TNF-blocker Therapy Research Articles

Familial Mediterranean fever (FMF)-response to TNF-blockers used for treatment of FMF patients with concurrent inflammatory diseases.

Familial Mediterranean fever (FMF) is the most common interleukin 1 (IL-1)-driven monogenic autoinflammatory disease. Yet published data also suggest that tumor necrosis factor (TNF) may have a role in the pathogenesis of FMF and may serve as a target for treatment. In the present study we evaluate this hypothesis. To this goal, we studied the incidental effect on FMF of TNF-directed treatment, administered to colchicine-refractory FMF patients for the management of a concurrent inflammatory disease. The rates of FMF patients and of treatments with complete or nearly complete FMF response were determined, based on the number of FMF attacks during TNF-blocker exposures. The possible effect of various FMF and non-FMF features on the outcome was determined using comparative analysis. Patients were identified and data were retrieved using electronic files from the FMF clinic. Twenty-six patients were identified, each receiving ≥1 of four TNF-blockers for a mean duration of 27.6±16.4months. The TNF-blockers were found to induce complete or nearly complete FMF response in 10 (38.5%) of the patients, and in 13 of 50 (26%) exposures. No clinical, genetic, demographic, or therapeutic feature could predict which FMF patient would respond favorably to TNF-blocker therapy. This study suggests that TNF-blockers may be beneficial for a small proportion of colchicine-resistant FMF patients.

C3 AND C4 COMPLEMENT – BIOMARKERS FOR PROGNOSIS OF TREATMENT OF TNF-BLOKERS

Introduction: The complement system adds antibodies and helps phagocytic cells to destroy pathogens from the body. This is part of a congenital immune system that is not adaptive and does not change over the individual life. However, complement can be "triggered" by the adaptive immune system. The complement system is the main effector of the humoral patr of the immune system. Activation of complement results in opsonization, chemotaxis and cytolysis. Regulation of the complement system can control inflammatory diseases including psoriatic arthritis and vice versa, complement fixation disorders can lead to illness. Treatment with anti-TNF blokers complement activity in patients with inflammatory joint diseases.Objective: To investigate C3, C4 fractions of complement, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement the response prediction and monitoring of anti-TNF treatment in patients with psoriatic arthritis.Materials and Methods: 36 patients were included sequentially before treatment with TNF-a-blokers. C3, C4, ESR, CRP were assessed at baseline at 6 and 12 months after initiation of treatment with TNF-α blockers. The activity of the disease is measured by the DARSA disease activity scale, the responses being compared with a control group of persons similar in gender and age. Statistical data processing was performed using the SPSS v25.Results and conclusions: According to the results obtained, C3 and C4 were significantly higher than controls at initiation of treatment (C3 111.3 ± 30.8, C4 91.9 ± 12.4 mg / dl, controls 19.1 ± 8.3 mg / dl, 10.2 ± 5.6 mg / dl p = 0.001, p = 0.001). At 6 and 12 months of follow-up, 76.2% of patients had a reduction in the level of C3 and C4 (p = 0.002, 0.001, respectively). It was found that higher baseline levels of C3 were associated with higher DARSA values at 6 and 12 months.Conclusion: The study of the C3 and C4 complement fractions can be used as biomarkers to estimate the prognosis of TNF-blocker therapy.

Central nervous system involvement in rheumatoid arthritis: possible role of chronic inflammation and tnf blocker therapy.

