Maintenance treatment with infliximab for the management of Crohn’s disease in adults

Abstract

Crohn's disease (CD) is a chronic, relapsing disease, the continuous cycle of which deeply affects the long-term course which, eventually, leads to fi brosis and development of transmural complications. It is well known that CD is an immune-mediated clinical condition and that tumor necrosis factor-α (TNF-α) plays a fundamental role in the pathogenesis of the disease. Current clinical guidelines recommend that patients with mild to moderate active CD should be treated initially with corticosteroids. Although this approach is effective in inducing remission, some patients may become dependent on, or refractory to, these drugs in the long term, thus increasing the risk of developing steroid-related adverse effects. A recent Cochrane systematic review established that infl iximab (IFX) is effective in inducing remission in patients with CD. Although only a few published studies have assessed IFX for the maintenance of remission in the long term, there is evidence that IFX is superior to placebo in sustaining clinical remission and fi stula healing; moreover, corticosteroid-sparing effects have been demonstrated. IFX is associated with the formation of antibodies to IFX which can lead to infusion reactions and shorter duration of response, but when comparing episodic vs scheduled maintenance treatment, the latter appears to sensibly reduce immunogenicity, thus offering improved effi cacy and tolerance. The fi nal point to consider is the best time to introduce IFX in the therapeutic algorithm of CD. Early use of IFX has been suggested to be more effective than late, and may potentially change the natural history of the disease. Effective induction and maintenance therapy with IFX is the only means with which to maintain long-lasting clinical and mucosal remission which, in turn, may modify the long-term course of the disease. Furthermore, when treating infl ammatory bowel disease patients with IFX, an appropriate risk-benefi t balance has to be taken into consideration, because the precise risk of serious adverse events associated with anti-TNF treatment in CD remains to be fully elucidated.

Immunogenicity of biologics in inflammatory bowel disease

“…There is evidence that scheduled treatment with IFX not only results in improved efficacy 69 compared with episodic treatment, but that this is associated with a reduced level of immunogenicity. 70 Clinicians should also consider administering a loading dose of a biologic at the commencement of therapy, because, in addition to achieving therapeutic levels rapidly, this has been reported to reduce immunogenicity, 71 as has intravenous hydrocortisone treatment immediately prior to infusion with IFX. 72 Potential limitations of the present study include the diversity of study design, patient populations, disease severity, concomitant therapies, assay methods and timing of the studies reviewed.…”

Onset of severe perianal disease in Crohnʼs disease under treatment with infliximab

“…9 It has been recently shown that patients suffering from nonfistulizing perianal CD may develop anal abscesses under treatment with infliximab. 8,10 But our patient did not suffer from perianal disease in the first appearance of the disease, and perianal disease appeared when she was under treatment with infliximab (and under sustained remission). This type of complication is quite surprising.…”

“…Infliximab is effective in obtaining and maintaining remission of CD, 8 and the safety profile has been confirmed by a recent retrospective study showing a rate of serious adverse events lower than 10%. 9 It has been recently shown that patients suffering from nonfistulizing perianal CD may develop anal abscesses under treatment with infliximab.…”

Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development

“…In addition to these observations are the approaches for scheduling treatment with infliximab that lead to improved efficacy and reduced immunogenicity compared to episodic treatment [77,78]. Bots et al, (2021) demonstrated reduced rates of anti-drug antibodies in IBD patients treated with combination therapy consisting of infliximab (RR 0.52), adalimumab (RR 0.31), golimumab (RR 0.29), certolizumab pegol (RR 0.30), and natalizumab (RR 0.20) [39].…”