An Open-Label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Prior Loss of Response or Intolerance to Infliximab for Crohn's Disease Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial Adalimumab produces clinical remission and reduces extraintestinal manifestations in Crohn's disease: Results from CARE Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn’s disease who failed prior infliximab therapy Adalimumab in patients with Crohn’s disease – safety and efficacy in an open‐label single centre study Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. Efficacy and safety of adalimumab in Canadian patients with moderate to severe Crohn's disease: results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn's DiseaSe (ACCESS) trial. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Efficacy and safety of short‐term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open‐label, multicentre trial A Pilot Study of Adalimumab in Infliximab-Allergic Patients Adalimumab maintenance therapy for Crohn’s disease with intolerance or lost response to infliximab: an open‐label study
BACKGROUND : We assessed the tolerability and clinical benefit of adalimumab , a human antibody to tumor necrosis factor ( TNF ) , in patients with Crohn 's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab , but who no longer had a sustained response and /or tolerance to infliximab . METHODS : A total of 24 patients with Crohn 's disease who had lost responsiveness or developed intolerance ( acute or delayed infusion reactions ) to infliximab  were enrolled in a 12-wk uncontrolled trial and treated with subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting at week 2 . After week 4 , the dose could be escalated to 40 mg weekly in patients who did not achieve clinical remission , complete fistula closure , and complete steroid withdrawal . Outcome measures included the ability to tolerate adalimumab and clinical remission ( defined as a Crohn 's disease activity index ( CDAI ) score ≤150 points ) and clinical response ( defined as a decrease in the CDAI ) ≥100 points ) in patients who had a baseline CDAI score ≥220 . RESULTS : None of the patients experienced acute or delayed hypersensitivity reactions during treatment with adalimumab ( including 14 who previously experienced treatment-limiting acute hypersensitivity reactions and 6 who previously experienced delayed hypersensitivity reactions with infliximab ) . Of 17 patients with baseline CDAI scores ≥220 : clinical remission occurred at weeks 4 and 12 in 2 ( 12 % ) and 5 ( 29 % ) , respectively ; and clinical response occurred in 7 ( 41 % ) and 10 ( 59 % ) , respectively . Nineteen patients ( 79 % ) escalated their dose during weeks 4–6 . CONCLUSIONS : Adalimumab is well tolerated and appears to be a clinical ly beneficial option for patients with Crohn 's disease who have previously lost their response to , or can not tolerate infliximab Background : Adalimumab induced clinical remission after four weeks in patients with active Crohn ’s disease in the CLASSIC I trial . Objective : To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn ’s disease in a follow-on r and omised controlled trial ( CLASSIC II ) . Methods : In the preceding CLASSIC I trial , 299 patients with moderate to severe Crohn ’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg , or placebo , at weeks 0 and 2 . In all , 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 ( week 4 of CLASSIC I ) and 2 ; 55 patients in remission at both weeks 0 and 4 were re-r and omised to adalimumab 40 mg every other week , 40 mg weekly , or placebo for 56 weeks . Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week . With non-response or flare , these patients could have their dosages increased to 40 mg weekly . Patients in the r and omised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly . The primary end point was maintenance of remission ( CDAI < 150 ) in r and omised patients through week 56 . Results : Of 55 patients r and omised at week 4 , 79 % who received adalimumab 40 mg every other week and 83 % who received 40 mg weekly were in remission at week 56 , v 44 % for placebo ( p<0.05 ) . In all , 204 patients entered the open-label arm . Of these , 93 ( 46 % ) were in clinical remission at week 56 . Adalimumab was generally well-tolerated in all patients . Conclusions : Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn ’s disease naive to anti-TNF treatment Background : Data regarding the effectiveness of anti‐tumor necrosis factor ( TNF ) agents for resolution of extraintestinal