Infliximab in the treatment of Crohn''s disease: Predictors of response in an Italian multicentric open study

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.     

Agentes anti-factor de necrosis tumoral en enfermedad de Crohn y colitis ulcerosa: más allá de la enfermedad luminal

Anti-tumor necrosis factor agents (anti-TNF) drugs are commonly used in patients with inflammatory bowel disease (IBD) and have proven effective in both induction and maintenance therapy in luminal Crohn's disease and ulcerative colitis. Their efficacy has also been proven in fistulising perianal Crohn's disease. However, the evidence in other scenarios, such as stricturing, penetrating and non-fistulising perianal Crohn's disease, extraintestinal IBD manifestations and ileoanal reservoir complications, is not as robust. The aim of this review was to perform an analysis of the available literature and to determine the role of anti-TNF drugs in common clinical practice in patients affected by these complications.     

Approach to medical therapy in perianal Crohn’s disease

Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn’s disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.     

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience

During infliximab treatment of perianal Crohn's disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10+/-2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4+/-8.8 months (range 3-28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25+/-5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.     

Anti-TNF strategies in stenosing and fistulizing Crohn’s disease

Background Stenoses and fistulas are frequent complications in patients with Crohns disease (CD). They represent a major diagnostic and therapeutic challenge and surgical intervention is often required. The availability of novel, anti-TNF strategies for therapy has raised the question as to what extent these new treatment options have impact on the clinical decision-making process regarding the necessity for surgery.Discussion A short overview of the current pathophysiological understanding of CD, focusing on the immunology of the intestinal mucosa, is given. Then the problems of proper clinical management of stenoses and fistulas are addressed. With regard to symptomatic stenoses, attention will be given to novel diagnostic tools for the distinction between inflammatory and fibrotic stenoses, and our clinical experience with the treatment of symptomatic inflammatory stenoses with infliximab will be discussed. With regard to fistulizing CD, the data that are currently available for medical therapy are summarized with special reference to the studies on the efficacy of anti-TNF treatment.Conclusion With regard to moderately and severe inflammatory stenoses, medical treatment with infliximab may be an option after careful assessment of the inflammatory nature of the stenosis and exclusion of a septic focus. With regard to fistulas, anti-TNF treatment is a valuable option that is likely to improve the clinical outcome. Based on the available data, however, anti-TNF treatment cannot yet replace surgical intervention when necessary. Prospective trials of medical therapy and a combination of medical and surgical therapy for complex fistulas and internal fistulas are needed to define the potential and the limitations of these novel therapeutic approaches.     

Efficacy,tolerability, and predictors of response to infliximab therapy for Crohn's disease: A large single centre experience

BackgroundInfliximab is licenced for use in Crohn's disease (CD). Trial data demonstrate that infliximab is effective for inducing remission of active CD, healing fistulising CD, and preventing relapse once in remission. However, long-term data regarding efficacy, safety, and predictors of response are still emerging.AimTo examine these issues in a large cohort of patients who received infliximab for CD.MethodsA retrospective analysis of prospectively collected data was performed for 210 patients receiving infliximab for luminal or fistulising CD. Response to infliximab induction therapy, and sustained clinical benefit, were assessed by a decrease in Harvey–Bradshaw Index (HBI) of ≥2 points. Remission was defined as an HBI ≤ 4. Physician's global assessment was used where HBI could not be obtained. Demographic and disease factors that may predict response to therapy were analysed by Kaplan–Meier plots and univariate and multivariate analyses.ResultsOverall, 173 (82.4%) patients responded to infliximab induction, with 114 (65.9%) achieving sustained clinical benefit. Almost 40% of the study cohort had an HBI ≤ 4, indicating remission, at last point of follow-up (median 24 months). Concomitant immunosuppression predicted sustained clinical benefit in the first 6 months of therapy (P = 0.03). An inflammatory disease phenotype (P = 0.04 univariate analysis, P = 0.03 Kaplan Meier analysis) and male gender (P = 0.03) also predicted sustained clinical benefit. Episodic therapy was associated with an increased likelihood of secondary non-response. Adverse events, including malignancies, were few.ConclusionIn this single centre study, infliximab was efficacious and well-tolerated in CD.     

