Prescribing Patterns and Awareness of Adverse Effects of Infliximab: A Health Survey of Gastroenterologists

We sought to determine prescribing patterns and awareness of adverse drug reactions to infliximab among gastroenterologists. A questionnaire was developed and mailed to all gastroenterologists in Maryland and Washington, D.C. Ninety-six of 336 (28.6%) gastroenterologists responded; 86% of respondents use infliximab often or sometimes and 48% infuse infliximab on-site. Only 48% of respondents use immunomodulators prior to infusing infliximab. Thirty-three percent of respondents do not prescribe maintenance infliximab. Respondents reported that infusion reactions occur in 12.9% of infliximab infusions. Most respondents order a purified protein derivative prior to starting infliximab. Respondents underestimated the risk of serious infection, death, demyelinating diseases, and malignancy and overestimated the risk of congestive heart failure. We conclude that a substantial number of gastroenterologists underutilize immunomodulators and fail to prescribe maintenance infliximab. Further, respondents were unaware of the frequency of major adverse events associated with infliximab. Education regarding treatment algorithms in CD and infliximab-related side effects is needed.     

Isolated renal sarcoidosis: a rare presentation of a rare disease treated with infliximab

Sarcoidosis is a multisystem disease characterized by noncaseating granulomatous reaction frequently involving the lymph nodes, lungs, liver, skin, and eyes. Acute renal failure (ARF) as an isolated manifestation of sarcoidosis is rare. We describe a case of sarcoidosis presenting as transient polyarthritis and ARF due to isolated granulomatous infiltration of the renal parenchyma. Renal biopsy showed granulomatous interstitial nephritis with noncaseating granulomas consistent with sarcoidosis. Bacterial, fungal, and mycobacterial infections were excluded. There was no evidence of extrarenal sarcoid involvement. Prednisone of 60 mg daily resulted in significant improvement in renal function. Because of recurrent flares on steroid taper and steroid toxicity, treatment with infliximab, an anti-tumor necrosis factor-α (TNF-α) antibody, was instituted and resulted in stabilization of renal function despite steroid taper. Although uncommon, renal sarcoidosis should be considered in the differential diagnosis of acute or chronic renal failure of uncertain etiology, as early diagnosis and treatment can lead to recovery of renal function and prevent interstitial fibrosis. Corticosteroids are mainstay of therapy. Steroid-dependant or refractory cases may respond to other immunosuppressants including anti-TNF-α agents.     

Medical options for treating perianal Crohn's disease

Perianal Crohn's disease can cause significant morbidity for patients affected by the disease. However, diagnostic modalities and treatment options have progressed changing the goals of treatment from fistula "improvement" to complete cessation of drainage. Fistula closure and fibrosis of the fistula track is achieved in some patients. Furthermore, treatment has become a combined effort between medical physicians and surgeons. Simple disease can be treated with medical therapy alone consisting of antibiotics and immunomodulators. Infliximab should be added to refractory simple disease or simple disease with the presence of inflammation. If complex fistula disease is evident a surgical evaluation should also be done to determine if intervention is indicated. Complex disease should be treated with antibiotics, immunomodulators and biologic therapy from the onset. This review will summarise current data regarding medical options for treatment of fistulising Crohn's disease.     

Gangrenous pyoderma and enterocutaneous fistulas after ileal pouch-anal anastomosis

We describe the medical-surgical management of a patient with a complex inflammatory bowel disease who developed 2 acute episodes of pyoderma gangrenosum and enterocutaneous fistulas after ileal pouch-anal anastomosis for ulcerative colitis. The rarity of this postsurgical complication is emphasized. A good response to topical tacrolimus was achieved in cutaneous wounds. A less favorable response to infliximab was achieved in the abdominal fistulas, requiring surgical excision of the pouch.     

New antirheumatic drugs: any real added value? A critical overview of regulatory criteria for their marketing approval

Objective

Rheumatoid arthritis (RA) is a systemic autoimmune disorder causing chronic polyarticular synovial inflammation and progressive joint damage. New anti-rheumatic drugs, such as leflunomide, infliximab, etanercept, adalimumab and anakinra, have recently become available. The aim of this paper is to summarize and critically evaluate the type of studies and clinical endpoints accepted by the European Medicines Agency (EMEA) to approve these new drugs.

