Tumor Necrosis Factor-α Inhibitor Therapy Research Articles

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.

P07 Pityriasis amiantacea: a unique presentation of psoriasis associated with tumour necrosis factor-α inhibitor therapy

Abstract Introduction Pityriasis amiantacea (PA) is a rare but distinctive scalp condition. It is characterised by thick, silvery scales that bind together causing matting of multiple hair shafts. This can ultimately result in temporary or permanent hair loss. PA is thought to be a reaction pattern rather than a specific diagnosis and common associated conditions include: scalp psoriasis, seborrhoeic dermatitis, tinea capitis and atopic dermatitis. We report a case of PA presenting in a patient with longstanding rheumatoid arthritis (RA), associated with tumour necrosis factor-α inhibitor (anti-TNF-α) therapy. Case description A 42-year-old was reviewed at her routine rheumatology follow up appointment. She has a 15-year history of seropositive, erosive RA managed with monthly golimumab injections for the last eight years. Prior to this she had been on etanercept for four years, but this lost efficacy. Unfortunately, she had poor disease control on methotrexate, leflunomide and sulphasalazine. She developed a sore area on her scalp nine months previously with accompanying itch. This then spread into an extensive confluent area of redness, associated with soreness, scale, matting onto hair and hair loss. She had been treated unsuccessfully with multiple antibiotic courses, including flucloxacillin, doxycycline and clarithromycin, oral fexofenadine, topical diprosalic and ketoconazole shampoo. The pruritic skin lesions continued to progress and even spread to behind the ears. This had been managed by her general practitioner (GP) as otitis externa. The patient was otherwise well with no joint pains, fever, weight loss or other systemic features. On examination, thickened, hyperkeratotic scaling plaques were seen with clumped hair shafts and underlying erythema of the entire scalp. There were no skin lesions over the rest of the body and nail changes were absent. Swab culture from the scalp was negative for fungal infection but Staphylococcus aureus and Psuedomonas aeruginosa were identified. Dermatology consult was sought, and she was diagnosed with extensive impetiginized pityriasis amiantacea associated with otitis externa. This was thought to be secondary to her anti-TNF-α therapy. Initial management was with scalp oils to soften the scales, Betnovate scalp ointment and a course of antibiotics. However, the mainstay of treatment was stopping the golimumab. Within one month of these interventions she made a dramatic improvement. Discussion The pathogenesis of PA is yet to be definitively established; however, it has been thought that PA may be a manifestation of an underlying inflammatory skin disease. Most commonly, PA is associated with psoriasis and seborrheic dermatitis. Drug induced cases have also been described. There are case reports of PA occurring in patients treated with valproic acid, vemurafenib and minoxidil. The skin symptoms seen in PA are likely a reaction of hair-bearing scalp to various inflammatory and microbial insults. Moreover, a study undertaken in Egypt found that over 96% of patients with PA had Staphylococcus isolates found in skin swabs taken from the affected scalp. Both S. aureus and S.epidermidis were identified; this could suggest incidental colonisation or that these bacteria play a part in development of PA. Multiple studies have looked at distinguishing microbial biofilms and their structure and physical properties. Resilient biological scaffolding of microbial biofilms, rich in polysaccharides, proteins, lipids, and nucleic acids, is triggered by the bacteria and develops on the scalp and hair shafts. As this continues it promotes accumulation of adherent scale and the hair shafts are increasingly bound together and matted to the scalp. TNF-a is an inflammatory cytokine produced by macrophages during acute inflammation. It causes a range of signalling events within cells, leading to necrosis or apoptosis, which contributes to the pathogenesis of many chronic inflammatory diseases, like psoriasis. However, in some cases TNF-a inhibition can paradoxically lead to new psoriasis or worsening of existing psoriasis. This has been observed with the three major anti-TNF-a agents (infliximab, etanercept and adalimumab). Often it is seen in patients receiving treatment for rheumatoid arthritis or inflammatory bowel disease. On average, cutaneous adverse effects are seen approximately 17 months after starting anti-TNF-a therapy. The most frequently seen presentations are of plaque psoriasis and palmoplantar pustulosis. Key learning points Inhibition of TNF-a causes increased production of interferon-a by dendritic cells, which has been associated with induction of psoriasis. Interleukin-1 (IL-1) has also been implicated in the development of psoriasis. Furthermore, TNF-a can activate apoptosis of potentially autoreactive T-cells. Blockade of this action could lead to T-cell mediated tissue and psoriatic pathology. Anti-TNF-a induced PA is a rare adverse reaction that usually requires drug discontinuation. The exact pathogenetic mechanism is unclear but an imbalance of the cytokine environment has been theorised. Our patient highlights the need to stay vigilant for cutaneous adverse reactions and the evolving diverse spectrum of psoriasiform conditions that can be seen secondary to anti-TNF-a therapy.

