Mohan Bala

Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease

BACKGROUND & AIMS The effect of different treatment regimens on antibody responses to infliximab and their clinical significance was examined by using data from ACCENT I. METHODS Patients with Crohns disease (n = 573) received 5 mg/kg infliximab (week 0) and then were randomly assigned to blinded infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo (group I), 5 mg/kg infliximab (group II), or 5 mg/kg infliximab at weeks 2 and 6, followed by 10 mg/kg thereafter (group III). At week 14 or later, patients losing response could cross over to episodic infliximab treatment increased by 5 mg/kg. Samples for antibody determination were collected before the first infusion and at weeks 14, 22, 54, 62, 72, and, if applicable, before and after crossover. RESULTS Through week 72, antibodies to infliximab were detected in 30%, 10%, and 7% of groups I, II, and III, respectively (P < 0.0001). Patients receiving immunomodulators had a lower incidence of antibodies compared with patients receiving infliximab alone (10% and 18%, respectively; P = 0.02). Antibodies were associated with a 12% absolute increase in infusion reactions but no increase in serious infusion reactions or serum sickness-like reactions. In the overall population, similar proportions of antibody-positive and antibody-negative patients achieved clinical response (64% and 62%, respectively; P = NS) or clinical remission (41% and 39%, respectively; P = NS) at week 54. Notably, 86% of patients responded to retreatment, and 63% were in clinical response at week 54; however, fewer antibody-positive group I patients attained clinical remission (31%) compared with those who were antibody negative (37%) or antibody inconclusive (54%) (P = NS). CONCLUSIONS Reduced antibody formation and greater clinical benefit were observed with an induction regimen followed by maintenance treatment compared with a single dose followed by episodic retreatment in Crohns disease patients treated with infliximab.

Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade

Objective: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab. Methods: Patients (n  =  1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (⩽3.3), low (>3.3 to ⩽11), moderate (>11 to ⩽26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score. Results: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy. Conclusion: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.

Annual cost of care for Crohn’s disease: a payor perspective

OBJECTIVE:The aim of this study was to estimate the annual cost of care of patients with Crohns disease according to treatment setting.METHODS:Using a 1994 integrated claims database, patients with a Crohns-related medical claim (ICD-9 code 555) from 10/01/94 to 09/30/95 were included in this analysis. These patients were stratified into three mutually exclusive disease severity groups: group 1, required hospitalization for Crohns; group 2, required chronic glucocorticoid or immunosuppressive drug therapy for >6 months; group 3, all remaining patients. Direct charges (based on reimbursement) and utilization of resources were reported for each group.RESULTS:Six-hundred-seven patients were analyzed: 117(19%) in group 1, 31(5%) in group 2, and 459(76%) in group 3. Average age of all patients was 48 years and 43% of these patients were men. Average annual charges for all patients totaled

Cardiovascular Disease and Risk Factors among Psoriasis Patients in Two US Healthcare Databases, 2001–2002

12,417. Group 1 patients experienced the highest mean charges (

Infliximab improves quality of life in patients with Crohn's disease.

37,135), whereas patients in groups 2 and 3 incurred

The effects of infliximab therapy on health-related quality of life in ulcerative colitis patients

10,033 and

The effects of infliximab maintenance therapy on health-related quality of life

6,277. Approximately 25% of patients accounted for 80% of the total charges.CONCLUSIONS:Crohns disease is associated with high cost. Although a minority of Crohns patients required hospitalization, they tended to have higher utilization and were responsible for a majority of total expenditures. New therapies have the potential to reduce overall cost of care, if they prevent Crohns-related hospitalizations.

Unemployment and disability in patients with moderately to severely active Crohn's disease.

Background: Cardiovascular diseases or risk factors (CVDR) seem to be more common in psoriasis patients than in the general population. Objective: We assessed the relationship of psoriasis with CVDR by analysis of healthcare claims data using a cross-sectional, prevalence-based study design. Patients and Methods: The IMS Health and MarketScan® claims databases were used to identify adults with psoriasis diagnostic codes. Non-psoriasis controls were matched 3:1 based on age, gender, census region and previous medical insurance coverage. Odds ratios evaluated the relative prevalence of CVDR, and Mantel-Haenszel confidence intervals were estimated. Results: CVDR prevalence was generally higher in psoriasis patients than controls in both datasets. Odds ratios for atherosclerosis, congestive heart failure, type 2 diabetes, and peripheral vascular disease were ≧1.20 for psoriasis patients. Elevated disease severity was associated with a higher rate of CVDR, but varied somewhat by dataset and condition. Conclusions: Elevated CVDR rates were found in psoriasis patients compared with controls. This pattern merits further examination.

Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis

ObjectiveThe aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohns disease (CD) inadequately responsive to concomitant therapies. MethodsWe examined responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) from patients enrolled in a previously reported, randomized, placebo-controlled study. Patients with active CD received a single intravenous infusion of either placebo or infliximab 5, 10, or 20 mg/kg. Most patients received stable doses of mesalamine, corticosteroids, azathioprine, or 6-mercaptopurine throughout the study. Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared. ResultsPatients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks (p < 0.001). Infliximab-treated patients also had larger improvements in all IBDQ dimensions: bowel (p = 0.007), social (p = 0.002), emotional (p < 0.001), and systemic (p < 0.001). A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week (p < 0.001), full or a lot of energy (p = 0.019), and no or hardly any difficulty doing leisure or sports activities (p = 0.011), and being extremely or very satisfied with their personal life (p = 0.046). They also significantly differed in responses regarding fatigue, frustration, ability to work, general well-being, depression, anxiety, and anger resulting from bowel problems. ConclusionsThese results indicate that infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and participate in leisure activities, and decreasing feelings of fatigue, depression, and anger.

Infliximab improves health-related quality of life and physical function in patients with psoriatic arthritis

OBJECTIVES:The impact of infliximab induction and maintenance therapy on health-related quality of life (HRQL) was evaluated in patients with ulcerative colitis (UC).METHODS:In two placebo-controlled, double-blind studies (the Active Ulcerative Colitis Trials 1 and 2 [ACT 1 and 2]), 728 patients were randomized to placebo or infliximab 5 mg/kg or 10 mg/kg. Infusions were administered at weeks 0, 2, 6, and every 8 wk thereafter, up to week 22 (ACT 2) or 46 (ACT 1). Changes in Inflammatory Bowel Disease Questionnaire (IBDQ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary (PCS and MCS, respectively) scores were analyzed.RESULTS:Baseline scores for the pooled patient population indicated substantial impairment in HRQL. Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg (40, P < 0.001) and 10-mg/kg (36, P < 0.001) groups compared with the placebo group (28). Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS (6.8 and 5.9, respectively) and MCS (5.9 and 6.4, respectively) compared with placebo (PCS = 3.7, MCS = 3.0, P < 0.01 for all comparisons). Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy (P < 0.001 for all comparisons). Improvement in total IBDQ score correlated significantly (P < 0.001) with improvement in both PCS and MCS scores, and Mayo score.CONCLUSIONS:Infliximab therapy substantially improved HRQL in patients with UC. This benefit was sustained through 1 yr with maintenance infliximab therapy.