Effectiveness Of anti-TNF Agents Research Articles

Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis

MHC class I polypeptide-related sequence A (MICA) is a stress-induced protein involved in activation of NK and T cells through interaction with NKG2D receptor. These molecules are atypically expressed in synovium of patients diagnosed with rheumatoid arthritis (RA). A total of 279 patients with RA, qualified to TNF-blockade therapy, were genotyped for MICA rs1051792 SNP. The effectiveness of anti-TNF agents was assessed with European League Against Rheumatism criteria. Significant relationship between MICA rs1051792 and outcome of TNF-blockade therapy has been found. The MICA rs1051792 GG genotype was overrepresented in patients non-responsive to anti-TNF drugs in comparison with other genotypes (p = 0.010). On the other hand, beneficial therapeutic response was more frequently detected among RA subjects possessing heterozygous genotype than those with homozygous genotypes (p = 0.003). Furthermore, increased MICA concentrations in serum were observed in patients possessing MICA rs1051792 GG genotype as compared with those with GA or AA genotypes (p = 1.8 × 10−5). The results from this study indicate the potential influence of MICA rs1051792 polymorphism on modulation of therapeutic response to TNF-blockade treatment in RA.

Cost-savings of adalimumab in hidradenitis suppurativa: a retrospective analysis of a real-world cohort.

The introduction of adalimumab in the management of hidradenitis suppurativa (HS) raises questions regarding the cost-efficacy of treatment. To explore cost-efficacy of treatment with anti-tumour necrosis factor (TNF) agents in a real-world cohort. Patients with Hurley stage II and III HS with ≥1year of follow-up and at least three visits per year from September 2003 to December 2016 were analysed. Patient visits were divided into two categories - visits for treatment with agents blocking TNF or visits for other therapies. The cost of exacerbations was calculated based on the cost of items provided in current price lists or by the national health insurance agency in cases of hospitalization. Effectiveness of anti-TNF agents was calculated by assessing containment of exacerbations. The primary study end point was the cost-savings achieved using anti-TNF agents. Overall, 1211 patient visits for 250 patients were analysed. Total containment of exacerbations was found in 25·1% of visits involving other therapies and in 63·4% of visits involving anti-TNF agents. The cost-savings per patient visit for patients receiving anti-TNF agents vs. other therapies was €178·92. The odds ratio for the total containment of exacerbations among patients with Hurley stage II and III was 4·86 and 6·03, respectively (P=0·466). Treatment with anti-TNF agents was an independent variable affecting annual cost as shown by two-way analysis of variance. In Hurley stage III HS, mean annual cost was €8309·60 under other therapies compared with €3264·20 using anti-TNF agents (P=0·004). Treatment with anti-TNF agents achieves significant cost-benefit through containment of HS exacerbations. The efficacy of anti-TNF agents was similar for both disease stages.

MP19-13 UNCERTAIN IMPACT OF ANTI-TNF AGENTS ON MALE FERTILITY: ARE MEN BEING COUNSELED?

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II1 Apr 2018MP19-13 UNCERTAIN IMPACT OF ANTI-TNF AGENTS ON MALE FERTILITY: ARE MEN BEING COUNSELED? Lauren F. Cooley, Isaac Lam, James Wren, Nelson Bennett, and Robert Brannigan Lauren F. CooleyLauren F. Cooley More articles by this author , Isaac LamIsaac Lam More articles by this author , James WrenJames Wren More articles by this author , Nelson BennettNelson Bennett More articles by this author , and Robert BranniganRobert Brannigan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.662AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adult men with autoimmune conditions are commonly prescribed anti-TNF agents. Literature on the effect of anti-TNF agents on male fertility is sparse, under-powered and with mixed results; but, some studies have reported adverse effects on semen parameters and sperm quality. Given this lack of clear evidence, our objective was to see if men receiving anti-TNF agents are being (1) counseled regarding potential adverse reproductive effects, (2) screened for anatomic or laboratory abnormalities associated with infertility and (3) offered sperm cryopreservation. METHODS A single-center, retrospective analysis of 1012 male patients prescribed an anti-TNF agent between ages 18-45 from 1/1/2008 to 8/1/2017. Our retrospective database review determined if men received (1) counseling regarding risk to fertility, (2) a genitourinary exam (penis, urethra, testicles), (3) screening for varicocele, (4) diagnosis or assessment for low libido or ED, (5) testosterone level, (6) semen analysis, (7) sperm cryopreservation. Chi square test compared proportions between those who did and did not receive counseling. p<0.05=significant. RESULTS Of 1012 men started on anti-TNF agents, only 10.2% received counseling regarding the potential adverse effect of these agents on fertility. Age was not a statistically significant factor related to likelihood to receive counseling (p=0.77). Those who received counseling were significantly more likely to have a genitourinary exam performed, be assessed for presence of a varicocele, be asked about or endorse low libido or ED, have a testosterone level checked, and have a semen analysis performed before or during treatment (all, p<0.0001). There was no statistical difference found between rates of sperm cryopreservation between those who did or did not receive counseling (p=0.7923) and overall rates of cryopreservation were low: 3.4% (no counseling) and 3.9% (counseling). CONCLUSIONS The impact of anti-TNF agents on male fertility is unknown. Our study is the first to demonstrate the lack of patient education regarding the potential for adverse reproductive effects with only 10.2% of men receiving counseling. Those who were counseled were more likely to be screened for anatomic, hormonal, and semen analysis parameters that could impact fertility. Lastly, sperm cryopreservation was rarely offered suggesting prescribing physicians may be unaware of this option for patients. Until a prospective trial is performed to better understand the impact of anti-TNF agents on male fertility, men should be counseled about the possible risk and fertility preservation. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e249 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Lauren F. Cooley More articles by this author Isaac Lam More articles by this author James Wren More articles by this author Nelson Bennett More articles by this author Robert Brannigan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