manifestations ( EIMs ) are scarce . The CARE study evaluated clinical effectiveness , EIM resolution , and safety of adalimumab in a large pan‐European cohort of patients with moderate to severe Crohn 's disease ( CD ) . Methods : In all , 945 patients with a Harvey – Bradshaw Index ( HBI ) ≥7 enrolled in this multicenter , open‐label phase IIIb trial . Patients received subcutaneous adalimumab , 160/80 mg at weeks 0/2 , then 40 mg every other week . Dose adjustments were allowed for CD‐related concomitant medications ( from week 8) and adalimumab ( from week 12 ) . Clinical endpoints were analyzed through week 20 for all patients , and after stratification by prior infliximab exposure and by reason for discontinuing infliximab ( primary nonresponse [ PNR ] or other ) . Results : The remission rate ( HBI < 5 ) at week 20 was 52 % ( 95 % confidence interval , 49%–55 % ) overall , and was higher for infliximab‐naïve versus infliximab‐exposed patients ( 62 % versus 42 % , P < 0.001 ) . Remission rates were similar for PNR ( 37 % ) and other reasons ( 43 % ; P = 0.278 ) . Of 497 patients with baseline EIMs , 51 % were free of EIM signs and symptoms at week 20 . Serious infectious adverse events were reported in 5 % of patients . Opportunistic infections and malignancies were rare ( ≤1 % ) . There was one case of demyelinating disease , but no occurrences of lupus , tuberculosis , or death . Conclusions : In this large cohort of patients , adalimumab treatment result ed in rates of clinical remission and EIM resolution exceeding 50 % , and substantial rates of effectiveness in patients who had PNR to  infliximab . Adalimumab was well tolerated , with safety consistent with prior reports . ( Inflamm Bowel Dis 2011 BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab  , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug Aliment Pharmacol Ther 2010 ; 32 : 1228–1239 To evaluate the efficacy and safety of adalimumab , a human antitumour necrosis factor‐α antibody , in induction and maintenance of remission in patients with Crohn ’s disease either refractory or intolerant to infliximab in a single centre cohort BACKGROUND Treatment with infliximab , a chimeric monoclonal IgG1 antibody against tumor necrosis factor , can result in the formation of antibodies against infliximab . We evaluated the clinical significance of these antibodies in patients with Crohn 's disease . METHODS In a cohort of 125 consecutive patients with Crohn 's disease who were treated with infliximab infusions  , we evaluated the concentrations of infliximab and of antibodies against infliximab  , clinical data , side effects ( including infusion reactions ) , and the use of concomitant medications before and 4 , 8 , and 12 weeks after each infusion . RESULTS A mean of 3.9 infusions ( range , 1 to 17 ) per patient were administered over a mean period of 10 months . Antibodies against infliximab  were detected in 61 percent of patients . The presence of concentrations of 8.0 microg per milliliter or greater before an infusion predicted a shorter duration of response ( 35 days , as compared with 71 days among patients with concentrations of less than 8.0 microg per milliliter ; P<0.001 ) and a higher risk of infusion reactions ( relative risk , 2.40 ; 95 percent confidence interval , 1.65 to 3.66 ; P<0.001 ) .  Infliximab concentrations were significantly lower at four weeks among patients who had had an infusion reaction than among patients who had never had an infusion reaction ( median , 1.2 vs. 14.1 microg per milliliter ; P<0.001 ) . Patients who had infusion reactions had a median duration of clinical response of 38.5 days , as compared with 65 days among patients who did not have an infusion reaction ( P<0.001 ) . Concomitant immunosuppressive therapy was predictive of low titers of antibodies against infliximab  ( P<0.001 ) and high concentrations of  infliximab  four weeks after an infusion ( P<0.001 ) . CONCLUSIONS The development of antibodies against infliximab is associated with an increased risk of infusion reactions and a reduced duration of response to treatment . Concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response OBJECTIVE To evaluate open-label adalimumab therapy for clinical effectiveness , fistula healing , patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn 's disease ( CD ) who were either naive to or previously exposed to antitumour necrosis factor ( anti-TNF ) therapy . METHODS Patients with moderate to severe CD ( CD activity index [ CDAI ] score of greater than 220 , or Harvey-Bradshaw index [ HBI ] of 7 or greater ) were eligible . Patients received open-label adalimumab as induction ( 160 mg and 80 mg subcutaneously [ sc ] ) at weeks 0 and 2 , respectively and maintenance ( 40 mg sc every other week ) therapy . At or after eight weeks , patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly . Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada . RESULTS Of the 304 patients enrolled , 160 were infliximab experienced , while 144 were anti-TNF naive .  HBI remission ( HBI score of 4 or lower ) at week 24 was achieved by 53 % of anti-TNF-naive and 36 % of infliximab-experienced patients ( P<0.01 ; P<0.001 for both groups for all visits versus baseline ) . Fistula healing rates at week 12 were 48 % for anti-TNF-naive patients , and 26 % for infliximab-experienced patients . At week 24 , fistula healing rates were significantly greater for the anti-TNF-naive group ( 60 % versus 28 % ; P<0.01 ) . Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients . Serious infections occurred in 2 % of patients . CONCLUSIONS Adalimumab therapy induced and sustained steroidfree remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD . Clinical ly meaningful rates of fistula healing were also observed . Improvements in patient-reported outcomes were sustained throughout the 24-week study period BACKGROUND & AIMS Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn 's disease ( CD ) . Adalimumab is a human immunoglobulin G1 ( IgG(1 ) ) monoclonal antibody targeting tumor necrosis factor ( TNF ) . A r and omized , double-blind , placebo-controlled , dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD . METHODS A total of 299 patients with moderate to severe CD naive to anti-TNF therapy  were r and omized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg or placebo . The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 ( defined as a Crohn 's Disease Activity Index score < 150 points ) among the 80 mg/40 mg , 160 mg/80 mg , and placebo groups . RESULTS The rates of remission at week 4 in the adalimumab 40 mg/20 mg , 80 mg/40 mg , and 160 mg/80 mg groups were 18 % ( P = .36 ) , 24 % ( P = .06 ) , and 36 % ( P = .001 ) , respectively , and 12 % in the placebo group . Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions , which were more common in adalimumab-treated patients . CONCLUSIONS Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn 's disease naive to anti-TNF therapy . The optimal induction dosing regimen for adalimumab in this study was 160 mg at week 0 followed by 80 mg at week 2 . Adalimumab was well tolerated The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn 's disease The anti-TNF-&agr ; antibody infliximab ( Remicade ) is highly effective in the treatment of Crohn 's disease . A subset of patients experience allergic reactions as a result of antibodies to infliximab ( ATIs ) . The purpose of the current study is to describe the safety and efficacy of adalimumab ( Humira ) in patients previously allergic or intolerant to infliximab . Adalimumab is an anti-TNF-&agr ; agent containing only human peptide sequences . Seven patients have been treated with adalimumab who had experienced immediate- or delayed-hypersensitivity reactions to infliximab and one with infliximab-induced lupus . Except for injection site discomfort , adalimumab was well tolerated without signs or symptoms of allergic reactions . One patient who had previously received pooled human immunoglobulin developed a pruritic rash after each dose of adalimumab . Patients with active disease who had previously experienced a robust response to infliximab responded to adalimumab as reflected by an improvement in Harvey-Bradshaw index and inflammatory markers . Based on these preliminary data , adalimumab may be a safe and effective substitute for  infliximab-allergic patients . Individuals who have been exposed to human antibodies may be sensitized to other human antibodies such as adalimumab Adalimumab is effective in inducing remission in patients with active Crohn ’s disease who had secondary failure to infliximab therapy
The tumor necrosis factor inhibitors infliximab and adalimumab are effective treatments for Crohn 's disease ( CD ) ; however , some patients treated with infliximab experience a loss of efficacy .
There is a lack of high- quality evidence available on whether adalimumab is an effective treatment for patients who have failed infliximab treatment .
A systematic review was carried out to examine the efficacy and safety of adalimumab for the treatment of CD in patients who have failed infliximab treatment .