Starting Infliximab Therapy Research Articles

Confocal endomicroscopic evaluation of colorectal squamous metaplasia and dysplasia in ulcerative colitis

A 52-year-old woman with a 20-year history of ulcerative colitis (UC) underwent surveillance colonoscopy. She had received prednisone and then started infliximab therapy 4 months before colonoscopy for diarrhea and rectal bleeding, which resolved, but arthralgias and paresthesias led to infliximab discontinuation after the third induction dose. At the time of colonoscopy, the patient was asymptomatic on mesalamine monotherapy. Colonoscopy revealed only left-sided colitis and pseudopolyps abutting the anal verge. Random biopsies revealed moderate active colitis consistent with UC in the distal 40 cm of the colon. Rectal biopsy specimens 10 cm from the anus incidentally also contained areas of squamous epithelium with at least intermediate-grade squamous intraepithelial neoplasia. Biopsies of the distal rectum revealed inflammatory pseudopolyps as well as squamous epithelium with high-grade squamous intraepithelial neoplasia.

Infliximab may be effective in the treatment of steroid-resistant eosinophilic fasciitis: report of three cases

EF is a rare fibrosing disorder that may involve skin and internal organs. Current therapies include moderate- to high-dose glucocorticoids with or without use of immunosuppressives. We report three cases of steroid-resistant EF in clinical practice who were treated with 3 mg/kg every 8 weeks infliximab therapy. All patients noticed an improvement in their symptoms, joint contractures and skin thickening within 8 weeks of starting infliximab therapy, ultimately leading to a drug-free remission (range 1-3 years). Based on this and other reported cases, infliximab may be beneficial in patients with steroid-resistant EF.

An Eight-Gene Blood Expression Profile Predicts the Response to Infliximab in Rheumatoid Arthritis

BackgroundTNF alpha blockade agents like infliximab are actually the treatment of choice for those rheumatoid arthritis (RA) patients who fail standard therapy. However, a considerable percentage of anti-TNF alpha treated patients do not show a significant clinical response. Given that new therapies for treatment of RA have been recently approved, there is a pressing need to find a system that reliably predicts treatment response. We hypothesized that the analysis of whole blood gene expression profiles of RA patients could be used to build a robust predictor to infliximab therapy.Methods and FindingsWe performed microarray gene expression analysis on whole blood RNA samples from RA patients starting infliximab therapy (n = 44). The clinical response to infliximab was determined at week 14 using the EULAR criteria. Blood cell populations were determined using flow cytometry at baseline, week 2 and week 14 of treatment. Using complete cross-validation and repeated random sampling we identified a robust 8-gene predictor model (96.6% Leave One Out prediction accuracy, P = 0.0001). Applying this model to an independent validation set of RA patients, we estimated an 85.7% prediction accuracy (75–100%, 95% CI). In parallel, we also observed a significantly higher number of CD4+CD25+ cells (i.e. regulatory T cells) in the responder group compared to the non responder group at baseline (P = 0.0009).ConclusionsThe present 8-gene model obtained from whole blood expression efficiently predicts response to infliximab in RA patients. The application of the present system in the clinical setting could assist the clinician in the selection of the optimal treatment strategy in RA.

Adalimumab therapy of psoriasis and psoriatic arthritis in a patient with cirrhosis of the liver

To the Editor: We report a 57-year-old male patient with psoriasis and psoriatic arthritis (PA), diabetes, and hereditary α-1-antitrypsin deficiency, resulting in histologically confirmed micronodular cirrhosis of the liver. Mutilating PA was diagnosed 11 years earlier, and a systemic treatment with methotrexate (MTX) was initiated. Because of a considerable elevation of liver enzyme levels, MTX had to be interrupted. A few years later, the patient started infliximab therapy. Although the skin and the PA showed a dramatic improvement, infliximab had to be discontinued because of severe thrombocytopenia.

Tuberculous Colitis in a Patient with Crohnʼs Disease after Treatment with Infliximab