P362. Agalactosyl IgG predicts therapeutic effect of anti-TNF agents in patients with Crohn's Disease

P362. Agalactosyl IgG predicts therapeutic effect of anti-TNF agents in patients with Crohn's Disease

Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

AB0390 Serum RANKL Activity is Suppressed by TNF Alpha Inhibition but not with MTX Alone

BackgroundBone is, together with cartilage a central target of rheumatoid arthritis (RA). Chronic synovitis attacks the juxtaarticular bone, where it causes bone erosions. Formation of bone erosions is a consequence...

A Sonographic Lesion Index for Crohn's Disease Helps Monitor Changes in Transmural Bowel Damage During Therapy

Therapeutic antibodies against tumor necrosis factor α (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but little is known about the effects of anti-TNF agents on structural damage in the intestine. Small-intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD [SLIC]) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index scores less than 150. We observed significant improvements in SLIC scores and subscores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and subscores and index classes were improved significantly in patients with vs without clinical responses. Controls had no improvements in terms of CD activity index or SLIC scores, or index classes. Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD.

Sa1110 Comparing the Effectiveness of Anti-TNF Agents for the Treatment of Crohn's Disease: a Bayesian Network Meta-Analysis

Sa1110 Comparing the Effectiveness of Anti-TNF Agents for the Treatment of Crohn's Disease: a Bayesian Network Meta-Analysis

AB0534 Efficacy and safety to use halfdose abatacept therapy between 24weeks in patients with rheumatoid arthritis in japanese

BackgroundIn recent years, biological agents are widely used for the treatment of rheumatoid arthritis (RA) and there are several registries for the treatment of RA in other countries. However, in...

951 Effectiveness of Anti-TNF Agents in the Treatment of Entero-Urinary Fistulas in Crohn's Disease

951 Effectiveness of Anti-TNF Agents in the Treatment of Entero-Urinary Fistulas in Crohn's Disease

P531 Effectiveness of anti-TNF agents in the treatment of entero-urinary fistulas in Crohn's disease

P531 Effectiveness of anti-TNF agents in the treatment of entero-urinary fistulas in Crohn's disease

Comparative Effectiveness of Anti-TNF Agents for Crohn’s Disease in a Tertiary Referral IBD Practice

The three Food and Drug Administration (FDA)-approved anti-tumor necrosis factor drugs (anti-TNFs) for Crohn's disease (CD) have not been directly compared. To compare the efficacy of the three anti-TNFs for CD in clinical practice. Retrospective review of patients initiated on anti-TNF between 2004 and 2008. Disease activity, quality of life, and remission rates were compared between groups over 1 year. Sixty patients with CD were initiated on anti-TNF from 2004 to 2008: 31 on infliximab (IFX) and 29 on adalimumab (ADA) or certolizumab pegol (CTZ). More patients in the ADA/CTZ scores group had prior exposure to anti-TNF (76 versus 10%, p < 0.01). Mean Harvey-Bradshaw Index (HBI) scores in the IFX group were lower than in the ADA/CTZ group at 12 months (2.72 ± 3.34 versus 5.63 ± 5.33, p = 0.03). At 12 months, more IFX patients were in remission compared with those on ADA/CTZ (88 versus 53%, p ≤ 0.01). Mean short inflammatory bowel disease questionnaire (SIBDQ) scores were not different between the IFX and ADA/CTZ groups at 12 months. Stratified analyses and logistic regression based on prior anti-TNF use did not show differences in remission rates at any time point post-baseline between groups. After adjustment for prior anti-TNF there was no difference in remission rates between the IFX and ADA/CTZ groups at any time point post-baseline. This suggests that differences between groups were accounted for by a higher rate of prior anti-TNF in the ADA/CTZ group. Our results should be reviewed with caution given the small sample size.

