TNF-alpha Antagonists Research Articles

P520. Accuracy of rapid fecal calprotectin test in monitoring Inflammatory Bowel Diseases under treatment with TNF-alpha antagonists

P520. Accuracy of rapid fecal calprotectin test in monitoring Inflammatory Bowel Diseases under treatment with TNF-alpha antagonists

Efficacy and safety of TNF-alpha antagonists in children with juvenile idiopathic arthritis who started treatment under 4 years of age

The experience in the use of tumour necrosis factor (TNF) antagonists in children below 4 years is limited, although there are some trials in the literature which support safety and efficacy under this age.

Efficacy and safety of TNF-alpha antagonists in children with juvenile idiopathic arthritis who started treatment under 4 years of age.

The aims of the study were to assess efficacy and safety of TNF-alpha antagonists (anti-TNF) in a cohort of patients with juvenile idiopathic arthritis (JIA) who began treatment under 4 years old and to assess relapse rate after methotrexate and/or anti-TNF withdrawal. We made a retrospective charts review of our non-systemic JIA patients treated with anti-TNF under 4 years of age between January 2006 and April 2013. Demographics, epidemiologic, clinical, laboratory data and rate of relapse after treatment withdrawal due to clinical remission were collected. Efficacy and safety end points included side effects (SE) and time to achieve clinical remission. We included 27 patients, 23 received etanercept and 4 adalimumab with a median age of 3.01 (range 0.88-3.97) years at anti-TNF beginning and 1.94 (range 0.18-5.44) and 2.39 (range 0.18-7.24) years of treatment and follow-up, respectively. All patients had previously received disease-modifying antirheumatic drugs at optimal dose. Nineteen patients reached clinical remission on treatment in a median time of 9.1 (range 6.23-21.17) months. Four of those relapsed during treatment. Six developed mild SE, mostly mild infections. No serious SE were described. Eleven patients who reached clinical remission relapsed after treatment withdrawal. None achieved clinical remission off treatment. Most patients reached clinical remission on anti-TNF. In our cohort of patients, etanercept and adalimumab were safe, with mostly mild infections and no serious SE. We observed a high relapse rate during treatment withdrawal.

Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists.

Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-α (tumor necrosis factor-α) raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products). This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-α antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF-κB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-α antagonists which should be submitted to regulatory agencies for evaluation.

SAT0345 Patient Perceptions, Attitudes and Concerns about Anti-TNF Drugs

BackgroundPatients' perceptions about the side effects of drugs can have major impact on compliance to treatment. This becomes especially important with newer therapies.ObjectivesTo evaluate the frequency of patient concerns about...

THU0262 Comparing Abatacept to Adalimumab, Etanercept and Infliximab as First or Second Line Agents in Patients with Rheumatoid Arthritis. Experience from the Rhumadata® Clinical Database and Registry

BackgroundThe order of use of biologic agents is still a question for debate. Phase III trial data in MTX-IR patients show comparable efficacy results across biologic agents and limited head-to-head...

Su1405 The Safety of Biologic Use in the Pregnant IBD Patient: Analysis of Patient Characteristics, Pregnancy and Neonatal Outcomes

