Patients Receiving Tumor Necrosis Factor Research Articles

Protocolo diagnóstico y tratamiento del cuadro febril en el paciente con enfermedad inflamatoria intestinal

Fever is a common clinical manifestation of inflammatory bowel disease (IBD). Nevertheless, fever should not be systematically attributed to inflammation. There are multiple diseases that progress with fever and they may be masked by a flare-up of bowel inflammation. Therefore, a differential diagnosis is recommended. One of the main causes of febrile syndrome is infections. Patients with IBD are at increased risk for infections, in part because of immunosuppressive treatment. In addition, they are more susceptible to certain microorganisms, including enteropathogens such as Clostridioides difficile, and mycobacteria in patients receiving tumor necrosis factor alpha-inhibiting drugs. Second, neoplastic processes, both solid and hematological, can progress with fever, with the disease itself and the use of thiopurines being the main associated risk factors. Other causes of fever that should be considered are inflammatory or autoimmune disorders and drug fever. This protocol proposes an algorithm for the differential diagnosis of febrile illness in patients with IBD.

The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.

Neoehrlichia mikurensis is uncommon in rheumatological patients receiving tumour necrosis factor inhibitors and in blood donors: a retrospective cohort study

IntroductionNeoehrlichia mikurensis is a tick-borne bacterium that primarily causes disease in immunocompromised patients. The bacterium has been detected in ticks throughout Europe, with a 0%–25% prevalence. N. mikurensis infection presents...

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug(bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Incidence of severe infection in patients with rheumatoid arthritis taking biologic agents: a systematic review.

The objective of this review was to estimate the population-based incidence and determine the types of severe infection and deaths experienced by patients with rheumatoid arthritis taking biologic agents. Since the late 1990s, various biologic and synthetic drugs have been developed to treat rheumatoid arthritis. In recent years, the incidence of severe infection in patients with rheumatoid arthritis in Western nations has been determined by observational studies; however, no systematic review has been conducted on this topic. The following inclusion criteria were considered: i) observational studies on patients with rheumatoid arthritis treated with biologic agents; ii) studies reporting the number of severe infections requiring hospitalization for treatment; iii) studies reporting person-years of observation data; and iv) studies based on rheumatoid arthritis registries, medical records from rheumatology centers, or insurance claim databases. PubMed, CINAHL, Embase, and Web of Science were searched to identify published studies. The reference lists of all studies selected for critical appraisal were screened for additional studies. Unpublished studies were searched on MedNar and OpenGrey databases. All the searches were updated on December 6, 2021. After removing the duplicates, 2 independent reviewers screened titles and abstracts against the inclusion criteria and then assessed full texts against the criteria. Two reviewers independently appraised the study and outcome levels for methodological quality using the critical appraisal instrument for cohort studies from JBI. Two reviewers extracted the relevant information related to severe infection and drugs. Fifty-two studies from 21 countries reported severe infection rates associated with using 8 biologic agents, plus nonbiologic disease-modifying antirheumatic drugs. In total, 18,428 infections with 395,065 person-years of biologic drug exposure were included in the analysis. Thirty-five studies included infections in outpatients receiving intravenous antibiotic therapy. Fifteen studies reported the first episode of infection, and the remaining studies did not specify either the first or all of the episodes of infection. Inclusion of viral infection and/or opportunistic infection varied among studies. Fifteen studies reported the site of infection; respiratory, skin/soft tissue, urinary tract, and sepsis/bacteremia were commonly reported. Ten studies reported the case fatality rates, ranging from 2.5% to 22.2%. Meta-analysis was conducted for 8 biologic agents and conventional disease-modifying antirheumatic drugs. The infection rate varied from 0.9 to 18.1/100 person-years. The meta-analysis revealed an infection rate of 5.0/100 person-years (95% CI 3.8-6.7) among patients receiving tumor necrosis factor inhibitors (heterogeneity 98.2%). The meta-analysis for the other 3 biologic agents revealed a point estimate of 5.5 to 8.7/100 person-years with high heterogeneity. Sensitivity analysis indicated that registry-based studies were less likely to have very low or very high infection rates compared with other data sources. The definition of infection, the patient composition of the cohorts, and the type of databases appeared to be the primary sources of clinical and methodological heterogeneity. Due to high statistical heterogeneity, the meta-analysis was not suited to estimating a summary measure of the infection rate. Developing standardized data collection is necessary to compare infection rates across studies. PROSPERO CRD42020175137.

