Adalimumab In Crohn's Disease Research Articles

Adalimumab for Crohn disease: does more mean better?

Adalimumab for Crohn disease: does more mean better?

Adalimumab for induction of remission in patients with Crohn's disease: a systematic review and meta-analysis

PurposeA large number of people with Crohn's disease (CD) fail to recover from conventional therapy or biological therapy. Some studies showed that adalimumab (ADA) may be an effective alternative therapy for these patients. The aim of this study was to evaluate the efficacy and safety of ADA in inducing CD remission.MethodsWe performed search of Pubmed/MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, and several other databases. Randomized controlled trials (RCTs) comparing any dose of ADA with controls (placebo or active) in participants with active CD were included. The primary outcome was the failure to achieve clinical response/remission at 4 weeks. Several subgroup and sensitivity analyses were performed. Review Manager Software v5.3 was used.ResultsFour RCTs were included (n = 919), in which 553 participants received ADA and 366 participants received placebo. A meta-analysis of four studies showed that at 4 weeks, there were more people in the ADA group with clinical response/remission or symptom improvement compared with the placebo group. The rates of side effects, serious side effects, and study withdrawals due to side effects were lower in ADA participants than placebo ones.ConclusionThis meta-analysis shows that ADA is superior to placebo in induction of clinical response/remission of CD patients, but no firm conclusions can be drawn on the safety of ADA in CD due to the low number of events.Graphical

The Effect of Adalimumab Treatment on Linear Growth in Children With Crohn Disease: A Post-hoc Analysis of the PAILOT Randomized Control Trial.

Growth impairment is common in children with Crohn disease (CD). We aimed to assess the effect of adalimumab (ADL) treatment on linear growth in children with CD in a post-hoc analysis of the Pediatric Crohn's Disease AdalImumab Level-based Optimization Treatment randomized controlled trial. Children 6 to 17 years who responded to ADL induction were assessed consecutively for anthropometric parameters. Associations of these parameters with disease characteristics and disease activity were analyzed. Overall, 66 patients completed 72 weeks of follow-up (25% girls, mean age of 15.6 ± 2.5 years). Median (interquartile range [IQR]) height z score improved from -0.6 (-1.6-0.15) at baseline to -0.33 (-1.3-0.5) at week 72 (P = 0.005) with lesser improvement in patients with perianal disease. Similar effect was noted in children with growth potential (boys younger than 16 years, girls younger than 14 years). Median (IQR) height velocity standard deviation was -0.32 (-1.5-0.8) at week 26, and +0.11 (-1.1-1.3) at week 72. Median weight z score increased from -0.54 (-1.2-0.15) to -0.1 (-0.9-0.6), P < 0.001 and body mass index from -0.4 (-1.0-0.5) to 0.0 (-0.8-0.9), P = 0.005. Pediatric CD activity index and erythrocyte sedimentation rate at week 4 correlated negatively with height z score changes (P = 0.043 and P = 0.048, respectively), whereas sustained clinical and biologic remission (week 4-72) were positively associated with changes in height z scores. Significant improvement in linear growth was predicted by lower pediatric CD activity index and erythrocyte sedimentation rate at the end of induction and sustained clinical remission (P = 0.05) and sustained normal C-reactive protein (P = 0.001) at all visits. In children with moderate-to-severe CD, ADL treatment had a significant effect on linear growth, with normalization of weight and body mass index (clinicaltrials.gov no: NCT02256462).

Adalimumab for induction of remission in Crohn's disease.