Rheumatoid arthritis (RA) is a chronic disease, the etiology of which has yet to be clarified, which causes activation of proinflammatory pathways that bring about joint and systemic inflammation. Although peripheral nervous system anomalies are observed widely in RA, very few case reports on changes in the central nervous system (CNS) have been published. In recent years, the pathophysiology of CNS involvement that can occur in RA has attracted a great deal of attention. Emphasis has focused on the possibility that CNS involvement occurs due to blood-brain barrier (BBB) damage associated with chronic inflammation. The present study was performed to investigate the possible effects of BBB dysfunction and tumor necrosis factor (TNF) blocker therapy on BBB function, which may cause CNS damage in patients with RA. 58 RA patients [47 (81.0%) females, 11 (19.0%) males] and 34 healthy controls [24 (70.6%) females, 10 (29.4%) males] were included in the study. All RA patients were on synthetic DMARD therapy at the beginning. Thirty patients continued DMARD therapy, and 28 patients with high disease activity were started on TNF blocker therapy. All demographic characteristics of the patients were recorded. Disease activity was evaluated using the Disease Activity Score 28-joint count C reactive protein. The Mini-Mental State Examination was used to evaluate cognitive function, and the Fazekas scale was used to assess cranial lesions visualized by magnetic resonance imaging (MRI). Patients' peripheral blood S100β, glial fibrillary acidic protein (GFAP), claudin, interleukin (IL)-17, and IL-1β levels were measured at the beginning of the study and after 6months. Demographic characteristics (including sex, age, and body mass index) were similar in the RA and control groups. S100β and GFAP levels were significantly higher in the patient group than in the control group. In the group that was started on TNF blocker therapy, S100β and GFAP levels were significantly decreased 6months after commencement of treatment. No difference was observed between the RA and control groups in terms of hyperintense lesions seen on cranial MRI. The S100β levels increased with lesions in the deep white matter seen on cranial MRI in patients with RA. In conclusion, next to decreasing disease activity and joint erosions by suppressing inflammation, anti-TNF therapy in RA can also suppress potential CNS involvement linked to BBB (blood-brain barrier) dysfunction. Further studies with broader participation and longer patient follow-up are needed to reinforce this hypothesis.

SP0126 How to Treat (HOT) Spondyloarthritis?

Spondyloarthritis (SpA) can be split into axial (ax) and peripheral SpA, according to the predominant clinical presentation. Major progresses have been made over the last decade defining optimal treatment for...

FRI0149 Dikkopf-1 (DKK-1) Serum Levels in Axial Spndyloarthritis (AXSPA) Are Related to Disease Duration

BackgroundTumor necrosis factor (TNF) alpha is responsible for induction of dkk-1 which down-regulates bone formation. Therefore, it was expected that TNF-blocker therapy would inhibit radiographic progression in patients with axSpA...

THU0178 Rates of Serious Infections and Malignancies among Rheumatoid Arthritis Patients Receiving Either Tnf-Blocker or Rituximab Therapy in Finland

BackgroundWhile randomized clinical trials have not showed an increased risk for serious infections among TNF-blocker users in comparison to methotrexate, we sought to confirm the results in Finnish routine care...

THU0276 Importance of TNFAIP3 Gene Polymorphism for RA Susceptibility and Prediction of Therapy Outcome of Tnf-Blocker Therapy

BackgroundTNFα inducible protein 3 (TNFAIP3) belongs to a group of genes that were found to be differentially regulated in PBMC of anti-TNFα treated patients with rheumatoid arthritis (RA) with different...

Treatment Patterns Following Discontinuation of Adalimumab, Etanercept, and Infliximab in a US Managed Care Sample