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20-year systematic review and meta-analysis of randomized controlled trials.

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy.

ObjectiveImmunogenicity and safety following receipt of the standard SARS–CoV‐2 vaccination regimen in patients with immune‐mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2‐dose regimen and a third dose of SARS–CoV‐2 vaccine in IMID patients receiving immunosuppressive therapy.MethodsAdult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2‐dose SARS–CoV‐2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor‐binding domain (RBD) of the SARS–CoV‐2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor‐binding domain of the full‐length SARS–Cov‐2 spike protein, were allotted a third vaccine dose.ResultsA total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti‐RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable.ConclusionIMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis.

ObjectiveCell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy.MethodsPeripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF‐α, interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), and interleukin‐17A (IL‐17A) from AS patients were detected at baseline.ResultsBlood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = −0.349, p = 0.001), BASDAI score (r = −0.243, p = 0.020), and ASDASCRP score (r = −0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF‐α (r = −0.237, p = 0.024) and IL‐17A (r = −0.339, p = 0.001) but not with IFN‐γ (p = 0.083) or IL‐10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non‐response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non‐response patients after treatment.ConclusionBlood CDC42 deficiency links with elevated pro‐inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.

The risk factors and incidence of major infectious diseases in patients with ankylosing spondylitis receiving tumor necrosis factor inhibitors

Objectives This study aimed to evaluate the risk factor and incidence of infections in patients receiving tumor necrosis factor inhibitor (TNFi) therapy for ankylosing spondylitis using data from the national health insurance service. Methods This was a retrospective cohort study. Data regarding patients with ankylosing spondylitis prescribed TNFis were obtained from an insurance claims database of the Health Insurance Review & Assessment Service in Korea. Outcomes used were incidence rates of serious infection, pneumonia, tuberculosis, and herpes zoster during the follow-up period as well as the relationship between each TNFi and sex, hazard ratio (HR) of infection-related risk factors, and incidence of infections. Results A total of 2515 patients were included. There were no significant differences among the hazard ratios of TNFis for serious infection, pneumonia, and herpes zoster. However, the hazard ratio of tuberculosis was significantly higher for infliximab than for etanercept (adjusted HR 8.40 [95% confidence interval: 1.06–66.91]). In the subgroup analysis by sex, women treated with golimumab had a significantly higher hazard of herpes zoster than those treated with etanercept (adjusted HR 12.40 [95% confidence interval: 1.40–109.58]). Conclusion We recommend that risk factors for these infectious diseases be identified prior to prescribing TNFis in these patients.

The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial.

The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341). Academic and community-based rheumatology, gastroenterology, and dermatology practices. Adults aged 50 years or older receiving TNFis for any indication. Random assignment to ZVL versus placebo. Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. Potentially limited generalizability to patients receiving other types of immunomodulators. This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

What Is the Risk of Reactivation in Patients with Resolved and Past HBV Infection During Immunosuppressive Therapy If HBV-DNA Negative before Treatment?

Reactivation of Hepatitis B (HBVr) related to immunosuppressive drug therapy (ISDT) in patients with resolved and past infection is a challenging entity. The number of prospective long-term studies is limited. Two groups of patients with resolved and past HBV infection were analyzed prospectively. The patients were further categorized as 266 patients receiving ISDT (group 1) and 246 patients receiving antineoplastic therapy (group 2). We did not detect any cases of HBVr among 108 patients receiving rituximab (71 of which were anti-HBc positive only), 111 patients receiving tumor necrosis factor inhibitors (66 of which were anti-HBc positive only), and 42 patients receiving high-dose glucocorticoids for more than 4 weeks (24 of which were anti-HBc positive only) during a mean follow-up time of more than 24 months. Subgroup analysis of the anti-HBs (+) patients showed that in group A (anti-HBs >1000 mIU/mL) the antibody levels did not change; in group B (anti-HBs between 100 and 1000 mIU/mL) the antibody levels changed non-significantly (P = .25), and in Group C (anti-HBs between 0 and 100 mIU/mL) the antibody levels declined significantly (P = .002). Furthermore, 16 patients in Group C had an anti-HBs loss during follow-up, but no HBVr was detected. The risk of HBVr by immunosuppressive therapy in this group may be lower than that suspected in the literature and anti- HBs levels may not seem to correlate with the risk of reactivation.