Adalimumab is an IgG1 monoclonal antibody that targets and blocks tumor necrosis factor-alpha, a pro-inflammatory cytokine involved in the pathogenesis of Crohn's disease (CD). A significant proportion of people with CD fail conventional therapy or therapy with biologics or develop significant adverse events. Adalimumab may be an effective alternative for these individuals. The objectives of this review were to assess the efficacy and safety of adalimumab for the induction of remission in CD. We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, ClinicalTrials.Gov and the World Health Organization trial registry (ICTRP) from inception to 16 April 2019. References and conference abstracts were searched to identify additional studies. Randomized controlled trials (RCTs) comparing any dose of adalimumab to placebo or an active comparator in participants with active CD were included. Two authors independently screened studies, extracted data and assessed bias using the Cochrane 'Risk of bias' tool. The primary outcome was the failure to achieve clinical remission, as defined by the original studies. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than 150 points. Secondary outcomes included failure to achieve clinical response (defined as a decrease in CDAI of > 100 points or > 70 points from baseline), failure to achieve endoscopic remission and response, failure to achieve histological remission and response, failure to achieve steroid withdrawal, adverse events (AEs) and serious adverse events (SAEs), withdrawal from study due to AEs and quality of life measured by a validated instrument. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes. Data were pooled for analysis if the participants, interventions, outcomes and time frame were similar. Data were analyzed on an intention-to-treat basis. The overall certainty of the evidence was assessed using GRADE. Three placebo-controlled RCTs (714 adult participants) were included. The participants had moderate to severely active CD (CDAI 220 to 450). Two studies were rated as at low risk of bias and one study was rated as at unclear risk of bias. Seventy-six per cent (342/451) of adalimumab participants failed to achieve clinical remission at four weeks compared to 91% (240/263) of placebo participants (RR 0.85, 95% CI 0.79 to 0.90; high-certainty evidence). Forty-four per cent (197/451) of adalimumab participants compared to 66% (173/263) of placebo participants failed to achieve a 70-point clinical response at four weeks (RR 0.68, 95% CI 0.59 to 0.79; high-certainty evidence). At four weeks, 57% (257/451) of adalimumab participants failed to achieve a 100-point clinical response compared to 76% (199/263) of placebo participants (RR 0.77, 95% CI 0.69 to 0.86; high-certainty evidence). Sixty-two per cent (165/268) of adalimumab participants experienced an AE compared to 72% (188/263) of participants in the placebo group (RR 0.90, 95% CI 0.74 to 1.09; moderate-certainty evidence). Two percent (6/268) of adalimumab participants experienced a SAE compared to 5% (13/263) of participants in the placebo group (RR 0.44, 95% CI 0.17 to 1.15; low-certainty evidence). Lastly, 1% (3/268) of adalimumab participants withdrew due to AEs compared to 3% (8/268) of participants in the placebo group (RR 0.38, 95% CI 0.11 to 1.30; low-certainty evidence). Commonly reported adverse events included injection site reactions, abdominal pain, fatigue, worsening CD and nausea. Quality of life data did not allow for meta-analysis. Three studies reported better quality of life at four weeks with adalimumab (measured with either Inflammatory Bowel Disease Questionnaire or Short-Form 36; moderate-certainty evidence). Endoscopic remission and response, histologic remission and response, and steroid withdrawal were not reported in the included studies. High-certainty evidence suggests that adalimumab is superior to placebo for induction of clinical remission and clinical response in people with moderate to severely active CD. Although the rates of AEs, SAEs and withdrawals due to AEs were lower in adalimumab participants compared to placebo, we are uncertain about the effect of adalimumab on AEs due to the low number of events. Therefore, no firm conclusions can be drawn regarding the safety of adalimumab in CD. Futher studies are required to look at the long-term effectiveness and safety of using adalimumab in participants with CD.

Infliximab and adalimumab concentrations and anti-drug antibodies in inflammatory bowel disease control using New Zealand assays.