Because clinical guidelines do not offer clear recommendations for treatment options after discontinuing a tumor necrosis factor (TNF) blocker, this study evaluated treatment patterns within 360 days after discontinuation of TNF-blocker treatment. The IMS LifeLink Health Plan Claims database was used to identify patients diagnosed with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received etanercept, adalimumab, or infliximab between January 1, 2005 and March 31, 2009. Discontinuation from index (first) TNF blocker was defined as switching to a different TNF blocker or a >45-day gap in therapy. Patients were categorized into mutually exclusive groups in descending order: (a) restart of index TNF blocker; (b) switch to another TNF blocker; (c) switch to a different biologic; (d) switch to nonbiologic therapy; or (e) no new treatment. Among 27,704 patients who initiated TNF-blocker therapy, 14,707 (53%) patients discontinued treatment over 1-3 years of follow-up. Within 360 days of discontinuing index TNF blocker, 53.4% of patients restarted index therapy: etanercept 59.9%, adalimumab 46.5%, and infliximab 43.1% (P < 0.001 for etanercept vs. adalimumab and infliximab). The majority of therapy restarts occurred within the first 3 months after discontinuation. Other patients switched to another TNF blocker: etanercept 17.1%, adalimumab 19.1% (P = 0.010 vs. etanercept), and infliximab 15.0% (P = 0.009 vs. etanercept). Switches from index TNF blocker to non-TNF-blocker biologic therapy were low: etanercept 1.9%, adalimumab 4.1%, and infliximab 10.7% (P < 0.001 for etanercept vs. adalimumab and infliximab). Switches from index TNF blocker to nonbiologic treatments were 5.4% for etanercept, 6.5% for adalimumab, and 6.9% for infliximab. Restarting of index TNF-blocker therapy occurs frequently after discontinuation, suggesting that long gaps in TNF-blocker therapy may be common. A significantly higher proportion of etanercept patients restarted their index TNF blocker within 3 months of discontinuation, compared with adalimumab and infliximab patients.

National and regional dose escalation and cost of tumor necrosis factor blocker therapy in biologic-naïve rheumatoid arthritis patients in US health plans

Objective:This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy.Methods:This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005–2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose > recommended label dose, (2) average ending dispensed dose > maintenance dose, and (3) average dose after maintenance dose > maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees.Results:Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p < 0.0001), average ending dispensed dose (1.1% vs 10.6% adalimumab and 63.0% infliximab; p < 0.0001), and average dose after maintenance dose methods (2.8% vs 15.7% adalimumab and 69.6% infliximab; p < 0.0001). Regional dose escalation rates and magnitudes of escalation were directionally consistent with national rates. Etanercept had the lowest cost per treated RA patient ($19,690) compared to adalimumab ($23,020) and infliximab ($24,030).Limitations:Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ∼50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations.Conclusions:In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.

Treatment Challenges in Axial Spondylarthritis and Future Directions

Major progress has been made in recent years in the management of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Most predictors of response have been defined for TNF-blocker therapy, and new treatment strategies are being discussed about how to best reach remission and how to maintain remission. Other biologics besides TNF-blockers have been tested in AS but have so far failed. The IL-17/IL-23 cytokines currently seem to be the most interesting targets. Short-term TNF-blocker therapy does not inhibit radiographic progression but long-term might do so. NSAIDs have been proven to inhibit such progression, even after 2 years of treatment. The effect of a combined therapy of NSAIDs with TNF-blockers on the inhibition of new bone formation in AS patients is currently unknown.

AB0499 Post-discontinuation treatment patterns for tumor necrosis factor-blockers in rheumatoid arthritis patients in the US

BackgroundEtanercept (ETN), adalimumab (ADA), and infliximab (INF) are the 3 most frequently prescribed tumor necrosis factor (TNF)-blocker therapies that are approved by the US Food & Drug Administration for treatment...

SAT0021 Both Gray-Scale Synovial Hypertrophy and Synovial Power Doppler Signals on a Comprehensive Ultrasound Scan are the Predictive Factors of Relapse After Discontinuation of Biological Agents in Patients with Rheumatoid Arthritis

BackgroundClinical information does not accurately predict relapse after discontinuation of biological agents in patients with rheumatoid arthritis (RA). Although ultrasound is a sensitive tool to detect sub-clinical synovial inflammation in...

SAT0143 Tumor necrosis factor-blocker use in us managed care: Utilization and dosing patterns among rheumatoid arthritis patients

BackgroundThe 3 most common tumor necrosis factor (TNF)-blocker therapies for the treatment of moderate to severe rheumatoid arthritis (RA) are etanercept (ETN), adalimumab (ADA), and infliximab (INF). Treatment patterns (discontinuation,...