Costs of adalimumab versus infliximab as first-line biological therapy for luminal Crohn's disease

Background and aimsRandomised controlled trials demonstrate that the anti-tumour necrosis factor-α (anti-TNFα) therapies infliximab and adalimumab are effective in inducing remission and preventing relapse of Crohn's disease (CD). As few studies have compared costs and efficacy of these two drugs directly, we examined this issue.MethodsData were collected for patients receiving either drug as first-line anti-TNFα for CD. Patients were matched as closely as possible on age, gender, weight, height, and date of commencement of therapy. Response to induction therapy was assessed at 12 weeks, and sustained clinical benefit at last point of follow-up. Resource data were collected for all patients until study end, with National Health Services reference costs applied to calculate the total cost per patient with adalimumab compared with infliximab.ResultsThirty-six patients had been treated with adalimumab as first-line anti-TNFα since 2010. We matched an identical number of infliximab patients. Demographic data were similar between the two groups. Costs were significantly lower with adalimumab (£6692.95 less per patient (95% confidence interval £1816.61–£11569.29)), which was largely driven by the drug costs and drug administration costs associated with infliximab. Twenty-nine (80.6%) patients responded to induction therapy with both drugs, and 22 (61.1%) achieved glucocorticosteroid-free sustained clinical benefit with either drug at last point of follow-up.ConclusionsCosts of infliximab used as first-line anti-TNFα therapy are greater, which may have implications for selection. Clinical outcomes appeared comparable, although power to detect a statistically significant difference would be limited.     

Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease

OBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNF have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CD patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease.     

Medical therapy for Crohn's disease: top-down or step-up?

The emergency of effective biological therapy in the treatment of Crohn's disease (CD) has led to a clinical debate about 'step-up versus top-down strategy'. Step-up refers to the classic therapeutic approach, namely progressive intensification of treatment as disease severity increases. Top-down refers to the early introduction, in all CD patients, of intensive therapies, including biological agents and immunosuppressive drugs, with the aim of avoiding complications and improving quality of life, starting from the assumption that these drugs may interfere with the natural history of the disease. Very recently the Belgian IBD research group together with the Gut Club of North Holland designed 'the Step Up versus Top Down Trial'. Combination of infliximab with immunosuppressives at onset was better than the current standard approach in terms of both induction and maintenance of remission. However, several observations still limit the use of infliximab as first-line treatment in adult CD patients. In particular, the epidemiological observation that over 50% of CD patients have a mild disease over time and will never require aggressive therapies is against the indiscriminate use of top-down strategy. Lack of markers able to identify high-risk patients, discussions about long-term safety and the high costs of infliximab are further factors supporting a more careful approach to the management of CD.     

Review of local injection of anti-TNF for perianal fistulising Crohn’s disease

Background

Perianal fistulising Crohn’s disease (PFCD) affects a third of Crohn’s disease patients and represents a disabling phenotype with poor outcome. The anti-tumour necrosis factor alpha (TNF) therapies have been shown to maintain clinical remission in a third of patients after 1 year of treatment. Maintenance therapy with systematic administration schedules confers greatest benefit, but exposes patients to risks/side effects of continued systemic use and led to consideration of local drug delivery (first described in 2000). In this review, we analyse all published articles on local anti-TNF therapy in the treatment of PFCD.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to systematically search Medline and Embase using the medical subject headings ‘fistula’, ‘anus’, ‘Crohn disease’, ‘infliximab’ and ‘adalimumab’. This was combined with free text searches, e.g. ‘local injection’ and ‘Crohn’s perianal disease’. Studies/abstracts describing local injection treatment with anti-TNF were included in this review.

Results

Six pilot studies including a total of 92 patients were included in this review. Outcomes reported were mostly clinical and included ‘complete/partial response’ to therapy and short-term results varied between 40 and 100%. There were no significant adverse events and the local injections were well tolerated.

Conclusions

There is paucity of data assessing this treatment modality. Local anti-TNF therapy appears safe, but outcome reporting is heterogeneous, subjective and long-term data are unavailable. Our review suggests a potential role may be in those in whom systemic treatment is contraindicated and calls for standardised reporting of outcomes in this field to enable better data interpretation.

     

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease: Case series and review of literature

Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-limumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients(75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.     

Treatment of perianal fistulas in Crohn's disease by local injection of antibody to TNF-alpha accounts for a favourable clinical response in selected cases: a pilot study

OBJECTIVE: Intravenously administered infliximab, a monoclonal antibody directed against tumor necrosis factor-alpha, has been proven to be efficacious in the treatment of fistulas in patients with Crohn's disease. It has recently been suggested that local injections of infliximab might be beneficial as well. The aim of this study was to assess whether infliximab could play an effective role in the local treatment of perianal fistulas in Crohn's disease. MATERIAL AND METHODS: Local infliximab injections were administered to 11 patients suffering from Crohn's disease complicated by perianal disease. Eligible subjects included Crohn's disease patients with single or multiple draining fistulas, regardless of status of luminal disease at baseline. Patients, however, were excluded from the study if they had perianal or rectal complications, such as abscesses or proctitis or if they had previously been treated with infliximab. Twenty-milligram doses of infliximab were injected along the fistula tract and around both orifices at baseline and then every 4 weeks for up to 16 weeks or until complete cessation of drainage. No further doses were administered to patients who did not respond after three injections. Efficacy was measured in terms of response (a reduction in fistula drainage of 50% or more) and remission (complete cessation of fistula drainage for at least 4 weeks). Time to loss of response and health-related quality of life were also evaluated. RESULTS: Overall, 8/11 patients (72.7%) responded to the therapy and 4/11 (36.4%) reached remission, whereas 3/11 patients (27.2%) showed no response. Response or remission was very much dependent on the location of the fistulas, and time to loss of response was generally longer for patients who reached remission compared to patients in response. Changes in health-related quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ), also reflected response or remission, with more marked improvements associated with remission. After a mean 10.5 months' follow-up (range 7-18 months), 6/11 patients (54.5%) are in response and 4/11 patients (36.4%) are in remission. No adverse events have been observed in this cohort of patients. CONCLUSIONS: Local injections of infliximab along the fistula tract seem to be an effective and safe treatment of perianal fistulas in Crohn's disease. However, further controlled clinical investigations are warranted.     