Therapeutic drug monitoring of anti-tumour necrosis factor (TNF) drugs and anti-drug antibodies (ADA) is now recommended in the treatment of inflammatory bowel disease. However, assay types and drug concentration thresholds are still debated. To correlate inflammatory bowel disease activity in a New Zealand cohort with trough concentrations of infliximab and adalimumab, and ADA using locally developed competitive-binding enzyme-linked immunosorbent assays (ELISA) to establish threshold concentrations. Patients with ulcerative colitis (UC) and Crohn disease (CD) from Christchurch and Dunedin on anti-TNF drugs >12 weeks were enrolled. Trough blood samples were assayed for drug and ADA concentrations. Other data included quality of life, blood count, C-reactive protein, albumin, renal function and disease activity indices. Of 103 patients, 53 were on infliximab (36 CD, 15 UC and 2 unclassified) and 50 adalimumab (48 CD and 2 UC). Median (range) infliximab and adalimumab concentrations were 10.5 (0-41) and 9.61 mg/L (0-30). CD remission, Crohn Disease Activity Index <150, correlated with infliximab and adalimumab concentration in CD (infliximab, P = 0.03; adalimumab, P = 0.04), with too few UC patients for analysis. Receiver operator curve analysis suggested a threshold value of 5.1 mg/L for distinguishing active disease from remission for infliximab and 7.3 mg/L for adalimumab in CD. Of 13 patients with infliximab <2 mg/L, 10 were ADA positive by homogeneous mobility shift assay (HMSA), including five with neutralising antibodies using ELISA. Of six with adalimumab <2 mg/L, three were ADA positive using HMSA, including one with neutralising antibodies. Using the New Zealand ELISA assay, threshold concentrations of 5 mg/L for infliximab and 7 mg/L for adalimumab are suggested to aid dosing decisions, consistent with results internationally. Both neutralising (ELISA) and non-neutralising ADA (HMSA) are associated with low drug concentrations.

Anti-NMDAR encephalitis in a patient with Crohn disease receiving adalimumab.

Anti–tumor necrosis factor alpha (TNF-α) therapies have been a significant advance in the treatment of autoimmune and rheumatologic diseases. Early preclinical and clinical studies of anti–TNF-α therapies emphasized infection and malignancy as serious adverse events associated with these agents.1 However, subsequent clinical experience has increasingly recognized a rare and seemingly paradoxical risk of autoimmunity with agents targeting the TNF-α pathway, most notably psoriatic eruptions,2 but also autoimmune processes associated with autoantibody production, including systemic vasculitis and lupus erythematosus.3,4 The development of neurologic diseases in association with anti–TNF-α therapy has been documented in case series and small prospective studies,5 with the most commonly reported associations being demyelinating diseases of the CNS and peripheral nervous systems. Here, we report a patient who developed anti–NMDA receptor (NMDAR) encephalitis while being treated with adalimumab for Crohn disease.

P496 Successful dose de-escalation to adalimumab 40mg every three weeks in patients with Crohn's disease

Background: Data on de-escalation of adalimumab (ADM) therapy in patients with Crohn's disease (CD) in clinical remission are scarce. However, dose de-escalation may not only have beneficial economic consequences, it might also decrease adverse events (AE). In this retrospective study, the outcome of dose de-escalation to ADM 40 mg every three weeks (ETW) in patients with CD was studied. Methods: Out of 703 patients treated with ADM for CD in a tertiary referral center, we selected all patients who had received maintenance therapy with ADM 40 mg ETW with serum levels (SL) available before and after dose de-escalation. A sex- and age-matched control group consisted of patients continuing ADM 40mg EOW. ADM SL were measured using RIDASCREEN® In addition, patient reported outcome (PRO2), C-reactive protein (CRP) and serum albumin were collected. Other baseline variables included disease behavior, disease location, smoking behavior, concomitant therapy, bodyweight, and body mass index. ROC curve analyses were performed to define cut off values for continuous variables. Mann-Whitney U, Wilcoxon Signed Rank test, and Cox regression were performed using SPSS 23.0 Results: We identified 40 patients (11 male, median age 37 years) who dose de-escalated to ADM 40 mg ETW for ADM-related AE (n=1), ADM SL >7μg/mL (n=8), or both (n=31). Compared to the control population, ADM SL dropped significantly within four months, but without associated clinical or biochemical changes. Table 1. Evolution of clinical and biochemical markers after dose de-escalation. During a median follow-up of 24 months, 65% of patients maintained clinical response, but 35% needed dose escalation back to ADM 40mg EOW because of clinical relapse (n=8), ADM SL dropping to <4μg/mL (n=2), or both (n=4). CRP <3.5mg/L at dose de-escalation was independently associated with dose escalation free survival [Odds ratio 6.28 (95% CI 1.83–21.59), p=0.004]. We could not define a minimal ADM SL to consider or maintain dose de-escalation. In 53% of 32 patients with AE dose de-escalation was associated with a complete disappearance of AE after a median of 4 months (8/15 skin manifestation, 3/7 arthralgia, 5/7 frequent infectious episodes). Conclusions: In this retrospective cohort analysis, 65% of patients were able to continue ADM therapy at a dose of 40 mg ETW for a median of 24 months. In half of the patients who experienced ADM related AE at baseline, the AE disappeared completely. Regardless of ADM serum levels, disease remission should be objectively assessed prior to dose de-escalation, since an elevated baseline CRP predicted clinical relapse and dose escalation back to 40mg EOW.

Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.

IMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported. Patients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015. Of 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified. Efficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials.

Tu1924 Comparative Effectiveness of Infliximab and Adalimumab in Crohn's Disease and Ulcerative Colitis

Tu1924 Comparative Effectiveness of Infliximab and Adalimumab in Crohn's Disease and Ulcerative Colitis

Long-Term Safety of Adalimumab in Clinical Trials in Adult Patients With Crohnʼs Disease or Ulcerative Colitis

Introduction: Adalimumab (ADA) is a fully human anti-tumor necrosis factor (TNF) monoclonal antibody used for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) in patients who have inadequately responded to conventional therapies. Safety from ongoing ADA trials continues to be collected, allowing assessment of long-term safety as the number of patients and the amount of exposure to ADA increase. The aim is to provide an update on the long-term safety profile of ADA in CD and UC patients. Methods: Safety data were evaluated for adult patients with CD or UC treated with ADA in randomized, placebo-controlled, phase 3 and 3b trials as well as their open-label extension studies. Treatmentemergent adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities, version 17.1(2014), and collected from the first dose to up to 70 days after the last dose or through the cutoff date of 31 Dec 2014. AE rates were assessed as events (E) per 100 patient-years (PYs) of exposure to ADA. Results: As of 31 Dec 2014, the ADA clinical safety database contained data for 3689 CD patients and 1789 UC patients, representing 4178.7 and 3371.9 PYs of ADA exposure, respectively. Overall, AE, SAE, and malignancy rates per PYs exposure were similar between the prior and the most recent data cutoffs for each disease state (Table). The type of infections in the Opportunistic infections (excluding TB) category changed in 2014 resulting in an apparent decreased rate (Table). Conclusion: ADA continues to be well tolerated in patients with moderately to severely active CD and UC. No new safety signals were identified with prolonged ADA use in these patient groups.Table 1: Safety Profile of Adalimumab in Adult CD and UC Patients

Sa1131 PYRAMID Registry: An Observational Study of Adalimumab in Crohn's Disease: Results at Year 6

Background: This study evaluated the long-term safety of adalimumab (ADA), as used in routine clinical practice, for up to 6 years in patients with moderately to severely active Crohn's disease (CD) enrolled in the global observational registry PYRAMID. Methods: All patients entering the multi-centre, non-interventional registry PYRAMID were to be followed for up to 6 years. Adverse events (AEs) were collected from the first dose to up to 70 days after the last dose of ADA or through the cutoff of 1 December 2013. AE rates are reported as per 100 patient-years (PY). Results: A total of 5061 patients (57.1% female, mean age 37.8 years, median duration of CD 8.2 years) have enrolled in PYRAMID, totaling 13924.3 PY of ADA exposure, excluding prior exposure in CD ADA clinical trials. As of 01 Dec 2013, 2885 patients (57%) were still participating and 297 patients (5.9%) had at least 6 years of ADA exposure. A total of 2600 patients (51%) received biologic therapy prior to enrollment (98.3% infliximab, 5.6% certolizumab, 1.4% natalizumab, 0.5% other). During the study, concomitant corticosteroids (CS), immunosuppressants (IMM), and IMM + CS were used by 29.4%, 35.6%, and 11.6% of patients, respectively. A total of 682 patients (4.9/100 PY) experienced serious infections, of which 265 patients (5.1/100 PY) were on combination therapy with IMM and 417 patients (4.8/100 PY) were on ADA monotherapy. A total of 104 patients (0.7/100 PY) experienced any malignancy, of which 50% had received combination therapy with IMM. Thirty-eight treatment-emergent deaths (0.3/100 PY) were reported, of which 7 were considered possibly related to ADA. Overall, ADA-exposed patients did not have an increased mortality versus the general population. The Table shows an overview of exposure-adjusted registry treatment-emergent AEs for years 3, 5, and 6. Conclusion: After up to 6 years of observation, long-term ADA exposure continued to be welltolerated in patients with moderately to severely active CD. No new safety signals were identified. AE rates remained stable over time. Table. Cumulative incidence of treatment-emergent adverse events (AEs) excluding prior exposure in other CD ADA trials

