk of developing neutropenia.Results:The final analysis included 281 patients. Of those included, 34.2% developed at least one episode of neutropenia while on a TNFi. The majority of these episodes (67.7%) were mild with ANC between 1000 and 1500/mm3. No significant difference was observed in the age, gender, agent used or type of IBD between those who developed neutropenia and those who did not. Concomitant use of azathioprine (OR = 2.32, 95% CI: 1.26–4.28; P = 0.007) or 5-ASA (OR = 3.15, 95% CI: 1.55–6.39; P = 0.001) were significant independent predictors of developing neutropenia.Conclusions:In this study, mild neutropenia was common among patients with IBD on TNFi. Future prospective studies are required to further clarify the significance of neutropenia in patients with IBD receiving TNFi.

Trends in diagnostic prevalence and treatment patterns of male and female ankylosing spondylitis patients in the United States, 2006\u20132016

BackgroundThere has been much variation between epidemiological studies that report the prevalence of ankylosing spondylitis (AS). This study aimed to analyze the diagnostic prevalence rates and treatment patterns of male and female AS patients in the United States adult insured population from 2006 to 2016.MethodsTrends in AS prevalence were calculated for the 11-year period covering January 1, 2006 to December 31, 2016. Adult (18+ years old) AS patients were included in this retrospective analysis of medical and pharmacy claims data from the IBM Marketscan Commercial, Medicaid and Medicare-Supplemental Claims database. Prevalence was determined as having ≥1 AS diagnostic codes (ICD-9:720.0; ICD-10:M45.x). Trends in treatment patterns were also analyzed and stratified by gender.ResultsThe AS prevalence increased from 0.04 to 0.09% from 2006 to 2016. The mean age between 2006 and 2016 ranged from 49.52–50.00 years. In 2006, approximately 40% of AS patients were female, while in 2016 over 47% of AS patients were female. Rates of use of TNF inhibitors and oral glucocorticoids increased, while NSAIDs and non-biologic DMARDs (sulfasalazine & methotrexate) rates decreased. Opioid use rates were stable. In 2016, males were more likely to be prescribed biologics, while females were more likely to be prescribed methotrexate, sulfasalazine, NSAIDs, muscle relaxants, anticonvulsants, opioids, and glucocorticoids.ConclusionsThe prevalence of AS diagnosis codes more than doubled between 2006 and 2016, but the very low prevalence suggests that AS continues to be underdiagnosed and under-addressed in routine clinical practice. Despite the increase in female AS patients, females were less likely to be prescribed biologics compared to male AS patients.

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.