Initiation Of Tumor Necrosis Factor Inhibitors Research Articles

Analysis of the shorter drug survival times for Janus kinase inhibitors and interleukin-17 inhibitors compared with tumor necrosis factor inhibitors in a real-world cohort of axial spondyloarthritis patients - a retrospective analysis from the RHADAR network

In recent years Janus kinase inhibitors (JAKi) have joined tumor necrosis factor inhibitors (TNFi) and interleukin (IL)-17 inhibitors (IL-17i) as approved disease modifying anti-rheumatic drugs (DMARD) for moderate to severe forms of axial spondyloarthritis (axSpA). Drug survival in axSpA patients has not been well studied in a real-world outpatient scenario since the approval of JAKi. We aimed to analyze the three drug classes based on modes of actions (MoA) for their persistence rates among German axSpA outpatients. A retrospective analysis of the RHADAR database for axSpA patients with a new initiation of TNFi, IL-17i, or JAKi treatment between January 2015 and October 2023 was conducted. Analyses included Kaplan-Meier curves and adjusted Cox regressions for drug discontinuation. 1222 new biological DMARD (TNFi [n = 954], IL-17i [n = 190]) or JAKi (n = 78) treatments were reported. The median drug survival was 31 months for TNFi, 25 for IL-17i, and 18 for JAKi. The corresponding 2-year drug survival rate was 79.6%, 72.6%, and 62.8% for TNFi, IL-17i, and JAKi, respectively. The probability for discontinuation for JAKi was significantly higher compared with TNFi (HR 1.91 [95% CI 1.22–2.99]) as well as for IL-17i compared with TNFi (HR 1.43 [95% CI 1.02–2.01]), possibly related to more frequent use of TNFis as first-line therapy. IL-17i and JAKi discontinuation probabilities were similar. Primary non-response was the reason for drug discontinuation in most cases across all MoA. TNFi treatment might persist longer than JAKi and IL-17i in German axSpA outpatients, possibly related to more severe or refractory disease in patients with JAKi-treated or IL-17i-treated axSpA.

Risk of Venous Thromboembolism With Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk-Enriched Rheumatoid Arthritis Patients.

The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.

Real-World Treatment and Care Patterns in Patients With Rheumatoid Arthritis Initiating First-Line Tumor Necrosis Factor Inhibitor Therapy in the United States.

Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real-world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first-line tumor necrosis factor inhibitor (TNFi). Data from adult patients with RA initiating a first-line TNFi were collected from the American Rheumatology Network (January 2014-August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. Among TNFi initiators (n=15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n=1,651), 52% discontinued their initial TNFi during follow-up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non-TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. In clinical practice, over half of patients with RA initiating a first-line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA.

Insurance Status and Tumor Necrosis Factor Inhibitor Initiation Among Children With Juvenile Idiopathic Arthritis in the CARRA Registry.

Prompt escalation to tumor necrosis factor inhibitors (TNFis) is recommended for children with juvenile idiopathic arthritis (JIA) and ongoing disease activity despite treatment with conventional disease-modifying antirheumatic drugs (cDMARDs). It is unknown whether these recommendations are equitably followed for children with different insurance types. We assessed the association of insurance coverage on the odds and timing of TNFi use. We conducted a retrospective study of children with newly diagnosed JIA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We compared the odds of starting a TNFi in the first year and time from cDMARD to TNFi initiation between those with public and private insurance. We identified 1086 children with new JIA diagnoses. Publicly insured children had significantly higher active joint counts and parent/patient global assessment scores at the enrollment visit. They were also more likely to have polyarticular arthritis compared to those with private insurance. Odds of any TNFi use in the first year did not differ between publicly and privately insured children. Publicly insured children were escalated from cDMARD to TNFi more quickly than privately insured children. Children who were publicly insured had more severe disease and polyarticular involvement at registry enrollment compared to those who were privately insured. Whereas overall TNFi use did not differ between children with different insurance types, publicly insured children were escalated more quickly, consistent with their increased disease severity. Further research is needed to determine why insurance coverage type is associated with disease severity, including how other socioeconomic factors affect presentation to care.

Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis

The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28 < 2.6). This study included 109 RA patients, including 97 (89%) women and 30 (27.5%) with erosions, who were treated with a TNFi. Higher baseline DAS28 was negatively associated with achievement of remission (OR = 0.56, 95% CI 0.35–0.88). The TNFi retention rate was significantly lower in RA patients with than in those without erosions (p = 0.04). Factors significantly associated with drug discontinuation included the presence of erosions (HR = 2.45, 95% CI 1.08–5.51) and higher time-averaged DAS28 (HR = 2.17, 95% CI 1.47–3.20), whereas concomitant methotrexate was associated with lack of drug discontinuation (HR = 0.40, 95% CI 0.17–0.95). The presence of erosions and high time-averaged disease activity could predict poor retention of TNFi by RA patients. Higher baseline DAS28 was associated with a reduced clinical response in patients with RA.Trial registration Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.

Determinants of Tumor Necrosis Factor Inhibitor Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomess.

ObjectiveThe objectives of this study were to characterize the reasons for tumor necrosis factor inhibitor (TNFi) initiation in patients with juvenile spondyloarthropathy (JSpA) and identify clinical correlates and to assess the effect of TNFi therapy on JSpA disease activity.MethodsWe conducted a retrospective cohort study of 86 patients with JSpA with first‐time use of a TNFi over a 7‐year period at Stanford Children's Health. We assessed the physician's reason for TNFi initiation, disease activity at 6 months, and clinical disease status at 12 months following TNFi start. Changes in active joint count, enthesitis count, and pain were measured. Demographics, physician reasons for TNFi initiation, and clinical characteristics were summarized.ResultsThe mean age at JSpA diagnosis was 12.4 years (SD 4.0 years), and the mean time from diagnosis to TNFi initiation was 1.6 years (SD 2.3 years). The most common reason for initiating a TNFi was active disease on physical examination (61%). At 6 months post TNFi initiation, patients on average had three fewer active joints and one fewer active enthesitis point. Patient‐reported pain improved from moderate/severe to mild. After 12 months, 54% of patients had active disease.ConclusionThe physician's decision to initiate a TNFi relied mostly on physical examination findings. Despite improvement in arthritis, enthesitis, and patient‐reported pain at 6 months post TNFi initiation, the majority of the patients still had active disease after 1 year of therapy.

POS0027 SECULAR TRENDS IN BASELINE CHARACTERISTICS, TREATMENT RETENTION AND RESPONSE RATES IN 27189 BIO-NAÏVE AXIAL SPONDYLOARTHRITIS PATIENTS INITIATING TNFI – RESULTS FROM THE EUROSPA COLLABORATION

Background:Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bio-naïve axial spondyloarthritis (axSpA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in axSpA patients initiating a first TNFi.Methods:Prospectively collected data on bio-naïve axSpA patients starting TNFi in routine care from 15 European countries were pooled. According to year of TNFi initiation, three groups were defined a priori based on bDMARD availability: Group A (1999–2008), Group B (2009–2014) and Group C (2015–2018). Retention rates (Kaplan-Meier), crude and LUNDEX adjusted1 remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) &lt;1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) &lt;20) and response (ASDAS Major and Clinically Important Improvement (MI/CII), BASDAI 50) rates were assessed at 6, 12 and 24 months. No statistical comparisons were made.Results:In total, 27189 axSpA patients were included (5945, 11255 and 9989 in groups A, B and C).At baseline, patients in group A were older, had longer disease duration and a larger proportion of male and HLA-B27 positive patients compared to B and C, whereas disease activity was similar across groups.Retention rates at 6, 12 and 24 months were highest in group A (88%/81%/71%) but differed little between B (84%/74%/64%) and C (85%/76%/67%).In all groups, median ASDAS and BASDAI had decreased markedly at 6 months (Table 1). The ASDAS values at 12 and 24 months and BASDAI at 24 months were higher in group A compared with groups B and C. Similarly, crude remission and response rates were lowest in group A. After adjustments for drug retention (LUNDEX), remission and response rates showed less pronounced between-group differences regarding ASDAS measures and no relevant differences regarding BASDAI measures.Conclusion:Nowadays, axSpA patients initiating TNFi are younger with shorter disease duration and more frequently female and HLA-B27 negative than previously, while baseline disease activity is unchanged. Drug retention rates have decreased, whereas crude remission and response rates have increased. This may indicate expanded indication but also a stable disease activity threshold for TNFi initiation over time, an increased focus on targeting disease remission and more available treatment options.