Sa1132 A Retrospective Cohort Study of Rates of Clostridium difficile Infection in Moderate-to-Severe Inflammatory Bowel Disease Patients Treated With Vedolizumab vs. Infliximab at a Canadian Tertiary Hospital

Background: This study evaluated the long-term safety of adalimumab (ADA), as used in routine clinical practice, for up to 6 years in patients with moderately to severely active Crohn's disease (CD) enrolled in the global observational registry PYRAMID. Methods: All patients entering the multi-centre, non-interventional registry PYRAMID were to be followed for up to 6 years. Adverse events (AEs) were collected from the first dose to up to 70 days after the last dose of ADA or through the cutoff of 1 December 2013. AE rates are reported as per 100 patient-years (PY). Results: A total of 5061 patients (57.1% female, mean age 37.8 years, median duration of CD 8.2 years) have enrolled in PYRAMID, totaling 13924.3 PY of ADA exposure, excluding prior exposure in CD ADA clinical trials. As of 01 Dec 2013, 2885 patients (57%) were still participating and 297 patients (5.9%) had at least 6 years of ADA exposure. A total of 2600 patients (51%) received biologic therapy prior to enrollment (98.3% infliximab, 5.6% certolizumab, 1.4% natalizumab, 0.5% other). During the study, concomitant corticosteroids (CS), immunosuppressants (IMM), and IMM + CS were used by 29.4%, 35.6%, and 11.6% of patients, respectively. A total of 682 patients (4.9/100 PY) experienced serious infections, of which 265 patients (5.1/100 PY) were on combination therapy with IMM and 417 patients (4.8/100 PY) were on ADA monotherapy. A total of 104 patients (0.7/100 PY) experienced any malignancy, of which 50% had received combination therapy with IMM. Thirty-eight treatment-emergent deaths (0.3/100 PY) were reported, of which 7 were considered possibly related to ADA. Overall, ADA-exposed patients did not have an increased mortality versus the general population. The Table shows an overview of exposure-adjusted registry treatment-emergent AEs for years 3, 5, and 6. Conclusion: After up to 6 years of observation, long-term ADA exposure continued to be welltolerated in patients with moderately to severely active CD. No new safety signals were identified. AE rates remained stable over time. Table. Cumulative incidence of treatment-emergent adverse events (AEs) excluding prior exposure in other CD ADA trials

Early Intervention with Adalimumab May Contribute to Favorable Clinical Efficacy in Patients with Crohn's Disease

Background: We evaluated the clinical efficacy of adalimumab (ADA) for Crohn's disease (CD) and analyzed predictive factors for clinical remission and long-term prognosis. Methods: We retrospectively reviewed the medical records of 45 patients treated with ADA for CD at Keio University Hospital between October 2010 and March 2014. Clinical remission was defined as a Harvey-Bradshaw index of ≤4. Results: Twenty-eight of 45 patients (62.2%) achieved clinical remission at week 4. Among these 28 patients, 18 patients (64.3%) maintained clinical remission at week 26, and among these, 16 patients (88.9%) maintained clinical remission at week 52. Absence of a history of bowel resection and absence of prior anti-tumor necrosis factor (anti-TNF) therapy were significant predictive factors for clinical remission at week 4 upon multivariate logistic regression analyses. Younger age and a disease duration of ≤3 years correlated with clinical remission at week 26 upon univariate analyses. Patients without a history of bowel resection showed significantly better long-term prognosis than those with a history of bowel resection (p = 0.01). None of the patients contracted a serious infectious disease. Conclusions: Younger age, shorter duration of disease, being naive to anti-TNF antagonists, and absence of a history of bowel resection were associated with the efficacy of ADA in CD patients.