Reversing the Inflammatory Process-25 Years of Tumor Necrosis Factor-α Inhibitors.

Immune-mediated inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, peripheral and/or axial spondyloarthritis, Crohn's disease, and ulcerative colitis, are characterized by molecular and cellular changes in the immune system. Due to the systemic nature of these diseases, organs such as the liver or cardiovascular system are often affected by the inflammatory process. Tumor necrosis factor-α inhibitor therapy reduces the activation of pro-inflammatory signaling cascades, mitigates the chronic inflammatory process by restoring cellular balance, and alleviates clinical consequences, such as pain and tissue damage.

Real-world effectiveness of golimumab in adult patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis and an inadequate response to initial TNFi therapy in Greece: the GO-BEYOND prospective, observational study.

The impact of golimumab (GLM) on remission or low disease activity (LDA) was evaluated in patients with moderate-to-severe rheumatoid arthritis (RA), progressive psoriatic arthritis (PsA), or severe axial spondyloarthritis (axSpA), who failed previous treatment for their rheumatic disease with one initial tumor necrosis factor α inhibitor (TNFi). This is a multicenter, prospective, real-world observational 18-month study, conducted in Greece. The primary endpoint, assessed at 6 months, included the proportion of patients attaining LDA and/or remission (Disease Activity Score for 28 joints based on C-reactive protein [DAS28-CRP] ≤ 3.2), minimal disease activity (MDA; MDA criteria), and moderate disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score 4-7), respectively. Other endpoints evaluated the persistence to GLM treatment and its impact on patients' work productivity (Work Productivity and Activity Impairment [WPAI] instrument) and quality of life (QoL; EuroQoL5 dimensions 3 levels [EQ-5D-3L] questionnaire). Descriptive statistics, the Wilcoxon signed-rank test, and Kaplan-Meier method were used for analyses. At 6 months, LDA was achieved by 46.4% of patients with RA, MDA by 57.1% of patients with PsA, and BASDAI 4-7 by 24.1% of patients with axSpA. For all study patients, persistence rates on GLM were high (85.1-93.7%) over 18months; all WPAI domain scores and the EQ-5D-3L index score improved significantly (p < 0.001) from baseline to 18months. GLM treatment was effective in patients with RA, PsA, or axSpA who had failed previous treatment with one TNFi and led to significant WPAI and QoL improvements. Persistence rates were high. Trial registration number and date of registration: As per the local regulations the study has been registered at the national registry for non-interventional studies https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=MK8259-6995 .

Commentary on Cohen et al.: Role of Clinical Factors in Precision Medicine Test to Predict Nonresponse to TNFi Therapies in Rheumatoid Arthritis.

A 2021 study described the development and validation of a blood-based precision medicine test called the molecular signature response classifier (MSRC) that uses 23 features to identify rheumatoid arthritis (RA) patients who are likely nonresponders to tumor necrosis factor-α inhibitor (TNFi) therapy. Both the gene expression features and clinical components (sex, body mass index, patient global assessment, and anti-cyclic citrullinated protein) included in the MSRC were statistically significant contributors to MSRC results. In response to continued inquiries on this topic, we write this letter to provide additional insights into the contribution of clinical components to the MSRC on the Network-004 validation cohort.

Conversion Rate of Tuberculosis Screening Tests among Dermatology Patients Treated with Tumor Necrosis Factor Inhibitors.