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India

Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Impact of tumor necrosis factor inhibitors and methotrexate on diabetes mellitus among patients with inflammatory arthritis

BackgroundTo determine whether initiation of a tumor necrosis factor inhibitor (TNFi) or methotrexate improves hemoglobin A1c in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) who also have diabetes mellitus (DM).MethodsA retrospective cohort study was conducted in Optum’s de-identified Clinformatics® Data Mart Database, an administrative claims database, using data from 2000 to 2014. Patients with PsA, RA, or AS, with DM (defined by ICD-9-CM codes) and/or HbA1c ≥7%, who newly initiated either a TNFi, MTX, or metformin (positive control) were identified. The change in HbA1c after drug initiation was calculated. Statistical differences in the change in HbA1c between drugs were assessed using the Wilcoxon rank sum test and linear regression models adjusting for potential confounders.ResultsAmong 10,389 drug initiations in 9541 patients with PsA, RA, or AS, and available HbA1c values, HbA1c was ≥7 at baseline in 254 (35%) TNFi initiations, 361(37%) MTX initiations, and 2144 (50%) metformin initiations. Median HbA1c change was − 0.35 (IQR -1.10, 0.30) after TNFi initiation, − 0.40 (IQR -1.20, 0.30) after MTX initiation, and − 0.80 (IQR -1.60, − 0.10) after metformin initiation. In adjusted analyses, TNFi initiators had less of a decrease in HbA1c compared to MTX initiators (β 0.22, 95% CI: 0.004, 0.43), p = 0.046. Metformin initiators had a significantly greater decrease in HbA1c than MTX, β − 0.38 (95% CI: − 0.52, − 0.23), p < 0.001. Glucocorticoid use was not accounted for in the models.ConclusionHbA1c decreased with TNFi initiation or MTX initiation. Reductions in HbA1c after initiation of a TNFi or MTX are about half (~ 0.4 units) the decrease observed after initiation of metformin.

Changes in Opioid Utilization Following Tumor Necrosis Factor Inhibitor Initiation in Patients with Rheumatoid Arthritis.

IntroductionPain control is one of the most important aspects of rheumatoid arthritis (RA) management from the patient’s perspective. Newer generations of RA treatment including tumor necrosis factor inhibitor (TNFi) have the potential to alleviate pain and thus reduce opioid utilization. However, patterns of opioid utilization before and after TNFi initiation have not been well characterized. This study aims to examine multiple measures of change in opioid utilization after the initiation of TNFi.MethodsPatients aged ≥ 18 years with RA and 24 months continuous enrollment between January 2007 and December 2015 who newly initiated a TNFi in IQVIA™ Health Plan Claims Data were included in our study. Opioid utilization at baseline and during follow-up were identified and compared.ResultsOf 2330 patients with RA that were included in the study, 38.8% of patients used opioids in both baseline and follow-up periods. From pre-index to post-index, the proportion of patients receiving any opioid decreased from 54.0 to 51.0%. In addition, the proportion of those who received ≥ 50 mg median daily MED decreased from 12.6 to 10.6% during pre-post periods.ConclusionsThis real-world study of commercially insured patients with RA suggests that opioid use among these patients is prevalent. There was a small decrease in overall opioid utilization after TNFi initiation.

Association of Ustekinumab vs TNF Inhibitor Therapy With Risk of Atrial Fibrillation and Cardiovascular Events in Patients With Psoriasis or Psoriatic Arthritis

Accumulating evidence indicates that there is an increased risk of cardiovascular disease among patients with psoriatic disease. Although an emerging concern that the risk of atrial fibrillation (AF) may also be higher in this patient population adds to the growing support of initiating early interventions to control systemic inflammation, evidence on the comparative cardiovascular safety of current biologic treatments remains limited. To evaluate the risk of AF and major adverse cardiovascular events (MACE) associated with use of ustekinumab vs tumor necrosis factor inhibitors (TNFi) in patients with psoriasis or psoriatic arthritis. This cohort study included data from a nationwide sample of 78 162 commercially insured patients in 2 US commercial insurance databases (Optum and MarketScan) from September 25, 2009, through September 30, 2015. Patients were included if they were 18 years or older, had psoriasis or psoriatic arthritis, and initiated ustekinumab or a TNFi therapy. Exclusion criteria included history of AF or receipt of antiarrhythmic or anticoagulant therapy during the baseline period. Initiation of ustekinumab vs TNFi therapy. Incident AF and MACE, including myocardial infarction, stroke, or coronary revascularization. A total of 60 028 patients with psoriasis or psoriatic arthritis (9071 ustekinumab initiators and 50 957 TNFi initiators) were included in the analyses. The mean (SD) age was 46 (13) years in Optum and 47 (13) in MarketScan, and 29 495 (49.1%) were male. Overall crude incidence rates (reported per 1000 person-years) for AF were 5.0 (95% CI, 3.8-6.5) for ustekinumab initiators and 4.7 (95% CI, 4.2-5.2) for TNFi initiators, and for MACE were 6.2 (95% CI, 4.9-7.8) for ustekinumab initiators and 6.1 (95% CI, 5.5-6.7) for TNFi initiators. The combined adjusted hazard ratio for incident AF among ustekinumab initiators was 1.08 (95% CI, 0.76-1.54) and for MACE among ustekinumab initiators was 1.10 (95% CI, 0.80-1.52) compared with TNFi initiators. No substantially different risk of incident AF or MACE after initiation of ustekinumab vs TNFi was observed in this study. This information may be helpful when weighing the risks and benefits of various systemic treatment strategies for psoriatic disease.