Efficacy and safety of adalimumab for the Crohn's disease: a systematic review and meta-analysis of published randomized placebo-controlled trials.

The aim of this study was to evaluate the efficacy and safety of adalimumab (ADA) for Crohn's disease. Electronic databases, including PubMed, Embase, the Cochrane Library, and the Science Citation Index, were searched to retrieve relevant trials. We estimated pooled estimates of the odds ratio (OR) and relevant 95% confidence interval (CI) using fixed effects model or random effects model as appropriate. Six randomized placebo-controlled studies met the selection criteria. Short-term clinical response/remission and long-term remission were better in the ADA groups than in the control groups (P < 0.05), both in anti-TNF-naive patients and in subjects who lost their response and/or became intolerant to infliximab (IFX). And ADA was also effective for patients who were previously treated with IFX, and its efficacy in infliximab-exposed patients was probably less than in infliximab-naive patients. In patients with active Crohn's disease (CD), ADA therapy was more effective than placebo for obtaining complete fistula closure. In comparison with placebo, ADA does not increase the risk of serious adverse events. ADA appears to be effective in achieving short-term clinical response/remission, long-term remission, and complete fistula healing in CD, including patients not manageable with IFX, and appears to have a favorable safety profile. A longer duration of follow-up and a larger number of patients are required to better assess the safety profile of ADA in CD.

Su1392 Benefit of Infliximab Re-Introduction After Successive Failure of Infliximab and Adalimumab in Crohn's Disease

Background: Infliximab [IFX] and adalimumab [AD A] are effective in Crohn’s disease [CD] for induction and maintenance therapy. However, high annual rate of discontinuation for loss of response or intolerance may lead to a switch to another anti-tumor necrosis factor agent. Patients with successive failure to IFX and ADA are becoming more frequent. The aim of this study was to assess the efficacy and the tolerance of re-treatment with IFX in CD patients who successively failed IFX and ADA. Methods: A total of 61 patients with CD who recei ved and discontinued successively IFX and ADA, and who were re-exposed to IFX, were identified in four French tertiary centers and retrospectively analyzed. Clinical data, follow-up and outcome were abstracted from medical records. Results: Median treatment duration af ter reintroduction was 16 months, and probability of remaining under IFX was 60% and 51%, respectively, at 12 and 24 months. In all 29 patients discontinued the second IFX treatment due to intolerance [13], primary non-response [8], loss of response [7] or patient’s wish [1]. Remission was achieved in 42% at week 6–8 after IFX re-induction, and was predictive of better long-term response [p = 0.006]. In multivariate analysis, receiving co-immunosuppression in both first and second IFX treatments [p = 0.04] and shorter interval between first and second IFX treatments [p = 0.017] were independently associated with longer duration of second IFX treatment. Conclusion: F or CD patients who successively failed IFX and ADA, reintroducing IFX is feasible and often clinically efficient, particularly in patients who received co-immunosuppression during both first and second IFX treatments.

Comparative Effectiveness of Infliximab and Adalimumab for Crohn's Disease

Antibodies against tumor necrosis factor-α are widely used to treat patients with Crohn's disease (CD). This study compared the effectiveness of infliximab and adalimumab, the 2 most commonly used anti-tumor necrosis factor agents, in patients with CD. We conducted a retrospective cohort study by using U.S. Medicare data from 2006 through 2010. Patients with CD who were new users of infliximab (n = 1459) or adalimumab (n = 871) after January 31, 2007, were included. Patients older than age 85 and those with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis were excluded. The primary outcome measures were disease persistence on therapy at week 26, surgery (including bowel resection, creation of an ostomy, or surgical treatment of a perforation or abscess), and hospitalization for CD. Propensity score-adjusted logistic and Cox regression were used to compute adjusted odds ratios or hazard ratios and 95% confidence intervals (CIs). After 26 weeks of treatment, 49% of patients receiving infliximab remained on drug, compared with 47% of those receiving adalimumab (odds ratio, 0.98; 95% CI, 0.81-1.19). Fewer patients treated with infliximab underwent surgery than those treated with adalimumab, but this difference was not statistically significant (5.5 vs 6.9 surgeries per 100 person-years; hazard ratio, 0.79; 95% CI, 0.60-1.05). Rates of hospitalization did not differ between groups (hazard ratio, 0.88; 95% CI, 0.72-1.07). We observed similar effectiveness of infliximab and adalimumab for CD on the basis of 3 clinically important outcome measures.