Background:The use of tumor necrosis factor-α inhibitors (TNFi) has been associated with an increased risk latent tuberculosis (TB) reactivation. The role of TB screening assays in monitoring patients during TNFi therapy remains uncertain. Spontaneous conversions and reversions have been described.Aims:This study aims to determine the conversion and reversion rate of TB screening tests among dermatology patients receiving TNFi in a country with moderate TB incidence.Subjects and Methods:A retrospective single-center study conducted on all patients in whom treatment with TNFi was initiated in our dermatology clinic in a tertiary university hospital, Riyadh, Saudi Arabia, until September 2018. Data were collected from the hospital electronic patient information system.Results:One hundred and eighteen patients were included. Majority (79.9%) of patients used adalimumab. Psoriasis was the most common indication (90%). Among patients with negative baseline TB screening who had been retested during TNFi therapy (n = 65; 55%), conversion to positive was observed in nine patients (13.8%) with a mean duration of exposure of 39.7 months, whereas among patients with positive TB testing result (n = 18), 10 (55.5%) reverted to negative.Conclusions:This study emphasizes the need for prospective large-scale multispecialty studies assessing the significance of TB retesting, which should be considered when designing rescreening protocols.

Different Effects of Biologics on Systemic Bone Loss Protection in Rheumatoid Arthritis: An Interim Analysis of a Three-Year Longitudinal Cohort Study.

ObjectiveTo compare changes in bone mineral density (BMD) in rheumatoid arthritis (RA) patients receiving three-year conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), tumor necrosis factor-α inhibitors (TNFi), and abatacept.MethodsPatients with RA were recruited from September 2014 to February 2021. Dual-energy X-ray absorptiometry was used to measure BMD at the femoral neck (FN), total hip (TH), and lumbar spine (L1-4) at enrollment and three years later. Changes in the BMD of each regimen group were analyzed. Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict the change in BMD.ResultsA total of 752 participants were enrolled and 485 completed the three-year follow-up period. Of these, 375 (Group I), 84 (Group II), and 26 (Group III) participants received csDMARDs, TNFi, and abatacept therapy, respectively. Considering both type of therapy and completion of the follow-up period, participants were divided into groups A (csDMARDs, n = 104), B (TNFi, n = 52), and C (abatacept, n = 26). Compared to baseline, BMD decreased significantly at FN (p = 0.003) and L1-4 (p = 0.002) in Group A and at L1-4 (p = 0.005) in Group B, but remained stable at all sites in Group C. In terms of regression-adjusted percent change in BMD, there was a significant difference seen at all measured sites between group C compared to both groups A and B (+0.8%, -2.7%, -1.8% at FN; +0.5%, -1.1%, -1.0% at TH; +0.8%, -2.0%, -3.5% at L1-4, respectively; all p < 0.05). Anti-osteoporosis therapy had a BMD-preserving effect in RA.ConclusionCompared with csDMARDs and TNFi, abatacept may have a better BMD-preserving effect in RA. Anti-osteoporosis therapy can prevent systemic bone loss irrespective of RA therapy.

A Molecular Signature Response Classifier to Predict Inadequate Response to Tumor Necrosis Factor-α Inhibitors: The NETWORK-004 Prospective Observational Study.

IntroductionTimely matching of patients to beneficial targeted therapy is an unmet need in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) that predicts which patients with RA are unlikely to respond to tumor necrosis factor-α inhibitor (TNFi) therapy would have wide clinical utility.MethodsThe protein–protein interaction map specific to the rheumatoid arthritis pathophysiology and gene expression data in blood patient samples was used to discover a molecular signature of non-response to TNFi therapy. Inadequate response predictions were validated in blood samples from the CERTAIN cohort and a multicenter blinded prospective observational clinical study (NETWORK-004) among 391 targeted therapy-naïve and 113 TNFi-exposed patient samples. The primary endpoint evaluated the ability of the MSRC to identify patients who inadequately responded to TNFi therapy at 6 months according to ACR50. Additional endpoints evaluated the prediction of inadequate response at 3 and 6 months by ACR70, DAS28-CRP, and CDAI.ResultsThe 23-feature molecular signature considers pathways upstream and downstream of TNFα involvement in RA pathophysiology. Predictive performance was consistent between the CERTAIN cohort and NETWORK-004 study. The NETWORK-004 study met primary and secondary endpoints. A molecular signature of non-response was detected in 45% of targeted therapy-naïve patients. The MSRC had an area under the curve (AUC) of 0.64 and patients were unlikely to adequately respond to TNFi therapy according to ACR50 at 6 months with an odds ratio of 4.1 (95% confidence interval 2.0–8.3, p value 0.0001). Odds ratios (3.4–8.8) were significant (p value < 0.01) for additional endpoints at 3 and 6 months, with AUC values up to 0.74. Among TNFi-exposed patients, the MSRC had an AUC of up to 0.83 and was associated with significant odds ratios of 3.3–26.6 by ACR, DAS28-CRP, and CDAI metrics.ConclusionThe MSRC stratifies patients according to likelihood of inadequate response to TNFi therapy and provides patient-specific data to guide therapy choice in RA for targeted therapy-naïve and TNFi-exposed patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00330-y.

Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial

ObjectiveTo evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment...

Tumour necrosis factor inhibitors in inflammatory bowel disease: the story continues.

In the 1990s, tumour necrosis factor-α inhibitor therapy ushered in the biologic therapy era for inflammatory bowel disease, leading to marked improvements in treatment options and patient outcomes. There are currently four tumour necrosis factor-α inhibitors approved as treatments for ulcerative colitis and/or Crohn’s disease: infliximab, adalimumab, golimumab and certolizumab pegol. Despite the clear benefits of tumour necrosis factor-α inhibitors, a subset of patients with inflammatory bowel disease either do not respond, experience a loss of response after initial clinical improvement or report intolerance to anti-tumour necrosis factor-α therapy. Optimizing outcomes of these agents may be achieved through earlier intervention, the use of therapeutic drug monitoring and thoughtful switching within class. To complement these approaches, evolving predictive biomarkers may help inform and optimize clinical decision making by identifying patients who might potentially benefit from an alternative treatment strategy. This review will focus on the current use of tumour necrosis factor-α inhibitors in inflammatory bowel disease and the application of personalized medicine to improve future outcomes for all patients.

Miliary Histoplasmosis Mimicking Miliary Tuberculosis in a Patient Treated with Tumor Necrosis Factor-α Inhibitor Therapy.

In patients receiving anti–tumor necrosis factor (TNF)-α agents, a miliary pattern on chest imaging is often attributed to tuberculosis. However, fungal infections (histoplasmosis, blastomycosis, and coccidioidomycosis) and metastatic pulmonary disease should also be considered1,2. A 40-year-old woman, diagnosed with ankylosing spondylitis, was in remission with adalimumab. She presented with a 3-week history of fever, night sweats, dyspnea, and dry cough. She reported exposure to demolition dust …

Histoplasmosis in Inflammatory Bowel Disease with Tumor Necrosis Factor-Alpha Inhibitors: Safe to Continue Biologics?

The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections. We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD. We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn's disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically. We identified 49 patients (median age 44years; range 19-76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76ng/mL compared with pulmonary disease alone 0.375ng/mL (p < 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p > 0.05). Median length of stay was 9.5days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7years. Total treatment duration ranged from 3 to 15months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%). Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study

The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P=.001) and resolved HBV (34.3% vs 5.0%, P<.001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. Observational design and a lack of a comparison group. Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Poncet Disease: A Case-based Review of an Uncommon Extrapulmonary Manifestation of Tuberculosis

Background: Tuberculosis (TB), an ancient infectious disease caused by the bacteria Mycobacterium tuberculosis, still remains a leading cause of morbidity and mortality in our modern world, causing ∼1.3 million deaths worldwide in 2017 alone. Because it disproportionately impacts the developing world, the unique manifestations of TB may be less encountered and therefore less known to many physicians in developed countries. Case: A 63-year-old woman, with a past medical history of ulcerative colitis, who was on tumor necrosis factor-α inhibitor therapy, presented with fevers, lymphadenopathy, erythema nodosum, and diffuse joint pains. The differential diagnosis included sarcoidosis manifesting as Lofgren syndrome and TB. A tissue biopsy of her right supraclavicular lymph node confirmed the diagnosis of tuberculous lymphadenitis, reactivated in the setting of her adalimumab therapy. Given the patient’s arthritic symptoms, we were also suspicious for Poncet disease (PD), a lesser-known entity defined by reactive arthritis in the setting of TB. Discussion: This case of an immunocompromised woman with fevers, lymphadenopathy, polyarthritis, and erythema nodosum demonstrates a unique presentation of TB. PD is defined as reactive arthritis due to infection with TB elsewhere in the body. Although PD was first described in 1897, it stills remains a disputed and lesser-known entity. This case highlights the importance of recognizing this unique manifestation of TB to prevent misdiagnosis and delay. It also demonstrates the diagnostic challenge in distinguishing the overlapping features of sarcoidosis manifesting as Lofgren syndrome and PD.