AB0495 Functional outcome in response to treatment with dmards compared to anti-TNF agents in a cohort with rheumatoid arthritis

BackgroundPatient focussed therapy in rheumatoid arthritis should meet the needs of the patients. From the perspective of the patient with rheumatoid arthritis control of symptoms and the prevention of disability...

OP0027 A single nucleotide polymorphism in the MED29 gene is associated with the clinical outcome of a TNF-blocker and B-cell directed therapy in RA patients

BackgroundDue to the wide range of highly specific and effective biologicals for the treatment of RA it has become of great importance to identify biomarkers for the prediction of therapy...

AB0847 Comparison of treatment responses to TNF-blockers in axial spondyloarthritis patients with short vs long symptom duration

ObjectivesTo investigate the influence of disease duration on treatment response and on the correlation between improvement of patients’ symptoms and improvement in objective measures of inflammation in patients with axial...

Psoriasis treatment patterns with etanercept and adalimumab in a United States health plan population

Background: A retrospective study utilizing administrative claims from a US commercial health plan was performed to examine etanercept and adalimumab treatment patterns among patients with psoriasis (PSO). Methods: Biologic-naïve PSO patients initiating etanercept or adalimumab therapy between 18 January 2008 and 31 December 2008 were identified. Patients continuously enrolled in the health plan for 6 months before and ≥12 months after therapy initiation were followed until disenrollment from the plan or 31 December 2009. Persistence was defined as continuous use of index TNF blocker without a gap in therapy ≥60 days. Patients with gaps in index therapy ≥60 days were classified as discontinuing, switching, or restarting the index therapy. Results: In total, 497 patients initiated etanercept and 330 the adalimumab therapy. Mean age for both groups was 43 years. Approximately 40–42% of patients were persistent on their index TNF blocker for 1 year. Among patients with a ≥60-day gap in therapy, discontinuation without restart or switch occurred in 37% of etanercept and 45% of adalimumab patients (p = 0.04). Differences in therapy restart or switching between the groups were not statistically significant. Conclusions:TNF-blocker therapy persistence is low among PSO patients in this health plan. More than one-third of patients restarted their index TNF blocker after a gap in therapy.

Dose escalation of TNF-blocker therapy among patients with psoriasis in a large managed care plan

Dose escalation of TNF-blocker therapy among patients with psoriasis in a large managed care plan

Dose escalation of TNF-blocker therapy among US managed care patients with psoriasis

Dose escalation of TNF-blocker therapy among US managed care patients with psoriasis

Synovial lymphoid neogenesis is associated with IL-23 expression and disease activity in rheumatoid arthritis

Methods ST samples were obtained by arthroscopy from the inflamed knee of 62 RA patients. A second biopsy was obtained after a mean of 8±5 months of treatment in 21 patients who started TNF blockers. ST samples were immunostained with CD3 (T cell), CD20 (B cell), and MECA-79 (high endothelial vessels). Total ST mRNA was extracted and gene expression of CCR7, LT-beta, IL-7, IL10, IL-17A, IL-21, IL-22, IL-23, TNF-alpha, IL-1b, and IL6 was measured by quantitative real-time PCR. Clinical and biological data were collected at inclusion and after a median follow-up of 2.3 years. Results 28 out of 62 patients (45.2%) had LN, which was associated with a significantly-higher expression of three key molecular markers of LN: CCR7, IL-7 and LT-beta (p<0.037, p<0.038, and p=0.009, respectively). LN-positive patients also had higher IL-23 (p=0.035) and higher DAS28 score, both at inclusion and at the end of followup (p=0.055 and p=0.037, respectively). In the group of patients with ST before and after TNF blocker therapy, EULAR good response was associated with IL-10 reduction (p=0.035). In the entire group, EULAR response correlated with IL-1b expression (P=0.014). Conclusion RA patients with LN were characterized by higher expression of key molecular markers of LN, IL-23 and higher disease activity. A significant reduction in IL-10 expression after therapy with TNF-blockers was associated with good EULAR response.