Infliximab vs adalimumab: Points to consider when selecting anti-tumor necrosis factor agents in pediatric patients with Crohn’s disease

Biologic agents with various mechanisms against Crohn’s disease (CD) have been released and are widely used in clinical practice. However, two anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADL), are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently. Therefore, in pediatric CD, the choice of biologic agents should be made more carefully to achieve the therapeutic goal. There are currently no head-to-head trials of biologic agents in pediatric or adult CD. There is a lack of accumulated data for pediatric CD, which requires the extrapolation of adult data for the positioning of biologics in pediatric CD. From a pharmacokinetic point of view, IFX is more advantageous than ADL when the inflammatory burden is high, and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase. Additionally, we reviewed the safety profile, immunogenicity, preference, and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD. Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents. In addition, factors such as the efficacy of induction and maintenance of remission, safety profile, immunogenicity, patient preference, and compliance play an important role in evaluating and selecting treatment options.     

Which patients with inflammatory bowel disease should receive combination therapy?

Traditionally, patients with inflammatory bowel disease underwent ‘step-up’ therapy to induce a clinical remission. However, when step-up treatment is used, the more efficacious anti-TNF agents are reserved for patients unable to achieve remission with immune suppressants (IS). Several pivotal trials have demonstrated the superiority of early combination therapy of IS and anti-TNF to ‘step-up’ therapy and azathioprine or infliximab monotherapy. Concerns about treatment cost and adverse events of combination therapy have precluded widespread adoption of early combination therapy. Recent studies have demonstrated that combination treatment followed by withdrawal of IS or infliximab was not associated with an increased rate of relapse. Providers must include the benefits and risks of combination therapy in shared decision-making discussions with patients about to start treatment. Improved diagnostic and prognostic tests in the future are likely to help providers select the ideal patient for combination therapy.     

Managing complicated Crohn's disease in children and adolescents

The natural history of Crohn's disease is characterized by recurrent exacerbations. A small, but significant, number of pediatric patients with Crohn's disease are resistant to standard medical therapies. The goal of therapy in pediatric patients is not only to achieve and maintain clinical remission, but also to promote growth, development and improve quality of life. All of this needs to be achieved within a relatively short window of opportunity, before growth and development deficiencies become permanent. The standard therapy for pediatric patients with Crohn's disease consists of 5-aminosalicylic-acid compounds, antibiotics and enteral nutrition. Enteral nutrition has an excellent adverse-effect profile and, in addition to its therapeutic effect, positively impacts growth and nutritional status. Immunomodulating medications, such as azathioprine, 6-mercaptopurine and methotrexate, are frequently used to maintain remission, and to treat corticosteroid-dependent and perianal disease. Recently, biologic treatment with the anti-tumor-necrosis-factor-alpha antibody infliximab has dramatically changed the therapeutic approach. The long-term safety of this therapy still needs to be established. Limited data are available on other biologic therapies, which, at this point in time, are considered experimental and are only available through clinical trials.     

Safe use of infliximab for the treatment of severe perianal Crohn’s disease after diagnosis and treatment of lymphoma

Inflammatory bowel disease is associated with an increased likelihood of developing lymphoma. However, it is still controversial if this risk may be attributed to the disease itself or rather represents an effect of immunosuppressive treatment. Although tumor necrosis factor alpha (TNFα) is a key cytokine for cancer immunosurveillance, the potential relationship between anti-TNFα agents and the pathogenesis of lymphoproliferative disorders remains unclear. Here, we describe the case of a patient with severe perianal Crohn’s disease, treated with infliximab monotherapy, whose unusual presentation with acute groin pain required surgical intervention and led to the diagnosis of diffuse large B-cell lymphoma. However, 10 months after this episode, treatment with infliximab was restarted because the patient continued with refractory and disabling perianal disease. Currently, with a follow-up of 36 months, under infliximab 10 mg/kg every 4 weeks, he maintains mild perianal Crohn’s disease and persists in sustained clinical and imaging remission of the lymphoproliferative disorder.     