Purpose: Tuberculous Colitis is a rare manifestation of abdominal tuberculosis (TB). It is located in the ileocecal area in 90% of cases. Since 10/01 a boxed warning is added to infliximab package insert advising physicians to screen for TB before treatment. We report a case of TB colitis in a patient with negative PPD & Crohn's disease after starting infliximab. Methods: Our patient is a 23 year old Peruvian female who presented with abdominal pain, weight loss, diarrhea & hematochezia. Colonoscopy in 3/07 revealed edematous, friable and inflammed rectosigmoid. Biopsies and Prometheus-7 panel were consistent with Crohn's disease. Biopsy specimens were negative for AFB. She denied any h/o TB or HIV. She was started on Mesalamine with no relief & subsequently started on azathioprine. Colonoscopy in 7/07 showed severe Crohn's colitis in left colon. Infliximab was considered & patient had a PPD test which was negative with completely normal CXR. First dose of infliximab was given in 8/07 & second dose 2 weeks later. 4 weeks after starting infliximab she was hospitalised with high grade fever, diarrhea & abdominal pain. CT scan was negative for retroperitoneal adenopathy or abscesses & showed diffuse colonic thickening. Colonoscopy showed severely worsened pancolitis with biopsies from entire colon positive for AFB. Repeat PPD & CXR remained negative. She denied recent travel, ill contact or cough. She was started on quadruple therapy for possible TB & biopsy PCR confirmed the diagnosis of TB colitis. The patient improved dramatically on TB medications & has gained 20 lbs. Conclusion: Infliximab is a chimeric monoclonal antibody to TNF-α. One of its FDA approvals is for treatment of Crohn's disease. From 1998–2001, out of 147,000 patients who received infliximab for RA or Crohn's disease, 70 cases of TB associated with infliximab were reported. The median time to onset from starting infliximab therapy to TB diagnosis is 10 months (1–72 months). TB Colitis can present as ulcerations, stenosis & shortening. It can mimic Crohn's disease making diagnosis difficult. CXR is often normal & 15–20% patients with abdominal TB present with active pulmonary TB. Retracted cecum & asymmetric wall thickening have been reported to be suggestive of TB. Clinicians should be vigilant for TB in patients on infliximab even if pretreatment PPD is negative, especially if risk factors for TB are present. Patients with demographic risk factors, h/o BCG, exposure to TB, GI resection & occupational exposure are at high risk for TB. Currently recommended screening such as risk assessment, tuberculin skin testing and CXR prior to anti-TNF-α treatment can reduce TB rates by up to 90% but newer screening interferon gamma assays may enhance screening efficacy.

Non therapeutic 6-thioguanine (6TG) levels in IBD patients prior to starting Infliximab therapy

Non therapeutic 6-thioguanine (6TG) levels in IBD patients prior to starting Infliximab therapy

Non therapeutic 6-thioguanine (6TG) levels in IBD patients prior to starting Infliximab therapy

Non therapeutic 6-thioguanine (6TG) levels in IBD patients prior to starting Infliximab therapy

The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study

To investigate the influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in rheumatoid arthritis (RA) and to compare it to infliximab in combination with other disease-modifying anti-rheumatic drugs. RA patients starting infliximab therapy were prospectively followed from January 2000. Every 3 months data were collected regarding disease activity (DAS28), adverse events and treatment changes. In the primary analyses all patients were classified into a leflunomide group (LEF group) if they had used leflunomide during infliximab therapy or within 6 months prior to starting infliximab therapy, the latter because of the long half-life of leflunomide. All other patients were considered as controls (non-LEF group). Secondary drug survival analyses were performed with the LEF group consisting only of patients on active leflunomide at the start of infliximab (active LEF group). A total of 162 RA patients started infliximab therapy (57 in the LEF group, 105 in the non-LEF group). No statistically significant differences in baseline characteristics were observed between the groups. Maximum follow-up time was 46 months for both groups. No differences in drug survival, disease activity or adverse events were observed between the groups. In both groups an increase in patients positive for antinuclear antibodies (ANA) was seen. ANA positivity at start did not predict DAS28 or the occurrence of adverse events. Secondary drug survival analyses showed no differences between the active LEF group and the non-LEF group. The results indicate that the administration of infliximab after or simultaneously with leflunomide is safe and efficacious in RA patients.

Managing immunogenic responses to infliximab: treatment implications for patients with Crohn's disease.

Infliximab is a tumour necrosis factor (TNF)-alpha antagonist that has revolutionised the treatment of Crohn's disease and rheumatoid arthritis. However, infliximab therapy can be complicated by a variety of adverse reactions. Acute infusion reactions occur during or shortly after infusion and typically consist of fever, chills, nausea, dyspnoea and headaches. Delayed reactions, characterised by myalgias, arthralgias, fever, rash, pruritus, facial, hand or lip oedema, dysphagia, urticaria, sore throat and headache may occur 3-12 days after infusion. Although the mechanisms of these reactions are not yet clearly defined, emerging evidence indicates that these reactions may be associated with the immune response against infliximab and the development of antibodies to infliximab.A number of studies have identified protective factors that may minimise adverse reactions, presumably related to the immune response against infliximab. Factors that may be protective by helping to establish immune tolerance for the foreign infliximab protein include concomitant administration of immunomodulators or corticosteroids, starting infliximab therapy with a 0, 2, 6-week induction regimen, maintenance dose administration with infusions every 8 weeks or less, and avoiding long periods between infusions. Infliximab therapy also may have other immunological consequences. There is evidence that infliximab may impede the appropriate immune response to a number of pathogens, prohibiting its use in patients with active infections. In addition, patients should be screened and appropriately treated for tuberculosis before initiating infliximab therapy. The development of autoantibodies, such as antinuclear antibody or anti-ds-DNA, has also been described with infliximab therapy, although the development of clinical lupus-like syndrome is rare. While there is a theoretical risk of increased rate of malignancies due to antagonism of TNFalpha, to date there is no clear evidence of such an effect. In addition, cardiac and neurological adverse events associated with infliximab therapy have been described. The mechanism for these adverse events is unclear. In summary, infliximab therapy can be an effective treatment for Crohn's disease; however, a number of immunological consequences and adverse events may complicate the infusion of this agent. Appropriate prophylaxis and therapy of these adverse reactions will allow infliximab to be used safely in the vast majority of patients.