Tu1876 The Effects of Anti-TNF Agents on the Expansion of T Helper-Type 17 (TH17) Cells Driven by Lipopolysaccharide-Stimulated Monocytes

Tu1876 The Effects of Anti-TNF Agents on the Expansion of T Helper-Type 17 (TH17) Cells Driven by Lipopolysaccharide-Stimulated Monocytes

Golimumab for the treatment of psoriatic arthritis

This paper presents a summary of the evidence review group (ERG) report into the use of golimumab for the treatment of psoriatic arthritis (PsA). The main clinical effectiveness data were derived from a single phase III randomised controlled trial (RCT: GO-REVEAL) that compared golimumab with placebo for treating patients with active and progressive PsA who were symptomatic despite the use of previous disease-modifying antirheumatic drugs or non-steroidal anti-inflammatory drugs. The 14-week data showed that, compared with placebo, golimumab 50 mg significantly improved joint disease response as measured by American College of Rheumatology (ACR) 20 [relative risk (RR) 5.73, 95% confidence interval (CI) 3.24 to 10.56] and Psoriatic Arthritis Response Criteria (PsARC) (RR 3.45, 95% CI 2.49 to 4.87), and skin disease response as measured by the Psoriasis Area and Severity Index (PASI) 75 (RR 15.95, 95% CI 4.62 to 59.11). The 24-week absolute data showed that these treatment benefits were maintained. There was a significant improvement in patients' functional status as measured by the Health Assessment Questionnaire (HAQ) change from baseline at 24 weeks (-0.33, p < 0.001). The open-label extension data showed that these beneficial effects were also maintained at 52 and 104 weeks. However, PASI 50 and PASI 90 at 14 weeks, and all of the PASI outcomes at 24 weeks, were not performed on the basis of intention-to-treat analysis. Furthermore, analyses of the 24-week data were less robust, failing to adjust for treatment contamination due to patient crossover at week 16. The manufacturer conducted a mixed treatment comparison (MTC) analysis. The ERG considered the assumption of exchangeability between the trials for the purpose of the MTC analysis to be acceptable, and the statistical approach in the MTC analysis to be reliable. Regarding the safety evaluation of golimumab, the manufacturer failed to provide longer-term data or to consider adverse event data of golimumab from controlled studies in other conditions, such as rheumatoid arthritis and ankylosing spondylitis. Although the adverse effect profile of golimumab appears similar to other anti-tumour necrosis factor (TNF) agents, the longer-term safety profile of golimumab remains uncertain. The manufacturer's submission presented a decision model to compare etanercept, infliximab, golimumab and adalimumab versus palliative care for patients with PsA. In the base-case model, 73% of the cohort of patients were assumed to have significant psoriasis (> 3% of body surface area). Estimates of the effectiveness of anti-TNF agents in terms of PsARC, HAQ change and PASI change were obtained from an MTC analysis of RCT data. The manufacturer failed to calculate incremental cost-effectiveness ratios (ICERs) correctly by comparing golimumab with palliative care instead of the most cost-effective alternative (etanercept). Despite the manufacturer's claim that golimumab is a cost-effective treatment option, the manufacturer's own model showed that golimumab is not cost-effective compared with other biologics when the ICERs are correctly calculated. None of the sensitivity analyses carried out by the manufacturer or the ERG regarding uncertainty in the estimates of clinical effectiveness, the acquisition and administration cost of drugs, the cost of treating psoriasis and the utility functions estimated to generate health outcomes changed this conclusion. However, a key area in determining the cost-effectiveness of anti-TNF agents is whether they should be treated as a class. If all anti-TNF agents are considered equally effective then etanercept, adalimumab and golimumab have very nearly equal costs and equal quality-adjusted life-years (QALYs), and all have an ICER of about £ 15,000 per QALY versus palliative care, whereas infliximab with a higher acquisition cost is dominated by the other biologics.

Disseminated granuloma annulare: A cutaneous adverse effect of anti-TNF agents

Tumor necrosis factor-alpha (TNF-α) inhibitors, such as etanercept, infliximab, and adalimumab, bind to TNF-α and thereby act as anti-inflammatory agents. This group of drugs has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, moderate to severe plaque psoriasis, ankylosing spodylitis, Crohn disease, and juvenile idiopathic arthritis. We describe a 56-year-old woman who developed an erythematous pruritic rash on both arms—diagnosed as granuloma annulare by skin biopsy—approximately 22 months after initiating adalimumab for treatment of rheumatoid arthritis. On stopping adalimumab there was total clearance of the skin lesions, but a similar rash developed again when her treatment was switched to another anti-TNF agent (etanercept). This clinical observation supports a link between TNF inhibition and the development of granuloma annulare.

Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: results from the Dutch Rheumatoid Arthritis Monitoring register

Experience with anti-TNF agents for a decade can be used to research the safety and effectiveness of anti-TNF agents in the long term. The objective of this article is to describe drug survival, disease activity, daily functioning, quality of life and adverse events of TNF-blocking agents in daily clinical practice after 5 years of follow-up. Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used for analyses (5-year follow-up, n=174). Drug survival and time to first serious infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome measures at several follow-up moments were analysed per intention to treat and per protocol. The 5-year drug survival of the first anti-TNF was 45%, and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was 5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d. 0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2). Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100 patient-years, respectively. Five-year follow-up of RA patients treated with TNF-blocking agents showed a 60% drug survival accompanied by sustained low disease activity, normalized function and quality of life similar to that in the general population. The benefit to risk ratio for long-term TNF-blocking therapy remains favourable.

Advanced Age Is an Independent Risk Factor for Severe Infections and Mortality in Patients Given Anti–Tumor Necrosis Factor Therapy for Inflammatory Bowel Disease

Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. We collected data from patients with IBD treated with infliximab (n = 2475) and adalimumab (n = 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn's disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death. Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died. Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients.

Efficacy of Anti-TNF in Crohns Disease: How Does it Work?

Several TNF antagonists, mainly monoclonal antibodies, have shown to be efficacious in the therapy of Crohn's disease. Despite the fact that they have been used for over a decade, their precise mechanism of action is still a matter of investigation. The effects of anti-TNF agents are mediated by multiple mechanisms including direct neutralization of soluble TNF and interaction with membrane-bound TNF. Anti-TNF agents may act by reduction of proinflammatory cytokine levels, elimination or clearance of active inflammatory cells from inflamed tissue which can conceptually be achieved by a number of mechanisms including apoptosis induction, antibody and complement mediated cytotoxicity and inhibition of cell migration into the intestinal tissue. Regulatory events both in the cellular and intracellular levels probably play a role as well. Finally, effects of anti-TNF agents may vary according to their physical contact with TNF leading to different binding avidities, conformational changes and variable downstream effects. These effects may also be influenced by structural differences in the non-TNF binding domain which affects the ability of each drug to interact with the immune system. Our understanding of these mechanisms of action is limited by the fact that much of the data was obtained using artificial in vitro systems of which their relevance to the in vivo situation is uncertain.

Can anti-TNF agents protect against rheumatoid arthritis-associated work disability?

The purpose of this perspective is to summarize recent literature on the effect of anti-TNF agents on work disability in patients with rheumatoid arthritis (RA). The current literature shows that the prevalence of work disability, including work cessation, sick leave and any other restriction in the work status, among patients with RA is substantial. In recent studies a trend towards a decline in work disability in RA is seen, which is considered to reflect improvements in drug treatment over the past decades. Overall, the number of studies on the effect of anti-TNF agents on work disability in RA is limited, with the majority being observational or having a nonrandomized design. In randomized controlled trials, in general a positive effect of anti-TNF agents on work disability in early RA was seen. Depending on the way productivity is valued, it was found that savings on productivity may compensate for the high costs of anti-TNF agents in early RA. In the future, more prospective studies on anti-TNF agen...

Anti-Tumor Necrosis Factor Agents Are Mostly Used in Patients with Established Rheumatoid Arthritis Compared to Early Disease — A Reflection of Adequate Clinical Practice

Almost 10 years after the introduction of the anti-tumor necrosis factor (TNF) agents for the treatment of rheumatoid arthritis (RA), rheumatologists are still struggling with their appropriate use and especially with the time to start them in the disease course. It is now well accepted that earlier disease control, i.e., suppression of inflammation, translates into better outcomes in terms of halting radiographic damage progression and preventing functional disability. Several clinical trials have shown the superiority of earlier use of combination methotrexate (MTX) and an anti-TNF agent1–3 compared to either agent used alone. However, given the cost of these new agents, economic considerations and the absence of predictive markers of response have prevented their use as first-line agents. Several national and international guidelines and consensus statements on the use of anti-TNF agents have been published4, the latest being the American College of Rheumatology recommendation document5. Except for the European registries, which deal mostly with safety issues, there is little information on the practical use and effectiveness of anti-TNF agents, especially in early disease versus established RA. The article by Lee, … Address correspondence to Dr. B. Haraoui, CHUM, Campus Notre-Dame, 1560 Sherbrooke est, Montreal, Quebec H2L 1S6. E-mail: bharaoui{at}videotron.ca