Background: TNF alpha inhibitors are being increasingly used in IBD in women of fertile age. Studies to date have been mainly limited to case reports and case series with the largest observational cohort from 50 centres in the US. We aimed to prospectively assess the use of anti TNF treatment during pregnancy in a large European cohort. Methods: This was an observational cohort study addressing a 5 year period between 2008-2013. Female patients with IBD who had undergone anti-TNF treatment during pregnancy were identified using the IBD databases of 2 tertiary referral centres for IBD in Dublin. Patient characteristics including disease activity scores, duration, site and concomitant medications were recorded. Pregnancy outcomes including mode of delivery, miscarriage, ante and postnatal complications, age at conception and need for escalation of IBD treatment during pregnancy were also assessed. Neonatal outcomes including low birth weight, pre-term delivery, NICU stays or perinatal infection and timing of vaccines were also recorded. Data were analysed using t testing, contingency and logistic regression analyses. Results: From an IBD population of over 2,500 patients, 31 individual females who underwent anti -TNF treatment during pregnancy from 2008-2013 were identified with a total of 36 pregnancies. Median disease duration at time of pregnancy was 12 years (IQR 3-17). 85% had Crohn's Disease, 15% Ulcerative Colitis. Median Harvey Bradshaw Index pre-pregnancy was 4.5 (IQR 2-13). Median Mayo score was 1 (IQR 0-3). 57.3% received infliximab, 38% adalimumab, 4.7% certolizimab. 53.8% were on concomitant immunemodulators. The majority of patients stopped biologic treatment at the start of the third trimester. 67% had treatment reinstated in the postpartum period. Median age at conception was 30.5 (IQR 25-35). 19% had previous miscarriages. 92% had successful term pregnancies. 22% required escalation of treatment during pregnancy. 19.3% had a pregnancy complication including emergency section. 16% neonates had a low birth weight with 2 preterm deliveries and one case of NICU stay for meconium ileus. No perinatal infections were reported. 20%mothers breastfed. The majority of mothers delayed live vaccination of their children. Interestingly, there was a significant independent association between disease activity at time of conception and low birthweight (p < 0.01). There was no association between adverse outcomes or neonatal infections and anti-TNF use noted in this cohort.Conclusion: Disease control at time of conception and through pregnancy should be the main goal of treatment in this patient cohort and the use of TNF alpha antagonists to achieve this appears to warranted to improve pregnancy outcomes though definitive safety has yet to be proven.

Su1406 Efficacy, Safety, and Demographics Factor of Adalimumab Therapy in 1693 Japanese Crohn's Disease Patients

Background: TNF alpha inhibitors are being increasingly used in IBD in women of fertile age. Studies to date have been mainly limited to case reports and case series with the largest observational cohort from 50 centres in the US. We aimed to prospectively assess the use of anti TNF treatment during pregnancy in a large European cohort. Methods: This was an observational cohort study addressing a 5 year period between 2008-2013. Female patients with IBD who had undergone anti-TNF treatment during pregnancy were identified using the IBD databases of 2 tertiary referral centres for IBD in Dublin. Patient characteristics including disease activity scores, duration, site and concomitant medications were recorded. Pregnancy outcomes including mode of delivery, miscarriage, ante and postnatal complications, age at conception and need for escalation of IBD treatment during pregnancy were also assessed. Neonatal outcomes including low birth weight, pre-term delivery, NICU stays or perinatal infection and timing of vaccines were also recorded. Data were analysed using t testing, contingency and logistic regression analyses. Results: From an IBD population of over 2,500 patients, 31 individual females who underwent anti -TNF treatment during pregnancy from 2008-2013 were identified with a total of 36 pregnancies. Median disease duration at time of pregnancy was 12 years (IQR 3-17). 85% had Crohn's Disease, 15% Ulcerative Colitis. Median Harvey Bradshaw Index pre-pregnancy was 4.5 (IQR 2-13). Median Mayo score was 1 (IQR 0-3). 57.3% received infliximab, 38% adalimumab, 4.7% certolizimab. 53.8% were on concomitant immunemodulators. The majority of patients stopped biologic treatment at the start of the third trimester. 67% had treatment reinstated in the postpartum period. Median age at conception was 30.5 (IQR 25-35). 19% had previous miscarriages. 92% had successful term pregnancies. 22% required escalation of treatment during pregnancy. 19.3% had a pregnancy complication including emergency section. 16% neonates had a low birth weight with 2 preterm deliveries and one case of NICU stay for meconium ileus. No perinatal infections were reported. 20%mothers breastfed. The majority of mothers delayed live vaccination of their children. Interestingly, there was a significant independent association between disease activity at time of conception and low birthweight (p < 0.01). There was no association between adverse outcomes or neonatal infections and anti-TNF use noted in this cohort.Conclusion: Disease control at time of conception and through pregnancy should be the main goal of treatment in this patient cohort and the use of TNF alpha antagonists to achieve this appears to warranted to improve pregnancy outcomes though definitive safety has yet to be proven.

