Tumor Necrosis Factor Inhibitor Agents Research Articles

Reconstruction of Anterior Chest Wall Defect Induced by Sterile Costochondritis: A Case Report of Non-radiographic Axial Spondyloarthritis

Non-radiographic axial spondyloarthritis (axSpA) is a subtype of axSpA characterized by chronic low back pain and stiffness but without radiographic evidence of sacroiliitis or spinal changes. As is the case with axSpA, early initiation of nonsteroidal anti-inflammatory drugs, tumor necrosis factor inhibitor agents, or physical therapy are often recommended for patients with non-radiographic axSpA. While the clinical course of non-radiographic axSpA is less well-known than axSpA, we present a case of a patient with non-radiographic axSpA manifesting as a sterile abscess in the sternum and costal cartilage. In this case report, we describe the diagnostic process for this rare manifestation and reconstruction of the large chest wall defect using a pedicled transverse rectus abdominis musculocutaneous flap.

Tumor necrosis factor inhibitor (TNFi) persistence and reasons for discontinuation in a predominantly male cohort with axial spondyloarthritis

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12months; 63.5% and 47.1% at 24 and 36months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

Changes in Market Share of Biologic and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs for Treatment of Rheumatoid Arthritis: Results from the Ontario Best-Practice Research Initiative Database.

For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease-modifying anti-rheumatic drugs (cs- DMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for all patients and those initiating their first bDMARD/tsDMARD. All TNFi therapies were included. Non-TNFi included Abatacept, Rituximab, Tocilizumab, and Tofacitinib. A total of 1,057 patients were included, of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/ts- DMARD-naïve patients. In 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. This descriptive analysis of data from the OBRI cohort reveals that TNFi are still used in the majority of cases; however, there has been an increase in the use of non-TNFi therapies both overall and as first-line advanced therapy. This trend towards non-TNFi therapies as first-line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line to any of the advanced therapeutics.

Bone Health in Rheumatoid Arthritis: What Can Studies of Bone Microarchitecture Tell Us?

Introduction: Rheumatoid arthritis (RA) is associated with changes in skeletal health, including increased risk of fracture. This study used a novel technique, high-resolution quantitative CT (HRpQCT), to assess bone microarchitecture in patients with RA. Methods: There were 59 patients (female: 41; male: 18) with RA recruited. They underwent dual energy X-ray absorptiometry and HRpQCT of the radius and tibia. The questionnaire information included age, sex, BMI, disease duration, comorbidities, medication use, smoking and alcohol consumption, rheumatoid factor (RF) or cyclic citrullinated peptide (CCP) status, and disease activity. HRpQCT results were compared with published estimated age and sex-specific values. Results: There were 55 patients (female: 39; male: 16) who had either radial or tibial scans available. The mean age was 55.8 (standard deviation [SD]: 12.6) years and median disease duration was 11.4 years (interquartile range [IQR]: 6.3–19.4). Mean BMI was 27.2 (SD: 5.8). Forty-nine (90.7%) participants were RF or CCP positive, with disease severity ranked as severe in 33 (61.1%) patients and moderate in 20 (37.0%). Fifteen participants (27.8%) had previously taken steroids and 47 (85.5%) were receiving tumour necrosis factor inhibitor (TNF-i) medication. Radial trabecular number and density were lower than expected, and trabecular separation was greater than expected (p<0.05), though tibial results were similar (p<0.10 for trabecular number and separation). No difference in cortical values reached statistical significance in this sample. Previous use of steroids was associated with greater radial periosteal circumference (p<0.05, adjusted for sex) and use of TNF-i agents was associated with lower radial total and trabecular area (p<0.05, adjusted for sex). Conclusion: Trabecular bone microarchitecture differences were observed among patients with RA. Further studies with larger numbers of participants are needed.

Non-TNF inhibitor switchers versus TNF inhibitor cyclers from multicentre rheumatoid arthritis ultrasonography prospective cohort in Japan

To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p < .05). Although there was no significant difference, non-TNFi switchers tended to have a larger decrease than TNFi cyclers in efficacy indicators based on clinical disease activity index and PDUS. Multivariate logistic regression analysis identified a following independent factor associated with both EULAR good response and retention of a biologic agent: non-TNFi switch (p < .05 for both). Non-TNFi switchers were shown to have significantly higher percentage of EULAR good response and higher retention than TNFi cyclers. A non-TNFi biologic agent may hence be a preferential next-line treatment for TNF-IR patients.

Pregnancy in Chronic Arthritis: Only a Matter of Planning

Chronic arthritis often affects women of childbearing age. The old concept that having chronic arthritis constitutes a major obstacle to women when planning a pregnancy is now obsolete. Thanks to our current capacity to control the activity of rheumatoid arthritis and other chronic inflammatory conditions, and due to the availability of highly effective drugs such as tumour necrosis factor inhibitor agents and other biological agents, many women with these diseases are now able to consider the challenge of childbearing and raising children. Careful pre-conceptional evaluation and risk assessment constitutes the first step of proper care, which can be individualised according to the disease. More than ever, rheumatologists must know how to deal with this situation, and must be able to provide adequate counselling regarding the control of arthritis during conception and pregnancy.

Psoriatic arthritis: recent progress in pathophysiology and drug development.

Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy, after rheumatoid arthritis diagnosis, in early arthritis clinics. Most patients have established psoriasis, often for years, prior to the onset of joint pain and swelling; in addition, associated features of nail disease, dactylitis, enthesitis, spondylitis or uveitis may be present. Psoriasis may not be immediately apparent, as small or patchy lesions may occur in the scalp or perineum. PsA presents as a symmetrical polyarthritis, similar to rheumatoid arthritis, or an asymmetrical oligoarthritis with a predilection for the distal interphalangeal joints. Spinal involvement is similar, although not identical, to ankylosing spondylitis. Joint damage occurs early; up to 50% of PsA patients have an 11% annual erosion rate in the first 2 years of disease duration, suggesting it is not a benign condition. There have been significant advances in our understanding of PsA pathogenesis in recent years, in the areas of genetics and molecular biology, implicating both the innate and the adaptive immune systems. This has lead to the introduction of evidence-based targeted therapy, primarily with tumour necrosis factor inhibitor (TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such as methotrexate and leflunomide, remains the first-choice therapeutic intervention, even though there are few randomised controlled trials with these agents. In contrast, a number of successful studies of TNFi agents demonstrate excellent efficacy, in combination with methotrexate, and several novel agents are currently in development for the treatment of PsA.

Ankylosing spondylitis patient responses to TNFi is gender-specific: 6 year data from the distiller biologic registry

ObjectiveTo examine the clinical and serological features of ankylosing spondylitis (AS) patients treated with tumour necrosis factor (TNF) inhibitors (TNFi).MethodsConsecutive, unselected AS patients commencing TNFi were prospectively studied between 2004...

Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis

ObjectivesThis project was undertaken to assess the risk of malignancy in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors (TNFi) in clinical practice, as recorded in prospective, observational...