Comparison of platelet count and mean platelet volume values before and after treatment in rheumatoid arthritis and ankylosing spondylitis patients receiving tumor necrosis factor alpha inhibitor therapy

Aim: In our study, we planned to reveal the change of the mean platelet volume (MPV) with anti-TNF treatment given in patients with Rheumatoid-Arthritis (RA) and Ankylosing-Spondylitis (AS) and to evaluate the clinical importance of MPV in the follow-up of these diseases.Materials and Methods: Patients who applied to our hospital's between 2011 and 2013 were included in the study. 40 patients participated in the study. The average ages of the patients were 43.8±9.9 years (range:25-68 years). All patients were examined retrospectively, Hemoglobin (Hb), Hematocrit (Hct), Platelet count, Mean Red-Blood-Cell Volume (MCV), MPV, Erythrocyte-Sedimentation-Rate (ESR), C-Reactive Protein (CRP) before anti-TNF treatment were recorded. Then, the same values were checked six months after the treatment. Averages of the Hb, Hct, MCV, PLT, MPV, CRP, ESH parameters of patients before and after treatment were compared with each other.Results: When the values before and after the treatment were compared, there was a significant decrease in ESR (p:0.002). There was also a statistically significant increase in Hb and Hct values after treatment (p:0.002, p:0.039, respectively). A significant decrease was observed in mean platelet count and MPV values after treatment (p:0.001). Although there was an increase in the MCV value, it was not statistically significant. Likewise, there was a decrease in CRP value but it was not statistically significant.Conclusion: In this study, it was concluded that the MPV value and platelet count could be inexpensive biomarkers in the follow-up of RA and AS. However, more controlled prospective studies are needed in this regard.

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.

Unmet needs in ankylosing spondylitis patients receiving tumour necrosis factor inhibitor therapy; results from a large multinational real-world study

BackgroundSymptoms and comorbidities of ankylosing spondylitis (AS) considerably reduce health-related quality of life (HRQoL) and ability to work. This real-world study assessed rates of tumour necrosis factor inhibitor (TNFi) use and switching, treatment failure, and associations between failing TNFi and HRQoL, work productivity and activity impairment (WPAI).MethodsAS patients and their treating physicians completed questionnaires capturing patient demographics, clinical status, TNFi treatment history, reasons for switching TNFi, HRQoL and WPAI. Current TNFi was determined as “failing” if, after ≥3 months, physician-rated disease severity had worsened, remained severe, was “unstable/deteriorating”, physicians were dissatisfied with disease control and/or did not consider treatment a “success”.ResultsThe analysis included 2866 AS patients from 18 countries. Of 2795 patients with complete treatment data, 916 (32.8%) patients had never received TNFi therapy, 1623 (58.1%) patients were receiving their 1st TNFi and 200 (7.2%) patients had ever received ≥2 TNFi (treatment switch). Primary or secondary lack of efficacy were the commonest reasons for switching, and the mean delay in switching after primary lack of efficacy was 11.1 months. 232 (15.4%) patients on TNFi were currently “failing” who, compared to those with treatment success, reported poorer HRQoL: 5-dimension EuroQoL (EQ-5D-3 L): 0.63 vs. 0.78; Medical Outcomes Study Short-Form Health Survey version 2 (SF-36v2) mental component summary (MCS): 41.8 vs. 46.3; physical component summary (PCS): 40.2 vs. 45.1; impaired work productivity: 46.4% vs. 25.0%; and activity: 44.5% vs. 29.6%; all P < 0.001.ConclusionsAmong AS patients, switching TNFi is uncommon and delayed by nearly 1 year despite primary lack of efficacy. Patients currently failing TNFi experience worse physical function, HRQoL and work productivity.