Su1264 Re-Induction Regimen in Crohn's Disease Adalimumab Failure or Disease Relapse After a First Adalimumab Course. A Single Centre Experience

Background: Adalimumab (ADA) is a fully human monoclonal antibody targeting TNF-alfa with proven efficacy in the treatment of Crohn’s disease (CD). We evaluate the efficacy of a second new ADA induction regimen. Methods: Forty-six CD patients were treated with a second ADA induction regimen (40 patients with 160/80mg, 6 with 80/40mg) and maintenance with 40mg every other week (22 patients) or weekly (24 patients). Patients were divided into 3 groups: moderate CD relapses [Harvey Bradshaw score (HBI) >8] during ADA maintenance treatment after an initial response were defined as ‘secondary non responders’ (SNR), failures at week 12 of the first induction regimen as ‘primary non responders’ (PNR) and CD recurrences [HBI score >5] within 6 months after the first successful ADA course as ‘early relapses’ (ER). Three of them received azathioprine (AZA) plus ADA. Clinical response or remission were evaluated at week 12 [remission: HBI <4; response: 3-point reduction in the HBI vs baseline]. Results: Of 149 CD patients treated with ADA and followed prospectively, 46 patients [M/F: 24/22; mean age 31.7 years (18 63 years); median disease duration 7 years (0.3 18 years); disease location: 7 ileal, 23 ileo-colonic, 16 colonic; mean HBI at the baseline 11.9 (6 38)] were enrolled. Eighteen patients were SNR (mean first ADA treatment duration: 50 weeks), 14 were PNR (mean first ADA treatment duration:14 weeks) and 14 had an ER (mean first ADA treatment duration:77 weeks). Considering the overall group of patients, at week 12 remission was observed in 24 patients (52.2%), 10 patients (21.7%) had partial response, while 12 patients (26.1%) had no improvement. In the subgroup of SNR, 5 patients (27.8%) regained remission, 5 regained (27.8%) response, while 8 (44.4%) had no response. Seven patients (50.0%) out of the 14 PNR gained remission, 3 patients (21.4%) had a partial response and 4 patients (28.6%) had no response to the second ADA course. The 3 patients treated with ADA plus AZA achieved complete remission around week 24. All of the 14 ER patients responded to the second ADA course: 12 (85.7%) showed new complete remission, 2 patients (14.3%) had partial response. Conclusions: ADA re-induction regimen seems to be effective in patients who lost response during ADA maintenance treatment (SNR). Dose intensification with a new early induction regimen showed efficacy to gain response in PNR. A new induction regimen with ADA seems to be extremely effective to regain remission in patients with ER and previous ADA-response.

P395 Re-induction regimen in Crohn's disease adalimumab failure or disease relapse after a first adalimumab course. A single centre experience

P395 Re-induction regimen in Crohn's disease adalimumab failure or disease relapse after a first adalimumab course. A single centre experience

OP15 Immunosuppressive co-treatment with adalimumab (ADA) may be more effective than ADA monotherapy for maintaining remission in Crohn's disease (CD)