JAAD Game Changers∗: Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: Results from the Italian Psocare Registry

Capsule Summary•Some patients with psoriasis benefit from switching from one anti-tumor necrosis factor-alfa inhibitor to another.•In our series, response to the second anti-tumor necrosis factor-alfa inhibitor was lower in patients who exhibited primary inefficacy to the first anti-tumor necrosis factor-alfa agent than in those who developed drug resistance (secondary inefficacy).•When anticipating a change in therapy, physicians should consider the reason that led to the first drug being discontinued.How did this article change the practice of dermatology?Although each patient's biologic therapy regimen should be tailored individually, consider switching to a biologic medication that works by a different mechanism in cases where a patient experiences treatment failure with primary tumor necrosis factor-α–inhibitor therapy rather than switching to a second tumor necrosis factor-α inhibitor.1

The effect of extra-articular manifestations on tumor necrosis factor-α inhibitor treatment duration in patients with ankylosing spondylitis: nationwide data from the Korean College of Rheumatology BIOlogics (KOBIO) registry.

Tumor necrosis factor-α inhibitor (TNFi) therapy has shown to be remarkably effective for treating ankylosing spondylitis (AS); however, nearly 30% of AS patients every year either stop TNFi therapy or switch to a different TNFi due to inefficacy or adverse effects. The goal of this study was to identify predictors of TNFi treatment duration, including extra-articular manifestations, using a nationwide registry in Korea. Data obtained from the Korean College of Rheumatology Biologics (KOBIO) registry, a nationwide, multi-center database representing 58 tertiary care hospitals in Korea. Demographics, clinical features, laboratory findings, disease activity indices (BASDAI, ASDAS-ESR, ASDAS-CRP), peripheral arthritis, and extra-articular manifestations (uveitis, enthesitis, dactylitis, psoriasis, and inflammatory bowel disease) were studied in patients with AS during TNFi therapy. We also analyzed treatment duration outcomes for five TNFi agents (etanercept, infliximab, infliximab biosimilar, adalimumab, and golimumab), as well as factors associated with treatment duration, particularly in terms of extra-articular manifestations. Univariable and multivariable Cox regression analyses were performed to verify preliminary results. A total 1482 AS patients starting TNFi drug therapy between Dec. 2012 and Jan. 2017 were included. No differences in demographics, disease activity, or extra-articular manifestations were evident between continued and discontinued TNFi groups at baseline, though baseline differences were detected for gender distribution, CRP, platelet counts, and HLA-B27 positivity. During treatment period, the effects of extra-articular manifestations, including uveitis (unadjusted hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.57 to 1.48, p = 0.74), enthesitis, dactylitis, psoriasis, and inflammatory bowel disease, on TNFi treatment duration were not statistically significant. By contrast, the occurrence of peripheral arthritis was significantly associated with shorter TNFi treatment duration (unadjusted HR 2.21, 95% CI 1.66 to 2.95; adjusted HR 1.38, 95% CI 1.01 to 1.88). Among disease activity indices, higher ASDAS-ESR levels were significantly associated with shortening of the TNFi treatment duration (unadjusted HR 1.87, 95% CI 1.73 to 2.03; adjusted HR 2.23, 95% CI 2.00 to 2.63). Among TNFi drugs, golimumab had a lower discontinuation rate than that of etanercept over a 3-year follow-up period (unadjusted HR 0.46, 95% CI 0.31 to 0.68; adjusted HR 0.65, 95% CI 0.43 to 0.99). In a nationwide KOBIO registry, extra-articular manifestations, including uveitis, were not associated with TNFi treatment duration. Among clinical cofactors, the development of peripheral arthritis during TNFi therapy was associated with a higher risk of TNFi treatment discontinuance in AS patients.

The Utility of Screening for Coccidioidomycosis in Recipients of Inhibitors of Tumor Necrosis Factor α.