Risk of breast cancer and total malignancies in rheumatoid arthritis patients undergoing TNF-α antagonist therapy: a meta-analysis of randomized control trials.

Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA). To analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs). A systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-α antagonists with placebo or methotrexate (MTX) (or TNF-α antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNotex6. Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies. 28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-α therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis. This study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-α antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-α antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses.

Infections in patients affected by rheumatologic diseases associated to glucocorticoid use or tumor necrosis factor-alpha inhibitors

A great diversity of infectious agents can affect patients that use steroids at immunosuppressive doses or tumor necrosis factor alpha (TNF-alpha) antagonists. The list of participating microorganisms is more restricted in the case of anti TNF-alpha blockers. Overlapping agents include intracellular bacteria, Mycobacterium tuberculosis, geographic fungal agents that have the ability to establish granulamotous infections, herpes zoster, and reactivation of chronic hepatitis B virus infection. An important conceptual issue for these infections is the existence of a threshold prednisone daily dose for the emergence of opportunistic infections but higher levels of immunosuppression and cofactors are required in the case of Pneumocystis jiroveci and cytomegalovirus infections. In order to prevent these threats, a detailed medical evaluation is needed before prescription to detect potential risks and manage them properly. Prevention rules must be prescribed in every case, that include common sense behaviors, vaccines, and in selected cases, chemoprophylaxis for latent tuberculosis (TB) infection, P. jiroveci pneumonia (PCP) or other specific requirements. Latent TB infection is probable and requires chemoprophylaxis in the case of remote or recent exposure to a patient with lung TB, a positive tuberculin or interferon-gamma release assay result or residual lung scars in a chest x-ray exam. PCP prevention is suggested when the patient reaches a daily dose of prednisone of 30 mg but might be needed at lower doses in case of other concomitant immunosuppressive drugs or when lymphopenia arises shortly after prednisone initiation.

P337 TNF-alpha as induction therapy for Crohn's disease: a comparison of adalimumab and infliximab – a prospective observational study in Germany

scores, duration, site and concomitant medications were recorded. Pregnancy outcomes including mode of delivery, miscarriage, ante/postnatal complications, age at conception and need for escalation of IBD treatment during pregnancy were also assessed. Neonatal outcomes including low birth weight, pre-term delivery, NICU stays or perinatal infection and timing of vaccines were also recorded. Data were analysed using t testing, contingency and logistic regression analyses. Results: From an IBD population of over 2,500 patients, 31 individual females who underwent anti-TNF treatment during pregnancy from 2008 2013 were identified with a total of 36 pregnancies. Median disease duration at time of pregnancy was 12 years (IQR 3 17). 85% had Crohn’s Disease, 15% Ulcerative Colitis. Median Harvey Bradshaw Index pre-pregnancy was 4.5 (IQR 2 13). Median Mayo score was 1 (IQR 0 3). 57.3% received infliximab, 38% adalimumab, 4.7% certolizimab. 53.8% were on concomitant immunemodulators. The majority of patients stopped biologic treatment at the start of the third trimester. 67% had treatment reinstated in the postpartum period. Median age at conception was 30.5 (IQR 25 35). 19% had previous miscarriages. 92% had successful term pregnancies. 22% required escalation of treatment during pregnancy. 19.3% had a pregnancy complication including emergency section. 16% neonates had a low birth weight with 2 preterm deliveries and one case of NICU stay for meconium ileus. No perinatal infections were reported. 20% mothers breastfed. The majority of mothers delayed live vaccination of their children. Interestingly, there was a significant independent association between disease activity at time of conception and low birthweight (p < 0.01). There was no association between adverse outcomes or neonatal infections and anti-TNF use noted in this cohort. Conclusions: Disease control at time of conception and through pregnancy should be the main goal of treatment in this patient cohort and the use of TNF alpha antagonists to achieve this appears to warranted to improve pregnancy outcomes though definitive safety has yet to be proven.

