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The introduction of biological therapies, particularly anti-TNFα agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost “copies” of these drugs produced by competitor companies—referred to as biosimilars—are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease.

BACKGROUND: Recent neuroimaging studies have investigated the brain involvement in patients with Crohn's disease (CD) and Ulcerative Colitis (UC). Functional studies found abnormalities in cognitive and emotional functions in CD and UC, while a voxel based morphometry (VBM) study found morphological changes in CD. We conducted a VBM study to compare the gray matter (GM) volume of UC patients and controls. METHODS: Eighteen UC patients in remission and eighteen healthy controls underwent structural MRI. VBM is a fully automated technique allowing identification of regional differences in the amount of GM, which enables an objective analysis of the whole brain. VBM was used for comparisons between patients and controls. RESULTS: UC patients were all in remission and had a mild clinical course. There were no differences between patients and controls in GM volume. CONCLUSION: The brain morphology of patients with UC in remission is similar to controls. The lack of GM abnormalities in UC patients might reflect the mild clinical course of the inflammatory bowel disorder. Further research involving patients with different degrees of disease severity or during flares could shed more light on potential brain structural changes in UC.

L'Artemisia annua L. è una pianta erbacea annuale nota per la produzione del sesquiterpene antimalarico artemisinina. La produzione di artemisinina da parte della pianta è molto bassa e quasi esclusivamente prodotta nelle foglie e nelle infiorescenze, ed accumulata in specifiche strutture (tricomi ghiandolari) (Duke and Paul, 1993; Duke et al., 2009). Pertanto lo sviluppo di biotecnologie per la produzione di artemisinina in laboratorio è di notevole interesse. L'utilizzo di colture in vitro rappresenta una fonte alternativa alla pianta coltivata in campo. Da qui la necessità di sviluppare un valido protocollo per la messa a punto di sistemi in vitro che svincolino la produzione di artemisinina, nella pianta circoscritta ad alcuni organi e limitata a determinati periodi dell'anno, garantendo in questo modo una produzione costante ed efficace nel tempo. Nel nostro laboratorio sono stati allestiti diversi tipi di colture in vitro di A. annua (calli, sospensioni cellulari e piantine micropropagate), ottimizzando le condizioni di crescita mediante l'utilizzo di terreni di coltura con la stessa composizione chimica in macro- e microelementi, ma con ormoni di diverso tipo e concentrazione.

Biological therapiesareanimportantstepinthemanagementofInflammatoryBowelDiseases.Incon- sideration ofhighcostandsafetyissuesthereistheneedtohaveclearrecommendationsfortheiruse. Despite theAmericanGastroenterologicalAssociationandtheEuropeanCrohn’sandColitisOrganisation have publishedexhaustiveInflammatoryBowelDiseaseguidelines,nationalguidelinesmaybeneces- sary asculturalvalues,economicalandlegalissuesmaydifferbetweencountries.Forthesereasonsthe Italian SocietyofGastroenterologyandtheItalianGroupforthestudyofInflammatoryBowelDisease have decidedtoelaboratetheItalianguidelinesontheuseofbiologicsinInflammatoryBowelDisease. The followingitemshavebeenchosen:definitionsofactive,inactive,steroiddependentandresistant disease; measuresofactivity;anti-tumornecrosisfactoralphatherapyuseinactivesteroiddependent and refractoryluminalCrohn’sDisease,infistulisingCrohn’sDisease,insteroiddependentandresistant active UlcerativeColitis;riskofcancer;riskofinfectionsduringanti-tumornecrosisfactoralphatherapy; special situations.Theseguidelinesarebasedonevidencefromrelevantmedicalliteratureandclinical experience ofanationalworkinggroup.

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Background and aims: The widespread use of anti-tumour necrosis factor α antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. Methods: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (±5 years), site of CD, age at diagnosis (±5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. Results: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46-3.84); p = 0.40). The survival curve adjusted for patient year of follow up showed no differences between CD-IFX and CD-C (p = 0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD-IFX v CD-C: median 50 (range 40-70 years) v 45 (27-72); p = 0.50). Conclusion: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab.

Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

Revisione della terapia della pouchite

Nitric oxide is thought to play an important role in modulating the inflammatory process. Recently an increase in the inducible form of nitric oxide synthase (iNOS) has been found in the rat trinitrobenzene sulfonic acid model of experimental colitis, and inhibition of nitric oxide synthase activity resulted in an amelioration of tissue injury. The aim of our study was to evaluate in vivo intracolonic release of nitric oxide in this model of colitis. Experimental colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of trinitrobenzene sulfonic acid. Nitrite levels were determined in rectal dialysates by HPLC. The tissue myeloperoxidase and iNOS and the luminal leukotriene B4 were also measured. Nitrite levels were significantly increased in rectal dialysates during colitis and correlated significantly with tissue myeloperoxidase and iNOS activity. The correlation between nitrite dialysate levels and wall iNOS activity confirms that nitrite in dialysates is produced by inflammatory cells and not by colonic bacterial flora. Determination of nitrite levels in rectal dialysates seems a valuable method to monitor colonic inflammation in rat trinitrobenzene sulfonic acid colitis.

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