The usefulness of routine chest radiograph examinations in patients treated with TNF inhibitors for inflammatory arthritis in South Korea.

We aimed to investigate the usefulness of routine chest radiograph (CXR) examinations for patients with inflammatory arthritis treated with a tumor necrosis factor (TNF) inhibitor in terms of (i) the role of CXR in baseline latent tuberculosis infection (LTBI) screening and (ii) detecting asymptomatic active tuberculosis after TNF inhibitor initiation. From January 2011 to June 2017, 469 patients with inflammatory arthritis were enrolled in the study at a tertiary referral center in South Korea. At our institution, CXR was performed for all patients undergoing a tuberculin skin test (TST) and/or an interferon-gamma release assay (IGRA) at the LTBI screening visit. LTBI treatment was determined by (i) positive TST or IGRA or (ii) CXR findings suggestive of spontaneously healed tuberculosis. After TNF inhibitor initiation, patients were recommended to undergo CXR at a specified interval. Of 469 patients, 187 were treated for LTBI. Among them, 181 patients were treated for LTBI because of a positive TST or IGRA result. TST was considered positive if induration size was ≥10 mm. The remaining six patients were considered positive on the basis of CXR findings compatible with spontaneously healed tuberculosis, such as noncalcified nodules with distinct margins and fibrotic linear opacity, despite demonstrating negative results for TST and IGRA. Thus, CXR had a diagnostic value as a baseline LTBI test in 6 (1.3%) patients. After TNF inhibitor initiation, 2 patients who had respiratory symptoms were diagnosed with active tuberculosis. For asymptomatic patients, routine CXR follow-up could not detect any case of active pulmonary tuberculosis within 1 year (n = 219) or after 1 year (n = 217). CXR should be performed as one of the LTBI screening tests for patients with inflammatory arthritis in a tuberculosis-prevalent country. However, after TNF inhibitor treatment, routine CXR follow-up was not advantageous.

Preventive effect of tumor necrosis factor inhibitors versus nonsteroidal anti-inflammatory drugs on uveitis in patients with ankylosing spondylitis.

To compare the preventive effect of tumor necrosis factor (TNF) inhibitors (anti-TNF antibody and soluble TNF receptor fusion protein (TNFR)) and nonsteroidal anti-inflammatory drugs (NSAIDs) on uveitis in patients with ankylosing spondylitis (AS). This retrospective cohort study included all AS patients (n = 1055) who have been treated with either TNF inhibitor or NSAIDs at the Seoul National University Hospital from 2004 to 2016. Treatment episodes of each patient were assigned to anti-TNF antibody (n = 517), TNFR (n = 341), and NSAID (n = 704) groups. The incidence of uveitis in each group was compared using a Cox proportional hazard model. The incidence rates of uveitis before and after initiation of TNF inhibitors were also assessed. A propensity score-matched (PSM) comparison was performed for a sensitivity analysis. Uveitis was significantly less common in the anti-TNF antibody group than the NSAID group (adjusted hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.29-0.96) while it was higher in the TNFR group (adjusted HR 2.25, 95% CI 1.43-3.53). Anti-TNF antibody further reduced the incidence of uveitis when prescribed with NSAIDs (combination therapy) (adjusted HR 0.39; 95% CI 0.19-0.79). Combination therapy was preventive in AS patients with a history of uveitis (adjusted HR 0.31; 95% CI 0.12-0.81), but not in those without history of uveitis. The incidence rate of uveitis fell from 6.36 to 2.60 per 100 person-years when anti-TNF antibody was added to NSAIDs. Anti-TNF antibody plus NSAIDs reduces the risk of uveitis to a greater extent than NSAIDs alone in AS patients with a history of uveitis. Combination therapy may be an effective secondary prevention measure.