The potential additional benefit of infliximab in patients with chronic pulmonary sarcoidosis already receiving corticosteroids: A retrospective analysis from a randomized clinical trial

Infliximab, a TNF-alpha antagonist, has shown efficacy in the treatment of sarcoidosis. Since corticosteroids inhibit TNF-alpha expression, we postulated that sarcoidosis patients receiving a sufficient corticosteroid dose may have an attenuated response to the addition of infliximab. We analyzed data from a previous randomized double blind prospective trial of infliximab versus placebo for chronic pulmonary sarcoidosis. The effect of the maintenance corticosteroid dose on the change in FVC % predicted between 0 and 24 weeks (ΔFVC%pred0-24) was analyzed in two ways. First, the mean ΔFVC%pred0-24 was calculated for the placebo and infliximab groups using three different daily prednisone equivalent dose thresholds: a) <10mg versus ≥10mg; b) <15mg versus ≥15mg; c) <20mg versus ≥20mg. Second, in both the placebo and infliximab groups, a correlation coefficient was calculated between the maintenance corticosteroid dose and ΔFVC%pred0-24. Both the group that received infliximab and either a maintenance daily dose of <10mg of prednisone and the group receiving ≥10mg had a significant increase in FVC%pred0-24. However, both the groups that received infliximab and a corticosteroid dose of >15mg of prednisone and ≥20mg of prednisone did not demonstrate a significant ΔFVC%pred0-24. For the placebo group, there was no significant correlation between the corticosteroid dose and the ΔFVC%pred0-24. For the infliximab group, there was a significant correlation (p=0.0097) between higher corticosteroid dose and less improvement in FVC%pred0-24. Our results suggest that infliximab adds minimal potential benefit to corticosteroids for pulmonary sarcoidosis at doses above 15-20mg/day of prednisone.

Exacerbation of recalcitrant cutaneous sarcoidosis with adalimumab - a paradoxical effect? A case report

The paradoxical adverse effects of tumor necrosis factor-alpha (TNF-alpha) antagonists have been described frequently as a result of the widespread use of these drugs. Among the TNF-alpha blocking agents, few reports exist relating the use of adalimumab in cutaneous sarcoidosis, although all of them show good results. More recently, sarcoidosis onsets have been reported with various TNF-alpha inhibitors. The current case is, to our knowledge, the first to describe the exacerbation of cutaneous lesions of sarcoidosis treated with adalimumab.

PReS-FINAL-2315: Severe cutaneous vasculitis in two patients with juvenile idiopathic arthritis and biologic therapy

The management of chronic inflammatory autoimmune diseases has been revolutioned by the use of novel biologic agents achieving excellent results in the treatment of Juvenile Idiopathic Arthritis (JIA). These drugs are generally well tolerated but as they are increasingly used, the incidence of adverse reaction is more common. The most frequent are localised at the injection's site; others include: pustular folliculitis, psoriasis, hydradenitis, Sweet's syndrome, lupus-like reactions, and palm plantar pustolosis. Cutaneous vasculitis related to TNF-alpha antagonists, such as hypersensitivity and leucocytoclastic vasculitis, has been described as few case reports. Conversely, there are no reports of cutaneous vasculitis induced from other biologic agents. We report two cases of severe cutaneous vasculitis in adolescents with JIA and uveitis under biologic therapy.

Efficacy of infliximab in neuro-Behçet’s disease presenting with isolated longitudinally extensive transverse myelitis

Efficacy of infliximab in neuro-Behçet’s disease presenting with isolated longitudinally extensive transverse myelitis

Clinical aspects and management of cutaneous leishmaniasis in rheumatoid patients treated with TNF-α antagonists

Patients under immunosuppressive therapy with tumor necrosis factor alpha (TNF-α) antagonists are vulnerable to various opportunistic infections including leishmaniasis. We present a case series of 8 travellers developing cutaneous leishmaniasis whilst on TNF-α antagonist treatment and review the literature on aspects of cutaneous leishmaniasis developing in patients treated with TNF-α antagonists. We make interim recommendations regarding the drug therapy used to maintain remission in travellers with rheumatoid disease travelling to leishmania prone areas. Despite having a medical condition requiring continued rheumatological review the interval to diagnosis appears not to be reduced compared to that described in non-rheumatoid patients. Rheumatologists and family doctors should be aware of the need for post-travel surveillance for leishmaniasis in rheumatoid patients on TNF-alpha antagonist treatment.

Bacteremia in patients receiving TNF-alpha antagonists – A prospective multicenter study

TNF-alpha antagonists have changed the outcome of various chronic inflammatory diseases. Their use has spread widely and many patients receive those treatments for years. Previous reports found that the use of TNF-alpha antagonists may be associated with an increased risk of serious bacterial infections. We report 47 prospective bacteremia cases from the RATIO registry. A national prospective study was conducted in France between 2004 and 2007 to collect severe bacterial infections in patients receiving TNF-alpha antagonists. All reported cases of bacteremia were validated by an expert committee. Forty-seven bacteremic episodes were reported. Staphylococcus aureus represented the most frequent causative pathogen (40%) and was mostly associated with bones and/or joints infections (68%) and with a worse outcome compared to that observed with other bacterial pathogens. Patients receiving TNF-alpha antagonists may develop bacteremia and S. aureus has to be included in the spectrum of the initial empiric antimicrobial therapy.

Generalized erythroderma and palmoplantar hyperkeratosis in a patient receiving TNF-alpha antagonist therapy

Journal of Cutaneous PathologyVolume 40, Issue 9 p. 855-856 Letter to the Editor Generalized erythroderma and palmoplantar hyperkeratosis in a patient receiving TNF-alpha antagonist therapy Karin M. Dunst-Huemer MD, Corresponding Author Karin M. Dunst-Huemer MD Department of Dermatology and Venerology, General Hospital Linz, Linz, Austriae-mail: [email protected]Search for more papers by this authorChristine Scheurecker MD, Christine Scheurecker MD Department of Dermatology and Venerology, General Hospital Linz, Linz, AustriaSearch for more papers by this authorJosef Auboeck MD, Josef Auboeck MD Department of Dermatology and Venerology, General Hospital Linz, Linz, AustriaSearch for more papers by this author Karin M. Dunst-Huemer MD, Corresponding Author Karin M. Dunst-Huemer MD Department of Dermatology and Venerology, General Hospital Linz, Linz, Austriae-mail: [email protected]Search for more papers by this authorChristine Scheurecker MD, Christine Scheurecker MD Department of Dermatology and Venerology, General Hospital Linz, Linz, AustriaSearch for more papers by this authorJosef Auboeck MD, Josef Auboeck MD Department of Dermatology and Venerology, General Hospital Linz, Linz, AustriaSearch for more papers by this author First published: 29 June 2013 https://doi.org/10.1111/cup.12188Citations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume40, Issue9September 2013Pages 855-856 RelatedInformation

Spondyloarthritis Associated with Acne Conglobata, Hidradenitis Suppurativa and Dissecting Cellulitis of the Scalp: A Review with Illustrative Cases

To review and highlight the association of acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp with inflammatory arthritic conditions, we report five illustrative patients with this association, and a review of the literature. All our patients were African-American males, and their skin disease present before the onset of arthritis. Both asymmetric peripheral arthritis and axial disease can occur. The arthritis is usually insidious and lacks association with rheumatoid factor and HLA-B27. Imaging of peripheral joints can reveal erosions, periosteal bone reaction and new bone formation. When the axial skeleton is involved, imaging can reveal sacroiliitis, syndesmophyte formation. NSAIDs, oral and intra-articular steroids, DMARDs and TNF alpha antagonists have all been used with success. Controlled trials with larger numbers of patients are needed to assess which treatment options are the most effective for this group of patients.

FRI0357 Certolizumab pegol is effective in children with JIA not responsive to other TNF alpha antagonists

BackgroundPatients with polyarticular juvenile idiopathic arthritis (JIA) may not respond sufficiently to methotrexate (MTX) combined with TNF Alpha antagonists (TNFA). In this cases switching to another TNFA might be beneficial....