The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors

Introduction To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.

Manage cutaneous adverse effects associated with tumour necrosis factor inhibitors with topical corticosteroids and oral antibiotics

Cutaneous adverse effects (CAEs), such as eczema, psoriasis, and skin infections, are common in patients receiving tumour necrosis factor inhibitors (TNFIs; e.g. adalimumab, etanercept and infliximab). Once a CAE is diagnosed, patients should receive appropriate dermatological care, as this may avoid cessation of TNFI therapy. Topical corticosteroids are the mainstay of therapy for numerous skin lesions, while oral antibiotics are effective in the treatment of superinfections.

P627 Audit of the assessment, prevalence and treatment of osteoporosis in a single-centre cohort of patients with inflammatory bowel disease managed with tumour necrosis factor inhibitor treatment

Despite the high prevalence of osteoporosis in patients with inflammatory bowel disease (IBD), the Australian Inflammatory Bowel Disease Audit 2009 found that only 9% of IBD patients who had received over 3 months of steroid treatment had a bone mineral density (BMD) result recorded in the hospital records in the previous 5 years. We postulated that patients receiving tumour necrosis factor inhibitor (TNFi) therapy would be at the highest risk for osteoporosis. The aims of this audit were: (1) record the number of tertiary hospital IBD clinic patients receiving TNFi therapy who had at least one BMD assessment, (2) to record the prevalence of osteoporosis, (3) to record the number who had a change in management as a result of their BMD assessment. This audit was conducted at a single IBD multidisciplinary referral centre. Inclusion criteria: Crohn’s disease or ulcerative colitis, receiving TNFi treatment. Using an IBD database data extracted included: age, gender, body mass index, ever smoked, BMD scan result, fragility fracture, steroid use, disease activity and change in treatment as a result of BMD assessment. Multivariate analysis using logistic regression compared variables. One hundred and ten patients were identified of whom approximately half were female and the majority had never smoked cigarettes (Table 1). Comparison of 110 patients with inflammatory bowel disease treated with a tumour necrosis factor inhibitor (TNFi). Comparison of 110 patients with inflammatory bowel disease treated with a tumour necrosis factor inhibitor (TNFi). The majority of patients (n = 68, 62%) had a DXA scan of whom a minority had osteopenia (n = 26) or osteoporosis (n = 3). Of patients with a DXA scan, 39 (57%) of patients had received at least 1 course of steroids within the 2 years prior to the scan. Four patients had received steroids without a DXA scan. Of patients with osteoporosis, two had been commenced on intravenous anti-resportive therapy (zoledronic acid). Of the 26 patients with osteopenia, 10 (38%) had a change in management. No fragility fractures were identified in any participant. A period ≥2 years between starting TNFi treatment and DXA scan was associated with a reduced BMD (Table 2). Independent predictors of osteoporosis and osteopenia (T score <−1) in 68 patients with inflammatory bowel disease treated with a tumour necrosis factor inhibitor (TNFi). Independent predictors of osteoporosis and osteopenia (T score <−1) in 68 patients with inflammatory bowel disease treated with a tumour necrosis factor inhibitor (TNFi). In this cohort of moderately severe IBD patients managed at a single centre, compliance with DXA scanning was higher than the national average, but rates could be improved further. Osteopenia was common but established osteoporosis relatively uncommon. The outcomes of anti-resorptive therapy in IBD require a larger cohort with long-term follow-up.

Study of the natural course and specific immunity after herpes zoster in patients with rheumatoid arthritis receiving biologic DMARDs.