Tumor necrosis factor α inhibitors (TNFi) are commonly used to treat immune-mediated disorders, but they are associated with an increased risk of mycobacterial and fungal infections. We compared the outcomes of TNFi recipients screened for asymptomatic coccidioidomycosis with those of unscreened patients to compare the development of symptomatic coccidioidomycosis and to describe its outcomes for patients with abnormal coccidioidal screenings. We searched electronic health records from 4 September 2010 through 26 September 2016 for all patients receiving a TNFi for dermatologic, rheumatologic, or gastroenterologic diagnoses, then categorized patients by whether or not they had undergone coccidioidal serologic testing for screening or diagnostic purposes. A total of 2793 patients had a TNFi prescribed. Of those, 1951 met the inclusion criteria: 1025/1951 (52.5%) never had coccidioidal screening; 925/1951 (47.4%) had serologic screening either before beginning TNFi therapy or annually, or both after beginning a TNFi. Symptomatic coccidioidomycosis developed in 35/1025 (3.4%) unscreened patients. Of those screened, 861/925 (93.1%) had negative serologic tests, of which 11/861 (1.3%) subsequently developed symptomatic coccidioidomycosis; 36/925 (3.9%) had coccidioidomycosis at screening (7, probable infection; 11, possible infection; 18, asymptomatic seropositive result); and 17 had only positive findings for immunoglobulin M antibodies and did not meet the definition for coccidioidomycosis. The unscreened cohort was more likely to have symptomatic coccidioidomycosis than the screened cohort (35/1025 vs 11/861, P < .01). Screening for asymptomatic coccidioidomycosis within a Coccidioides-endemic area allowed for identifying and managing asymptomatic coccidioidomycosis before patients began TNFi therapy. Less symptomatic infection developed in the screened than the unscreened cohort.

Mycobacterium Avium Complex Immune Reconstitution Inflammatory Syndrome Associated With Infliximab Use

Abstract Tumor necrosis factor-α inhibitors are a mainstay therapy for patients with moderate to severe Crohn disease. Use of these agents is widely recognized to be associated with an increased risk for tuberculosis as well as fungal and intracellular bacterial infections. However, nontuberculous mycobacterial infections are less well recognized complications of tumor necrosis factor-α inhibitor therapy and can be fatal if undiagnosed. More recently, immune reconstitution inflammatory syndrome has been associated with discontinuation of tumor necrosis factor-α inhibitor therapy. We describe a patient with severe Crohn disease treated with high-dose infliximab therapy who developed disseminated Mycobacterium avium complex and who, after initial improvement with antimycobacterial therapy, subsequently developed an immune reconstitution inflammatory syndrome 13 weeks after her infliximab was discontinued.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Use of Tumor Necrosis Factor-Alpha Inhibitors in Children and Young Adults With Juvenile Idiopathic Arthritis or Rheumatoid Arthritis.

To characterize the use of tumor necrosis factor-α inhibitors (TNFIs) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA). Patients with incident JIA or RA were identified by using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months. TNFI use patterns were examined, including switching among TNFIs, adherence, persistence, and time from diagnosis to TNFI use. Earlier TNFI treatment without prior use of traditional disease-modifying antirheumatic drugs (DMARDs) and use of specific TNFIs were analyzed by age group. Of 6929 children and young adults with new diagnoses of JIA/RA, 18.6% were treated with TNFIs. In these TNFI users, 39.1% received earlier TNFI therapy without prior use of DMARDs. The use of TNFIs was higher in patients diagnosed between 2012 and 2013 than that in patients diagnosed between 2009 and 2011 (hazard ratio 1.13, 95% confidence interval 1.00-1.28). Etanercept was the most commonly used, especially by children aged < 12 (75.5%) and adolescents aged 12 to 17 (62.5%) years. Adherence measured as mean proportion of days covered ranged from 70.4% to 93.2% for individual TNFI agents. Only about 60% of patients continuously took TNFIs for 12 months. When switching occurred, switching from etanercept to adalimumab was the most common pattern. Earlier TNFI therapy was observed in 39.1% of children and young adults taking TNFIs. In addition, the time to the first TNFI prescription became shorter over the study period. Future research should evaluate the long-term effectiveness and safety of this more aggressive TNFI therapy.