Materials and methods

Information regarding the approval of antirheumatic drugs was obtained from European Public Assessment Reports (EPARs) and published pivotal studies.

Results

Leflunomide is the only non-biological disease-modifying anti-rheumatic drug (DMARD) to receive recent approval for RA treatment, but strong evidence of its superiority over conventional therapies is lacking. Anakinra in combination with methotrexate received approval as a DMARD for RA on the basis of two pivotal trials in which American College of Rheumatology response criteria (ACR 20 response) were used as the sole primary endpoint. For easier demonstration of efficacy, studies leading to first approval of etanercept, infliximab and adalimumab were carried out on non-responders to DMARDs. Once on the market, these drugs gained an extension of the indication to methotrexate-naïve patients. Studies that provided the basis for approval were not adequately designed, given the lack of an active control and the choice of ACR response as the only clinical endpoint. Consequently, only a weak proof of efficacy emerged for the treatment of signs and symptoms of RA, and these drugs failed to show real benefit in slowing radiographic progression. Serious infections, changes in blood cell counts, severe skin and hepatic infections were the main adverse events that emerged from the clinical studies. Therefore, the unconvincing benefit of the new antirheumatic drugs can scarcely outweigh the risk associated with their use. Moreover, the monthly costs in Italy of the new biological preparations are several fold higher than those of the reference drugs.

Conclusions

Recently approved anti-RA products should be a therapeutic option only for patients refractory to conventional drugs.

     

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

Background/AimsAnti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients.MethodsPediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this cross-sectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors.ResultsA total of 76 patients (Crohn’s disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%).ConclusionsIFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.     

Successful Treatment with Infliximab for Behçet Disease during Pregnancy

Purpose: To report a case of successful treatment with infliximab for Behçet disease (BD) during pregnancy. Design: A case report.

Methods: A 30-year-old woman was diagnosed with BD at 12 weeks of pregnancy. Additional symptoms occurred, and infliximab at a dose of 5?mg/kg body weight was initiated at 18 weeks and repeated.

Results: All symptoms improved, and a 3950-g infant was delivered uneventfully without any abnormality at 39 weeks. A few weeks after delivery, uveitis and systemic symptoms relapsed. Infliximab was reinitiated and all symptoms were resolved.

Conclusions: Infliximab may be safe and effective for BD during pregnancy.     

Switching the therapy from etanercept to infliximab in a child with rheumatoid factor positive polyarticular juvenile idiopathic arthritis

Abstract

Tumor necrosis factor α (TNFα)-blocking agents have been used increasingly in the treatment of severe refractory juvenile idiopathic arthritis (JIA). However, some patients have been forced to discontinue these agents because of the lack of efficacy or adverse events. In these situations, cases of switching from one TNF-blocking agent to another are reported in rheumatoid arthritis, but there are few cases in JIA. This report documents the case of a patient with JIA who improved following a switch from etanercept to infliximab.     

Noninfectious interstitial lung disease during infliximab therapy:Case report and literature review

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases.However,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is also emerging for biologics.We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab.She was referred to our clinic with a severe relapse and was treated with infliximab,an antitumor necrosis factor α(TNF-α)antibody,to induce remission.After an initial benefit,with decreases in bowel movements,rectal bleeding and C-reactive protein levels,she experienced shortness of breath after the 5thinfusion.Noninfectious interstitial lung disease was diagnosed.Both mesalamine and infliximab were discontinued,and steroids were introduced with slow but progressive improvement of symptoms,radiology and functional tests.This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations.Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases,this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.     

Steroid-refractory ulcerative colitis and associated primary sclerosing cholangitis treated with infliximab

Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative colitis.Damage to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually ineffective.We describe a patient with long-standing ulcerative colitis,which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis(biochemical stage Ⅱ/Ⅳ) in the course of his pancolitis.Treatment with infliximab(5 mg/kg as an induction dose followed by maintenance doses every two months) was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprinerelated hepatic toxicity.At present,after two years of follow-up,the patient is asymptomatic with normal liver tests and complete resumption of daily life activities.This case draws attention to the usefulness of antitumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease.