Safety Of Infliximab Therapy Research Articles

Efficacy and Safety of Infliximab in HLA-B27-associated Ocular Inflammation Refractory or Intolerant to Conventional Immunomodulatory Therapy.

PurposeTo determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy.MethodsThis was a retrospective observational case series. All cases were uveitic patients with positive HLA-B27, confirmed through HLA testing, resistant or intolerant to conventional immunomodulatory therapy. The primary outcome of the study was to identify the efficacy of infliximab determined by the control of inflammation, duration of remission, and the ability to reduce conventional immunomodulatory therapy. The secondary outcome was an improvement of two or more lines of best-corrected visual acuity (BCVA) on the Snellen visual acuity chart.ResultsTwenty-four patients (38 eyes) were included in the study. All patients were followed for 24 months. Twenty-one (87.5%) patients completed 24 months of follow-up. Sixteen (66.7%) patients had active uveitis at the beginning of therapy. One patient out of these active patients had active inflammation at the end of follow-up period. Thirteen (87.5%) out of sixteen active patients were in steroid-free remission. The mean duration of treatment to induce remission was 16.5 months (range 6–24 months). Corticosteroid was stopped in 19 (90.5%) patients by the end of the study. At the end of the study, in patients who achieved remission, 14 (58.3%) patients were in remission on infliximab therapy and 6 (25%) patients were in remission off infliximab therapy. Of the 38 eyes, 8 (21.05%) showed improvement in BCVA (three eyes had successful cataract extraction with intraocular lens implantation during infliximab therapy with no subsequent inflammation), while 26 eyes (68.4%) had stable BCVA over the 24-month study period. The side effects included allergic reaction, fatigue, cellulitis, headache, restlessness, elevation of liver enzymes, and anemia. Two patients (n = 24, 8.3%) experienced severe adverse effects and the treatment was stopped prematurely in these two patients.ConclusionInfliximab might induce and maintain the steroid-free remission in HLA-B27-associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy.

A 3-year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease.

Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep-TDM) programme for dose adjustment. A 3-year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep-TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD-related surgery and IBD-related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis. In the mep-TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27-0.92; P = .037), IBD-related surgery (HR: 0.14; 95% CI: 0.03-0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17-0.87; P = .022). SIRs were lower in the mep-TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999). This study found that compared to empirical dosing, mep-TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD-related hospitalization and surgery and incidence of SIRs, and increasing long-term durability of treatment effects.

Safety of infliximab in real clinical practice

A wide range of highly effective genetically engineered biological preparations introduced into clinical rheumatology in recent years causes a special interest in their safety.Purpose of the study. Evaluation of the safety of infliximab therapy in patients with rheumatoid arthritis.Materials and methods. The authors' own data, which analyzed the undesirable effects of infliximab in 135 patients with rheumatoid arthritis in actual clinical practice, are presented. A case report of the adverse reaction of combination therapy with leflunomide and infliximab is presented.Results and its discussion. The overall tolerability of infliximab was satisfactory. Adverse events were observed in 28.1 % of cases, including 19.1 % of patients (14.1 %) had serious side effects that required discontinuation of the drug.Findings. In most cases, infliximab is safe for use in actual clinical practice. Patients should be informed about the risks of undesirable effects and the need for a rheumatologist's examination before each infliximab administration before prescribing therapy.

Influence of previous corticosteroid treatment on the efficacy and safety of infliximab therapy in Crohn disease.

To determine the effect of prior corticosteroid treatment on the results of infliximab (IFX) therapy in patients with Crohn disease (CD).Patients with CD treated with at least 3 IFX infusions between March 2009 and April 2017 were divided into steroid group (n = 43) and nonsteroid group (n = 22) and analyzed retrospectively.The cumulative probabilities of clinical remission and response to IFX at weeks 14, 30, 54, and 78 were higher in the steroid group, though this difference was not statistical significant. At the mean interval of 11.7 months following the initiation of IFX treatment, the mucosal healing rate was significantly higher in the steroid group (71.0% vs 22.2%, P < .01). There was no statistical difference in the incidence of adverse reactions between the 2 groups.In CD, patients with prior corticosteroid treatment may increase the response rate to IFX therapy.

INFLIXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE UVEITIS RESISTANT TO CONVENTIONAL IMMUNOMODULATORY THERAPY.

To examine the efficacy and safety of infliximab therapy in the treatment for noninfectious intermediate uveitis resistant to conventional immunomodulatory therapy. Forty-four eyes of 23 patients with resistant noninfectious intermediate uveitis who were treated with infliximab infusions for a minimum period of 3 months were included. Demographic data, clinical data, and fluorescein angiography and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database between August 2005 and February 2014. Clinical response, improvement in ancillary test findings, and major side effects were evaluated. Nineteen patients (82.6%) achieved remission. The mean duration of treatment to induce remission was 3.99 ± 3.06 months (range, 2-14.7). Cystoid macular edema was the only complication observed during the course of the treatment in 1 eye (2.27%). One patient (4.3%) developed major side effects. None of the patients developed central or peripheral demyelinating neuropathies or multiple sclerosis. At 6 months after remission, logarithm of the minimum angle of resolution visual acuity (P = 0.006) and central macular thickness (P = 0.03) showed significant improvement in patients who achieved remission. A significant number of patients achieved remission on infliximab therapy. The incidence of major side effects in our cohort was low.

Induction and maintenance infliximab therapy in children with moderate to severe ulcerative colitis: Retrospective, multicenter study.

Pediatric ulcerative colitis (UC) is a severe disease characterised by the presence of extensive inflammatory lesions in the colon. The administration of intravenous corticosteroids is recommended in patients with acute relapse of the disease, whereas early treatment with cyclosporine, tacrolimus or infliximab is recommended if there is no improvement. The aim of this study was to retrospectively evaluate the efficacy and safety of infliximab therapy in the treatment of moderate-to-severe and severe relapse of pediatric UC. The analysis included 42 children aged 4-18 years (23 girls, 19 boys) treated in 7 pediatric gastroenterology departments in Poland during the past 4 years. The disease duration ranged from 2 to 100 months. The clinical activity of UC ranged from 35 to 85 points according to the PUCAI scale. Twenty-one children were diagnosed with pancolitis, 10 children with extensive UC, and the remaining with the left-sided UC. In the induction therapy infliximab was administered at doses of 5 mg/kg in the 0.2 and 6 weeks, and after the clinical response every 8 weeks to 12 months. Treatment results were assessed in 10 and 54 weeks. After the induction therapy the clinical response was achieved in 14 children (33.33%) and clinical remission in 11 children (26.19%). Two children required surgical treatment, and the remaining 2 suffered from anaphylactic shock. After the maintenance therapy clinical remission was maintained in 12 children (57.14%), whereas 3 children required surgery (colectomy). Infliximab therapy in children with moderate-to-severe UC induces remission and, in some children, proves to be effective in preventing early colectomy.

Evaluation of the infliximab therapy of severe form of pediatric Crohn's disease in Poland: Retrospective, multicenter studies.

Registration of infliximab in Poland has increased chances to induce clinical remission and mucosal healing in the severe form of pediatric Crohn's disease. The aim of this retrospective study was to assess the results and safety of infliximab therapy in the severe form of pediatric Crohn's disease. The study included 153 children with severe form of non-fistulizing Crohn's disease treated with infliximab. The clinical activity of Crohn's disease was assessed according to PCDAI scale, endoscopic scoring was graded according to SES-CD, body mass was measured with body mass index (BMI). Infliximab was administered at the dose 5 mg/kg body mass in the 0.2 and 6th week, and then, after clinical response, every 8 for the period of 12 months. One hundred thirty-six children (88.89%) achieved clinical response after induction therapy and 75.21% of children after the maintenance therapy. 39.68% of children achieved remission as graded with endoscopic scoring SES-CD. There was a statistically significant increase in body weight following the treatment. Side effects such as anaphylaxis, rash, and the activation of EBV infection appeared in 9 children at the time of infliximab injection. In other children the drug was well tolerated. Induction and maintenance therapy with infliximab resulted in clinical remission of Crohn's disease in 75.21% of children, and in the intestinal mucosa healing in 39.68% of children.

Efficacy and Safety of Infliximab Therapy and Predictors of Response in Korean Patients with Crohn's Disease: A Nationwide, Multicenter Study.

PurposeInfliximab is currently used for the treatment of active Crohn's disease (CD). We aimed to assess the efficacy and safety of infliximab therapy and to determine the predictors of response in Korean patients with CD.Materials and MethodsA total of 317 patients who received at least one infliximab infusion for active luminal CD (n=198) and fistulizing CD (n=86) or both (n=33) were reviewed retrospectively in 29 Korean referral centers. Clinical outcomes of induction and maintenance therapy with infliximab, predictors of response, and adverse events were evaluated.ResultsIn patients with luminal CD, the rates of clinical response and remission at week 14 were 89.2% and 60.0%, respectively. Male gender and isolated colonic disease were associated with higher remission rates at week 14. In week-14 responders, the probabilities of sustained response and remission were 96.2% and 93.3% at week 30 and 88.0% and 77.0% at week 54, respectively. In patients with fistulizing CD, clinical response and remission were observed in 85.0% and 56.2% of patients, respectively, at week 14. In week-14 responders, the probabilities of sustained response and remission were 94.0% and 97.1%, respectively, at both week 30 and week 54. Thirty-nine patients (12.3%) experienced adverse events related to infliximab. Serious adverse events developed in 19 (6.0%) patients including seven cases of active pulmonary tuberculosis.ConclusionInfliximab induction and maintenance therapy are effective and well tolerable in Korean patients with luminal and fistulizing CD. However, clinicians must be aware of the risk of rare yet critical adverse events.

Infliximab therapy in pediatric patients 7 years of age and younger.

Infliximab (IFX) is efficacious for induction and maintenance of remission in pediatric patients with moderate-to-severe inflammatory bowel disease (IBD). It has, however, not been studied in patients 7 years old and younger. Our aim was to characterize efficacy and safety of IFX therapy in this cohort. This was a retrospective study of patients with IBD ages 7 years and younger, treated with IFX between 1999 and 2011. Medical records were reviewed for age of diagnosis, disease phenotype, therapy, surgery, IFX infusion dates, dose, and intervals. Outcome measures included physician global assessment, corticosteroid requirement, and adverse events. Thirty-three children (ages 2.4-7 years) were included. Twenty patients had Crohn disease, 4 had ulcerative colitis, and 9 had indeterminate colitis. Maintenance of IFX therapy at 1, 2, and 3 years was 36%, 18%, and 12%, respectively. Patients of age 5 years and younger had the lowest rates of maintenance of therapy at 25% at year 1, and 10% at years 2 and 3 combined. Nine percent of all of the patients demonstrated response measured by the physician global assessment and were steroid free at 1 year. There were 8 infusion reactions. There were no malignancies, serious infections, or deaths. IFX demonstrated a modest response rate and a low steroid-sparing effect in patients with IBD 7 years old and younger. Although this is a limited study, there appears to be a trend for decreased sustained efficacy with IFX in this age group, particularly in children 5 years old and younger, when compared with the previously published literature in older children.

Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO)

Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.

Safety of infliximab therapy in rheumatoid arthritis patients with previous exposure to hepatitis B virus

To evaluate the safety of tumor necrosis factor-α (TNF-α) monoclonal antibody (infliximab) therapy in patients with rheumatoid arthritis (RA) and previous exposure to hepatitis B virus (HBV) who had normal liver function. This is a retrospective study from a 26-week, prospective, multicenter trial in 234 patients with RA who received infusions of infliximab (3mg/kg at week 0, 2, 6, 14 and 22). The medical records of these patients were reviewed, including the information on disease duration, laboratory tests and HBV markers. The data on liver function during the study was analyzed, as well as comparison between patients with previous exposure to HBV and patients without such exposure. Forty-one patients with previous exposure to HBV were HBsAg(-). Forty patients had normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and only one patient with positive anti-HBc showed an elevated ALT level before administration of infliximab, and had a further increase of ALT level at week 14, but decreased thereafter. The average ALT and AST levels rose slightly during the treatment but remained in normal range and the differences were insignificant compared with baseline. There was no statistically significant difference in the incidence of liver function abnormalities during the treatment of infliximab between the patients with previous exposure to HBV and those without such exposure. In patients with RA and previous exposure to HBV but with a negative HBsAg and normal liver function at baseline, liver function abnormalities were not observed during infliximab treatment.

Pre‐existing IgG antibodies cross‐reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease

Infliximab (IFX) is a chimeric murine/human anti-TNF antibody (Ab) used for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Loss of response is common and associated with development of anti-IFX Abs during ongoing therapy. However, human anti-murine immunoglobulin Abs are common and may cross-react with the murine part of IFX. To investigate if Abs binding to IFX's Fab region (IFX-Fab) are present in IBD patients before exposure to IFX, and whether they predict efficacy and safety of IFX therapy. Observational, retrospective cohort study of patients with CD (n=29) and UC (n=22). Pre-treatment levels of IFX-Fab reactive IgG Abs were significantly lower in CD patients in remission after 1year of maintenance IFX (median 91mU/L, n=8) than in the rest of the patients (639mU/L, n=21; P<0.01), and lower than in patients with secondary loss of response in particular (692mU/L, n=7; P<0.01). A cut-off concentration of <439mU IFX-Fab reactive IgG Ab per litre comprised all patients who later obtained long-term sustained remission on IFX (sensitivity 100%, specificity 67%). Similar trends were observed in UC. The pre-treatment levels of IFX-Fab reactive IgG Abs were markedly higher in patients developing infusion reactions to IFX (1037mU/L, n=7) than in the remaining patients (349mU/L, n=44; P=0.036). IFX-Fab reactive IgG antibodies present in serum from IBD patients before infliximab therapy associate with lack of long-term efficacy and safety. Assessments of such antibodies may help clinicians to choose between treatment with infliximab and more humanised agents.

Tu1167 Infliximab Is More Immunogenic and Reaches Lower Trough Levels in Ulcerative Colitis Patients Compared to Crohn's Disease Patients

The aim of this study is to evaluate the clinical and endoscopic efficacy, and safety of infliximab therapy for UC following liver transplantation in patients with PSC. Methods: We evaluated all patients clear diagnosis of UC who underwent Orthotopic Liver Transplantation (OLT) at Ospedali Riuniti of Bergamo between January 2001 and September 2012 and who had received inflixamab therapy for refractory IBD following liver transplantation. Results: Four patients (all men; median age 39 years, range 22 54 years) with UC (3) and pouchitis (1) who underwent OLT were identified. Three patients (75%) experienced sustained improvement of IBD. Mucosal healing was observed in one of three patients (33%). Steroid treatment was interrupted during infiximab therapy in all patients. Adverse events included only one infection: molluscum contagiosum on face of one patient, treated with laser-therapy with resolution of symptoms. No malignancies were observed in all patients following infliximab therapy. No hepatic reject was documented while on infliximab therapy. One patient 25%) presented a recurrence of PSC two years before infliximab therapy (three years after OLT) and he underwent a second OLT after 5 years after the first. Conclusions: Infliximab therapy appears to be effective in patients with refractory ulcerative colitis after liver transplantation. Although no complications of hepatic graft function or reject were observed, additional largest studies are need to evaluate the safety’s profile of biological therapy combined to anti-reject treatment in patients with refractory IBD following liver transplantation.

P348 The efficacy and safety of infliximab therapy in Korean patients with Crohn's diseases: a retrospective, multicenter study

P348 The efficacy and safety of infliximab therapy in Korean patients with Crohn's diseases: a retrospective, multicenter study

Biological therapy of patients with severe psoriasis

Results of the clinical survey of 22 patients suffering from heavy forms of psoriasis have been submitted. The efficiency and safety of infliximab therapy has been evaluated during 48 weeks of patients’ survey.

Importance of trough levels and antibody titers on the efficacy and safety of Infliximab therapy in inflammatory bowel disease

Introduction: Infliximab is effective for the treatment of refractory inflammatory bowel disease (IBD). Nevertheless, up to 40% of patients lose response to infliximab and 10% develops severe side effects or allergic reaction. The aim of this study was to assess the clinical value of measuring infliximab trough levels (TL) and antibodies to infliximab (ATI) concentrations in IBD patients who lost response or developed adverse reaction to infliximab therapy.

Sa1896 The Efficacy and Safety of Infliximab Therapy in Korean Patients With Crohn's Diseases: A Retrospective, Multicenter Study

Sa1896 The Efficacy and Safety of Infliximab Therapy in Korean Patients With Crohn's Diseases: A Retrospective, Multicenter Study

Long-Term Efficacy and Safety of Infliximab in the Treatment of Behçet’s Disease

Purpose: To assess the long-term efficacy and safety of infliximab therapy for the treatment of Behçet’s disease patients with ocular involvement who failed to respond or did not tolerate conventional treatment.Methods: Retrospective study of 12 patients treated with infliximab at a starting dose of 5 mg/kg.Results: Infliximab was infused during a mean of 31.43 months. The mean follow-up period was 35.77 months (range: 6−94). All patients achieved remission, 7 of whom did not need any adjuvant immunosuppressive therapy and 9 of whom were able to discontinue systemic corticosteroids. Visual acuity remained stable or improved in 20/21 eyes. Ten patients did not report any side effect of the medication or those were mild and tolerable. We observed two major adverse events requiring withdrawal of infliximab.Conclusions: Infliximab therapy is an effective biologic agent for the treatment of ocular inflammation in Behçet’s disease unresponsive to the standard immunosuppressive therapy.

Short‐term study of infliximab treatment for Crohn's disease in China

To determine the effectiveness and safety of short-term treatment of infliximab (IFX) in a group of Chinese patients with active Crohn's disease (CD). Patients with established diagnosis of active CD were treated with IFX intravenously with a dose of 5 mg/kg at week 0, 2, 6. Clinical assessments were performed at baseline (week 0) and every week after IFX infusion until 8 weeks after the induction dose. Fourteen patients (nine male, five female) with a mean age of 29.7 years (range from 15 to 65 years) were included in the analysis. The mean subjective scores were decreased from 2.85 ± 0.57 at baseline to 1.3 ± 0.4 at week 14 (P < 0.05). The mean Harvey-Bradshaw index was 7.9 ± 1.5 at baseline and 2.3 ± 1.0 at week 14. The levels of erythrocyte sedimentation rate, serum C-reactive protein, total protein (TP) and albumin (ALB) were significantly improved during the 14-week period. Colonoscopy showed a remarkable improvement. Mild and transient adverse events including skin itching, headache and elevation of serum alanine aminotransferase and aspartate transaminase were each observed in one patient. Severe anemia, leucopenia and thrombocytopenia at week 27 after three infusions of IFX were observed in one patient. Treatment with three infusions of IFX at a dose of 5 mg/kg was effective for induction of remission for active CD patients who failed to respond to conventional therapies. Study of long-term efficacy and safety of IFX therapy is warranted for further investigations.

Efficacy and safety of infliximab therapy in plaque psoriasis patients previously treated with etanercept: Analysis of PSUNRISE

Efficacy and safety of infliximab therapy in plaque psoriasis patients previously treated with etanercept: Analysis of PSUNRISE