Background: There is clear benefit of combination therapy for infliximab (IFX) with immunosuppressive drugs (IS), whether commenced together, or later, but no data are available for ADA. The aim was to assess whether IS combotherapy (CoT) was more effective than monotherapy for Crohn’s disease (CD) patients treated with ADA, using the semester approach. Methods: Retrospective study of patients with CD (n = 181) treated for at least one year with ADA in Oxford, UK or Liege, Belgium. Treatment periods were divided into 6 month semesters and the treatment failure compared between semesters with or without CoT (thiopurines or methotrexate). ADA failure was defined as dose modification during therapy, drug modification, perineal complications, or surgery for active CD. Results: 569 semesters were studied in 181 patients (Oxford n = 98, Liege 83), including 147 semesters in 45 patients having received CoT during the first semester. More patients in Oxford received CoT than Liege (OR: 4.82, p < 0.0001) and fewer females (OR 0.50, p = 0.01). When considering only patients on CoT during the first semester, treatment failures were less frequent in semesters with IS (20%) compared to semesters without IS (80%; OR 0.30, p = 0.02). This protective effect of the CoT was maintained over time (p = 0.01). When considering all the patients, CoT in the first semester was associated with a lower frequency of treatment failures (34% vs 66%, OR 0.69, p = 0.046) in univariate analysis but not in multivariate analysis. CoT later after induction of ADA was not associated with treatment failures. Female gender (OR 1.68, p = 0.01), previous surgery (OR 1.89, p = 0.001) and active perianal disease (OR 1.57, p = 0.02) were risk factors of failure on multivariate analysis. Although failures were less common in Oxford (OR 0.52, p = 0.001), more failures in Oxford had surgery (OR 8.85, p = 0.001) or perianal complications (OR 3.33, p = 0.01) and fewer had ADA weekly (OR 0.24, p = 0.0003) on multivariate analysis. The overall number of operations and perianal complications did not differ between CoT and ADA monotherapy. Thiopurines appeared more effective than methotrexate for preventing failure (OR 0.35, p = 0.03). The probablility of failure did not increase over the semesters (p = 0.86). Conclusions: When it was given during the first semester, CoT with ADA in CD was associated with fewer semesters with treatment failures (essentially the need for dose escalation or treatment modification, but not the rate of surgery or perianal complications). OP16 Adding ciprofloxacin to adalimumab results in a higher fistula closure rate in perianal fistulizing Crohn’s disease P. Dewint1 *, B. Hansen1, E. Verhey1, B. Oldenburg2, D.W. Hommes3, M. Pierik4, C. Ponsioen5, H. van Dullemen6, M.G. Russel7, A. van Bodegraven8, C.J. van der Woude1, on behalf of ICC (Initative on Crohn’s and Colitis). 1Erasmus Medical Center, Department of Gastroenterology & Hepatology, Rotterdam, Netherlands, 2University Medical Centre Utrecht, Department of Gastroenterology, Utrecht, Netherlands, 3UCLA, Division of Digestive Diseases, Los Angeles, United States, 4Maastricht University Medical Center, Dept of Gastroenterology, Maastricht, Netherlands, 5Academic Medical Center, Gastroenterology and Hepatology, Amsterdam, Netherlands, 6UMC Groningen, Gastroenterology, Groningen, Netherlands, 7Medisch Spectrum Twente, Gastroenterology, Enschede, Netherlands, 8VU University Medical Center, Gastroenterology, Amsterdam, Netherlands

Pneumocystosis in a patient with Crohn's disease treated with combination therapy with adalimumab

Pneumocystis jirovecii pneumonia (PCP) is a potential complication of immunosuppression. Crohn's disease (CD) is an immune granulomatous disorder characterized by transmural inflammation that can affect any part of the gastrointestinal tract. Its treatment is based on steroids and immunosuppressants but in non-responders, biologic compounds such as anti-tumor necrosis factor alpha (TNF) antibodies have been used. Neutralization of TNF causes a decrease in the inflammatory response but increases susceptibility to opportunistic infections such as fungal infections.We report a young male with chronic diarrhea, fever and weight loss who was diagnosed with CD and began conventional treatment with immunosuppressants, but due to lack of response after several weeks, biologic therapy with adalimumab was initiated. Seven weeks later he developed persistent fever and upper respiratory symptoms. After chest CT, bronchoscopy and bronchial lavage, P. jirovecii was identified by silver staining and confirmed by immunofluorescence. To our knowledge this is the second case of pneumocystosis associated with the use of adalimumab in CD and the first reported Mexican case confirmed by microbiological and immunological studies in this setting.