Optimized timing of using infliximab in perianal fistulizing Crohn's disease

Infliximab(IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease(CD), promote mucosal healing and reduce complications,hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission.There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents.Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging.Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.     

Update on the Management of Ulcerative Colitis

The treatment options for inflammatory bowel disease have expanded with the introduction of biological therapies. Recently published controlled clinical trials were searched and those that impact the clinical management of ulcerative colitis (UC) are discussed in this review. In the management of mild to moderate UC, mesalamine still remains the first choice of drug. The newly developed once daily formulations have shown equal efficacy to divided doses and possibly portend better compliance owing to a simplified regimen. In outpatients with moderate to severe UC, recent data indicate that infliximab induced and maintained remission leads to decreased colectomy rates and fewer hospitalizations. An alternative anti-tumor necrosis factor (TNF) agent, adalimumab, was also recently shown to be effective for induction of remission in moderate to severe UC. The use of immunosuppressives, such as azathioprine and mercaptopurine, is associated with decreased colectomy rates and thioguanine was shown to be effective in maintaining clinical remission in those who are intolerant to azathioprine/mercaptopurine. In hospitalized patients with steroid resistant severe UC, infliximab and tacrolimus may be alternatives to cyclosporine in those who are otherwise candidates for colectomy. Adequate long-term maintenance therapy with immunosuppressives or anti-TNF therapy is required after rescue therapy for a sustained benefit. Future research is needed to position the available anti-TNF agents and combined immunosuppressive therapy in the treatment of UC to achieve and maintain steroid free remission.     

Perioperative adjuvant therapy with infliximab in complicated anal crohn’s disease

PURPOSE: Infliximab may represent an adjuvant to surgical therapy in patients with severe anal Crohn's disease as it has been shown to affect rapid remissions in a proportion of cases. PATIENTS AND METHODS: Nineteen patients underwent infliximab therapy 5 mg/kg perioperatively to scheduled anal reconstructive surgery for complicated fistulising anal Crohn's disease. RESULTS: One adverse event was recorded (generalised exanthema with subsequent resolution). Eight patients showed complete clinical remission refusing further surgery. One of the eight relapsed during follow-up and was continued on infliximab. Surgery consisted of advancement flaps. It was successful at first attempt in nine of the remaining 11 patients (82%). Operative fistula closure remained unsuccessful in two patients. Overall, 16 of 19 patients (84%) with advanced anal Crohn's disease had a favourable outcome. CONCLUSION: The use of infliximab as adjuvant to surgery in this series of patients with complicated anal Crohn's disease was safe. Although the data is uncontrolled a positive effect of infliximab on the outcome of surgery may be postulated since our results compare favourably with other studies.     

Long-term efficacy of adalimumab in Paediatric Crohn's disease patients naïve to other anti-TNF therapies

IntroductionAdalimumab is a fully-humanized anti-TNF a antibody that has showed its efficacy in Crohn’s disease (CD) adult patients. Its less immunogenic composition seems to be an advantage compared to previous anti-TNF α, mainly infliximab. Good response to adalimumab has been reported in patients naïve to infliximab, in those in whom infliximab has shown no efficacy and in those intolerant or who have lost previous response to it. Adalimumab has shown also its efficacy as a second-line anti-TNF α in small series of paediatric CD but data regarding its use in children naïve to infliximab are scarce.AimTo report our experience with adalimumab as first line anti-TNF α treatment in paediatric CD.Patients and methodsFour CD paediatric patients (2 boys) previously naïve to infliximab have received adalimumab. Mean age at diagnosis: 13 years, 4 months. Adalimumab was initiated in our patients soon after diagnosis (mean time from diagnosis: 8.5 months, range: 1 month 15days–14 months) at decreasing loading doses (160mg and 80mg two weeks after) and then 40 mg subsequently every two weeks.ResultsThe four patients entered in remission after the first dose of adalimumab (mean previous PCDAI: 35, mean PCDAI after first dose: 3.6). No adverse effects were registered. Azathioprine was stopped after 4 months of combination therapy, without loss of efficacy or adverse reactions attributable to immunogenicity. All the 4 patients have remained in remission on adalimumab monotherapy for a mean follow-up of 17 months (range 9–20 months).ConclusionAdalimumab has shown its efficacy in our paediatric CD patients naïve to other anti-TNF α drugs. Early introduction of anti-TNF α antibodies in these patients could help to a better control of the disease. Its less immunogenicity and the possibility of a home-based administration are advantages when compared to other parenteral anti-TNF treatments. Change to monotherapy after prior successful combination therapy with azathioprine and adalimumab is a safe strategy that can help to minimize possible risks of intensive immunomodulation.