Influence of anti-tumor necrosis factor-alpha therapy to pregnant inflammatory bowel disease women and their children's immunity

BACKGROUND/AIMS: The onset of inflammatory bowel disease (IBD) usually occurs at young age, and therefore, women IBD patients experience pregnancy during their disease progression. Recently, the use of anti-tumor necrosis factor-α (anti-TNF-α) has been rapidly increasing. The aim of this study was to evaluate pregnancy related outcomes in women with IBD who were treated with anti-TNF-α during pregnancy and immunity of their children. METHODS: Korean women with IBD who had been treated with anti-TNF-α during pregnancy had been enrolled. Medical records were reviewed and a survey was performed for each patient. For the patients who agreed on additional examination for their children, children's growth, medical history and antibody to hepatitis B surface antigen (anti-HBs) titer were checked. RESULTS: All 18 patients had been diagnosed with Crohn's disease. There was not any case of preterm delivery, low birth-weight infant, congenital anomaly, nor stillbirth. All 12 children had followed the regular vaccination schedule for hepatitis B and 4 of them showed negative results for anti-HBs. After the 1 booster vaccination, all children demonstrated seroconversion. Regarding live vaccines, 4 children had bacillus Calmette-Guerin and 4 had rotavirus vaccine before 6 months, without any specific side effects. CONCLUSIONS: This was the first study of immunity of the children born from IBD women who had been treated with anti-TNF-α medication during their pregnancy. IBD women had comparable pregnancy outcomes with the general women population, suggesting that the disease activity rather than the administered medication would be more important in healthy pregnancy. Considering the history of vaccination and anti-HBs titers, immunity seems to be intact in the children.

Anti-Tumor Necrosis Factor Therapy in Intestinal Behçet's Disease

Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor–α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor–α for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor–α, including vulnerability to infections and malignancy.

Controversy and consensus of the anti-tumor necrosis factor alpha in the treatment of Crohn's disease with intestinal stricture / 中华消化外科杂志

The emergence of the anti-tumor necrosis factor alpha(anti-TNF-α)therapies has brought lots of benefits to patients with inflammatory bowel disease(IBD).However,controversies exist over whether anti-TNF-α could be used for Crohn's disease(CD)patients with intestinal stricture.Some articles found stricturing CD patients under anti-TNF therapy had a high risk of intestinal obstruction or even perforation while others found that there was no association between anti-TNF-α and intestinal obstruction.The fundamental cause lies in that anti-TNF-α only target at inflammation,but cannot be resistant to intestinal fibrosis or change long term outcome.To avoid and prevent intestinal obstruction or perforation,authors should evaluate the component and type of intestinal stricture cautiously before starting anti-TNF-α therapy.Exploring new specific antifibrotic therapy will be a promising way for all stricturing CD patients.

Paradoxical reactions induced by tumor necrosis factor-alpha antagonists: A literature review based on 46 cases.

Anti-tumor necrosis factor (TNFα) agents have acquired a prominent place in the treatment options for infl ammatory disorders. Among the side effects of these agents are the so-called paradoxical reactions which have increasingly been reported in recent years. A review of literature was carried out using Medline (PubMed) database from January 2010 to December 2014 to collect all published articles on cases of anti-TNFα-induced psoriasis and psoriatic arthritis. Published articles were identifi ed, reviewed and the relevant data extracted. A total of 22 studies (46 patients) fulfi lled the inclusion criteria and were selected for analysis. Of the 46 patients, 45 (97.8%) developed psoriasis and 1 (2.1%) psoriatic arthritis. The mean age of patients was 47 years; three (6.5%) patients had a past history of psoriasis. Infl iximab caused cutaneous reactions in the most number, 26 (56.5%) cases. Thirty seven (80.4%). patients developed primary plaque-type psoriasis. Women accounted for 86.9% of patients. There was complete resolution of psoriasis in 12 (26%) patients despite differences in the therapeutic approach. Cessation of the incriminated drug led to resolution of cutaneous lesions in 5 (10.8%), switching to another TNFα antagonist led to resolution in 6 (13%) and one (2.1%) patient improved despite continuation of the drug. As for the lone case of psoriatic arthritis, drug withdrawal did not result in improvement; only switching to another anti-TNFα agent helped. Since our sample was small, it was not adequately powered to draw any fi rm conclusions. However, in this analysis, we found that paradoxical reactions occurred predominantly in adult women, there were only isolated cases with a personal history of psoriasis, infl iximab was responsible for most cases of these reactions and the most prevalent form was plaque-type psoriasis. The decision whether to continue or discontinue the triggering anti-TNFα agent should be individualized as results are highly variable.

Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan

BACKGROUND/AIMS: Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines. METHODS: This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines. RESULTS: Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037). CONCLUSIONS: Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.

Iliopsoas Abscess Misconstrued as Aggravated Ankylosing Spondylitis / 대한내과학회지

An iliopsoas abscess is a collection of pus in the iliopsoas muscle caused by the direct spread of infection from adjacent internal organs or by hematogenous or lymphatic spread from distal sites. Its symptoms are vague back, hip, thigh or lower abdomen pain with insidious onset, similar to those of ankylosing spondylitis (AS). Therefore diagnosing an iliopsoas abscess in patients with AS is difficult. A forty-three year-old man was treated with adalimumab, a tumor necrosis factor inhibitor, and clinical symptoms were subsequently observed to improve. One year after voluntary discontinuation of adalimumab, the patient returned with a recurrence of right buttock pain and was diagnosed as having aggravated AS. Following re-initiation of adalimumab, symptoms did not improve and fever developed. On the basis of imaging studies, the patient was diagnosed as having an iliopsoas abscess and was successfully treated with intravenous antibiotics.

Body Weight and Bone Density Changes in Patients with Ankylosing Spondylitis Receiving Anti-Tumor Necrosis Factor-alpha Treatment / 대한내과학회지

BACKGROUND/AIMS: To determine the changes in body weight and bone mineral density in patients with ankylosing spondylitis (AS) receiving anti-tumor necrosis factor-alpha (TNF-alpha) treatment. METHODS: Thirty-one patients with AS (25 males and 6 females) who fulfilled the Modified New York Criteria for AS were included in this retrospective study. All patients had active disease that eventually required anti-TNF-alpha treatment. Each patient received anti-TNF-alpha treatment (etanercept 25 mg twice weekly or adalimumab 40 mg twice monthly) for more than 2 years. Body weight, disease activity as Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein, erythrocyte sedimentation rate (ESR), lumbar bone mineral density (LBMD), and femoral bone mineral density (FBMD) were measured at baseline and at 1 and 2 years after initiating anti-TNF-alpha treatment. RESULTS: There was a significant increase in mean body weight at 1 year (1.1 +/- 3.8 kg) and at 2 years (1.7 +/- 4.8 kg) compared with baseline. The gains in mean BMD of the lumbar spine were significant at 1 year (0.4 +/- 0.4) and 2 years (0.5 +/- 0.7) compared with baseline. Mean BMD of the femur was also increased at 1 year (0.08 +/- 0.7) and 2 years (0.1 +/- 0.8) compared with baseline, but these differences were not statistically significant. There were significant decreases in BASDAI at 1 year (-3.3 +/- 2.8) and at 2 years (-3.6 +/- 2.8) compared with baseline. CONCLUSIONS: This study showed significant increases in body weight, lumbar BMD, and BASDAI at 1 year and 2 years in patients with ankylosing spondylitis after receiving anti-TNF-alpha treatment.

Body Weight and Bone Density Changes in Patients with Ankylosing Spondylitis Receiving Anti-Tumor Necrosis Factor-alpha Treatment / 대한내과학회지

BACKGROUND/AIMS: To determine the changes in body weight and bone mineral density in patients with ankylosing spondylitis (AS) receiving anti-tumor necrosis factor-alpha (TNF-alpha) treatment. METHODS: Thirty-one patients with AS (25 males and 6 females) who fulfilled the Modified New York Criteria for AS were included in this retrospective study. All patients had active disease that eventually required anti-TNF-alpha treatment. Each patient received anti-TNF-alpha treatment (etanercept 25 mg twice weekly or adalimumab 40 mg twice monthly) for more than 2 years. Body weight, disease activity as Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein, erythrocyte sedimentation rate (ESR), lumbar bone mineral density (LBMD), and femoral bone mineral density (FBMD) were measured at baseline and at 1 and 2 years after initiating anti-TNF-alpha treatment. RESULTS: There was a significant increase in mean body weight at 1 year (1.1 +/- 3.8 kg) and at 2 years (1.7 +/- 4.8 kg) compared with baseline. The gains in mean BMD of the lumbar spine were significant at 1 year (0.4 +/- 0.4) and 2 years (0.5 +/- 0.7) compared with baseline. Mean BMD of the femur was also increased at 1 year (0.08 +/- 0.7) and 2 years (0.1 +/- 0.8) compared with baseline, but these differences were not statistically significant. There were significant decreases in BASDAI at 1 year (-3.3 +/- 2.8) and at 2 years (-3.6 +/- 2.8) compared with baseline. CONCLUSIONS: This study showed significant increases in body weight, lumbar BMD, and BASDAI at 1 year and 2 years in patients with ankylosing spondylitis after receiving anti-TNF-alpha treatment.