Herpes zoster is a common infection especially in elderly persons. It is caused by reactivation of varicella zoster virus (VZV) that has remained dormant within dorsal root ganglia after primary infection. Besides patients with immunodeficiency and malignancies, zoster incidence is also higher in patients with rheumatic diseases compared to the general population. Especially in the group of rheumatoid arthritis (RA) patients being treated with biologics, the risk seems to be steady among regimens with different modes of action (1.6–2.4/100 patients-years). RA patients receiving tumor necrosis factor (TNF) inhibitors are at increased risk during the first year of treatment. The aim of the current research protocol is to evaluate the natural course of herpes zoster and the effect of biologic and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) on the VZV-specific cell mediated immunity in RA patients after herpes zoster infection. We will – prospectively – include RA patients who develop herpes zoster, while being treated with biologics (anti-TNF, tocilizumab, rituximab, abatacept) and a control group comprised of patients with herpes zoster [RA patients under non-biologic therapies (corticosteroids/csDMARDs) and age- and sex-matched healthy controls). Titers of IgG specific antibodies against VZV glycoprotein gp1 and the percentage and absolute number of VZV-specific activated CD4+ T cells (CD4+CD69+IFN-γ+) at the time of rash onset and during follow-up will be measured by ELISA and flow cytometry respectively. This study will contribute to the better understanding of various aspects of immune response to VZV in the modern treatment era with biologic DMARDs.

Efficacy of tumour necrosis factor antagonists in stricturing Crohn’s disease: A tertiary center real-life experience

BackgroundStenosis is the most common complication of Crohn’s disease (CD). Long-term outcome of patients receiving tumour necrosis factor (TNF) antagonists for such disease complication is poorly understood. Methods51 CD patients (from July 2006 to November 2015) who had a diagnosis of small bowel or colonic stenosis, diagnosed by colonoscopy and/or MRI enterography, and were treated with TNF antagonists (adalimumab or infliximab) were enrolled.The primary outcome was to assess the rate of success of TNF antagonists on avoiding abdominal surgery for stricturing CD patients. Results20 patients (39.2%) underwent surgery during the follow-up period. The overall incidence of abdominal surgery was 1.8 per 100 person-months at risk, while the median time to surgery was 37.9 months. The univariable and multivariable Cox’s proportional hazards analysis of baseline parameters indicated that disease location (colonic vs ileal, HR: 28.2, 95% CI: 2.45–324, p=0.007; ileocolonic vs ileal, HR: 3.38, 95% CI: 1.09–10.5, p=0.035), prestenotic dilatation (per 1-mm increase, HR: 1.08, 95% CI: 1.01–1.15, p=0.022) and the existence of non-perianal fistula (HR: 9.77, 95% CI: 2.99–31.9, p<0.001) are independent risk factors for abdominal surgery. ConclusionsIn stricturing CD, anti-TNFs are effective in up to about two-thirds of the patients.

Isoniazid treatment for latent tuberculosis infection is tolerable for rheumatoid arthritis patients receiving tumor necrosis factor inhibitor therapy.

Background/AimsTo evaluate the impact of isoniazid (INH) treatment for latent tuberculosis infection (LTBI) on the development of liver function test (LFT) abnormality and the persistence of tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients.MethodsWe retrospectively enrolled patients with RA who were treated with TNF inhibitors at a university hospital between December 2000 and November 2011. After dividing the patients into two groups based on the occurrence of LFT abnormality during follow-up, we compared demographic and clinical features between the two groups. A multivariable logistic regression analysis was performed to identify the impact of INH treatment on LFT abnormality. The impact of INH treatment on the persistence of TNF inhibitors was also evaluated with the log-rank test and the Cox-proportional hazards model.ResultsA total of 312 RA patients including 96 patients (30.9%) who took INH for LTBI were included in this analysis. Thirty-nine patients (12.5%) experienced LFT abnormalities while using TNF inhibitors. The use of INH was associated with LFT abnormalities (odds ratio, 3.01; 95% confidence interval [CI], 1.39 to 6.48) after adjusting for covariates, including methotrexate use. However, the persistence of TNF inhibitors over 5 years did not differ between patients receiving or not receiving INH treatment (49.4 vs. 54.6%, p = 0.79). INH treatment was not a risk factor for discontinuation of TNF inhibitors (hazard ratio, 1.01; 95% CI, 0.66 to 1.57).ConclusionINH treatment for LTBI in RA patients who started TNF inhibitors is associated with the occurrence of LFT abnormality; however, it does not lead to discontinuation of TNF inhibitors.