Comparison of latent tuberculosis infection screening strategies before tumor necrosis factor inhibitor treatment in inflammatory arthritis: IGRA-alone versus combination of TST and IGRA.

This study aims to compare the latent tuberculosis infection (LTBI) screening strategy of interferon-gamma release assay (IGRA)-alone and in combination with tuberculin skin tests (TSTs) before the initiation of tumor necrosis factor (TNF) inhibitor treatment in patients with inflammatory arthritis. Between January 2011 and June 2017, we enrolled 476 patients who were followed up for ≥1 year after the TNF inhibitor initiation in a tertiary referral center in South Korea. Inflammatory arthritis comprised rheumatoid arthritis in 266 (55.9%) and ankylosing spondylitis in 210 (44.1%) patients. The following strategies were used for LTBI screening during the study period: (i) from January 2011 to October 2014, the combination of TST and QuantiFERON-TB Gold In-Tube (QFT-GIT); (ii) between November 2014 and February 2015, QFT-GIT-alone and (iii) since March 2015, either the combination of TST and QFT-GIT or QFT-GIT-alone depending on the attending physician's choice. We compared the screening strategies of QFT-GIT alone and in combination with TST. Overall, 338 (71.0%) patients received LTBI screening tests using the combination of TST and QFT-GIT, and 138 (29.0%) received QFT-GIT-alone. In addition, the LTBI tests were positive in 159 (47.0%) of 338 patients using the combination tests, and 43.8% (148/338) required LTBI treatment. Meanwhile, the LTBI tests were positive in 32.6% (45/138) of QFT-GIT-alone patients, and 30.4% (42/138) required LTBI treatment. Among 338 patients who received combination tests, 2 patients developed active tuberculosis within 1 year after the TNF inhibitor initiation. Of patients who received QFT-GIT-alone, no patient developed tuberculosis. In conclusion, among patients who received QFT-GIT-alone, the number of patients who required LTBI treatment declined compared to the TST and QFT-GIT combination, and none developed active tuberculosis within 1 year, suggesting that QFT-GIT-alone could be a potential screening strategy for diagnosing LTBI in patients with inflammatory arthritis in South Korea.

Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are associated with inflammation. We tried to investigate the influence of tumor necrosis factor inhibitors (TNFi) and tocilizumab (TCZ) on the glucose metabolism of RA patients. RA patients in whom treatment with TNFi or TCZ was initiated from 2008 to 2015 were studied based on their medical records. We analyzed patients whose glycosylated hemoglobin (HbA1c) levels were measured both before and 3 months after the initiation of these biologic agents. The association between HbA1c reduction and the treatment was evaluated. From 971 cases treated with these biologic agents, 221 cases whose medical records of HbA1c were available, were included (TNFi, n = 154; TCZ, n = 67). Both the TNFi and TCZ groups had significantly lower HbA1c values at 1 month and 3 months after the initiation of treatment (TNFi, p<0.001; TCZ, p<0.001). Although the pretreatment HbA1c values did not differ (TNFi, 6.2%; TCZ, 6.2%; p = 0.532), the 3-month treatment HbA1c values were lower (TNFi, 6.1%; TCZ, 5.8%; p = 0.010) and the changes in HbA1c (ΔHbA1c) were greater (TNFi, 0.1%; TCZ, 0.4%; p<0.001) in the TCZ group. The reduction of HbA1c—defined by the achievement of a ΔHbA1c of ≥0.5%—was associated with baseline diagnosis of diabetes mellitus, baseline diabetes treatment, hospitalization, medical change during the observation period, and TCZ. In the multivariate logistic regression analysis, TCZ was associated with the reduction of HbA1c in comparison to TNFi (adjusted OR = 5.59, 95% CI = 2.56–12.2; p<0.001). The HbA1c levels in RA patients were significantly lower after the initiation of TNFi or TCZ. Our study suggests that TCZ decreases the HbA1c levels in RA patients to a greater extent than TNFi.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis.

AIMTo determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study.METHODSPatients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi’s, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs (DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTSTwo thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events (-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events (+5.85 mg/dL, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events (-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β = -0.58, P = 0.01) and hydroxychloroquine (β = -5.78, P = 0.01) use as predictors of lower post-medication-initiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure (β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSIONNo statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis.

ObjectiveRheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients.MethodsIn 171 RA patients we investigated the following SNPs: rs7574865 (STAT4), rs2233945 (PSORS1C1), rs7234029 (PTPN2) and rs33980500 (TRAF3IP2). Remission, LDA, and EULAR response were registered at 6 months and 2 years after initiation of first line TNF-i [Adalimumab (ADA) and Etanercept (ETN)].ResultsSTAT4 variant allele was associated with the absence of a good/moderate EULAR response at 2 years of treatment in the whole RA group and in ETN treated patients. The PTPN2 SNP was associated with no good/moderate EULAR response at 6 months in ADA treated patients. Patients carrying PSORS1C1 variant allele did not reach LDA at 6 months in both the whole RA group and ETN treated patients. TRAF3IP2 variant allele was associated with the lack of LDA and remission achievement at 6 months in all RA cohort while an association with no EULAR response at 2 years of treatment occurred only in ETN treated patients.ConclusionsFor the first time, we reported that SNPs in STAT4, PTPN2, PSORS1C1, and TRAF3IP2 are associated with response to TNF-i treatment in RA patients; however, these findings should be validated in a larger population.

Usefulness and limitations of QuantiFERON-TB Gold in Japanese rheumatoid arthritis patients: proposal to decrease the lower cutoff level for assessing latent tuberculosis infection

We aimed to determine the sensitivity and specificity of QuantiFERON-TB Gold (QFT-G) in Japanese rheumatoid arthritis (RA) patients with a past history of tuberculosis (TB). We assessed whether it is possible to decrease the cutoff using receiver operating characteristic (ROC) analysis. We evaluated chest computed tomography (CT) findings, prior history of treatment, and contact with active TB in 370 RA patients. Forty-nine patients before initiation of treatment with tumor necrosis factor (TNF) inhibitors were divided into two groups: 22 with a past history of TB and 27 without. We estimated the efficacy of QFT-G compared with the tuberculin skin test and antituberculosis (anti-TB) glycolipid antigen antibody. QFT-G was positive (≥0.35 IU/ml) in 13.6% with a past history of TB, increasing to 27.3% at the intermediate range cutoff of 0.1 IU/ml. The sensitivity and specificity of QFT-G was 0.27 and 1.00, respectively, at 0.1 IU/ml. Using ROC analysis, the area under the curve (AUC) of QFT-G but not for the other two tests was significantly large. QFT-G is a useful diagnostic method due to its superior specificity, but the use of a cutoff value of 0.35 IU/ml will likely result in an underestimate. We propose that a lower interferon-γ (IFN-γ) titer of 0.1 IU/ml be adopted when deciding to administer anti-TB drugs before initiation of TNF inhibitors.

Usefulness and limitations of QuantiFERON-TB Gold in Japanese rheumatoid arthritis patients: proposal to decrease the lower cutoff level for assessing latent tuberculosis infection

We aimed to determine the sensitivity and specificity of QuantiFERON-TB Gold (QFT-G) in Japanese rheumatoid arthritis (RA) patients with a past history of tuberculosis (TB). We assessed whether it is possible to decrease the cutoff using receiver operating characteristic (ROC) analysis. We evaluated chest computed tomography (CT) findings, prior history of treatment, and contact with active TB in 370 RA patients. Forty-nine patients before initiation of treatment with tumor necrosis factor (TNF) inhibitors were divided into two groups: 22 with a past history of TB and 27 without. We estimated the efficacy of QFT-G compared with the tuberculin skin test and antituberculosis (anti-TB) glycolipid antigen antibody. QFT-G was positive (>or=0.35 IU/ml) in 13.6% with a past history of TB, increasing to 27.3% at the intermediate range cutoff of 0.1 IU/ml. The sensitivity and specificity of QFT-G was 0.27 and 1.00, respectively, at 0.1 IU/ml. Using ROC analysis, the area under the curve (AUC) of QFT-G but not for the other two tests was significantly large. QFT-G is a useful diagnostic method due to its superior specificity, but the use of a cutoff value of 0.35 IU/ml will likely result in an underestimate. We propose that a lower interferon-gamma (IFN-gamma) titer of 0.1 IU/ml be adopted when deciding to administer anti-TB drugs before initiation of TNF inhibitors.