Parvez Mulani

Effects of Adalimumab Therapy on Incidence of Hospitalization and Surgery in Crohn's Disease: Results From the CHARM Study

BACKGROUND & AIMS We determined the effects of adalimumab maintenance treatment on the risks of hospitalization and surgery in Crohns disease (CD). METHODS A total of 778 patients with CD were randomized to placebo, adalimumab 40 mg every other week or adalimumab 40 mg weekly, all after an 80-mg/40-mg adalimumab induction regimen. All-cause and CD-related hospitalizations and major CD-related surgeries were compared between the placebo and adalimumab groups (every other week, weekly, and both combined) using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS Both 3- and 12-month hospitalization risks were significantly lower for patients who received adalimumab. Hazard ratios for all-cause hospitalization were 0.45, 0.36, and 0.40 for the adalimumab every other week, weekly, and combined groups, respectively (all P < .01 vs placebo). Hazard ratios for CD-related hospitalization were 0.50, 0.34, and 0.42, respectively (all P < .05). Cox model estimates demonstrated adalimumab every other week and weekly maintenance therapies were associated with 52% and 60% relative reductions in 12-month, all-cause hospitalization risk, and 48% and 64% reductions in 12-month risk of CD-related hospitalization. The combined adalimumab group was associated with 56% reductions in both all-cause and CD-related hospitalization risks. Fewer CD-related surgeries occurred in the adalimumab every other week, weekly, and combined groups compared with placebo (0.4, 0.8, and 0.6 vs 3.8 per 100 patients; all P < .05). CONCLUSIONS Patients with moderate-to-severe CD treated with adalimumab had lower 1-year risks of hospitalization and surgery than placebo patients.

Adalimumab for the Treatment of Moderate to Severe Hidradenitis Suppurativa: A Parallel Randomized Trial

BACKGROUND Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults. OBJECTIVE To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-α antibody, in patients with moderate to severe HS. DESIGN Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255) SETTING 26 academic and private practice medical centers in the United States and Europe. PATIENTS 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics. INTERVENTION Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physicians Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31. MEASUREMENTS The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16. RESULTS At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2. LIMITATIONS Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders. CONCLUSION Adalimumab dosed once per week alleviates moderate to severe HS. PRIMARY FUNDING SOURCE Abbott Laboratories.

The costs of Crohn's disease in the United States and other Western countries: a systematic review

ABSTRACT Objective: To conduct a critical and systematic literature review of the costs of Crohns disease (CD) in Western industrialized countries. Research design and methods: Studies published in English that described the cost of CD in Western industrialized countries were identified using three major databases (Medline, EMBASE, and ISI Web of Science). Studies were reviewed and rated based on their relevance to cost of illness and the reliability of the estimates. All costs were adjusted for inflation to 2006 values. Results: Estimated direct medical costs were

Adalimumab Induces Deep Remission in Patients With Crohn's Disease

18 022–18 932 per patient with CD per year in the United States, and €2898–6960 in other Western countries. Hospitalizations accounted for 53–66% of direct medical costs, with an average cost-per-hospitalization of

Systematic review: the costs of ulcerative colitis in Western countries

37 459 in the United States. Estimated indirect costs accounted for 28% of the total cost in the United States and 64–69% in Europe. Costs differed greatly by disease severity. Costs of patients with severe disease were 3- to 9-fold higher than patients in remission. Direct medical costs in the United States for patients in the top 25% of total costs averaged

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

60 582 per year; costs of patients in the top 2% averaged more than

Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn’s disease

300 000 per year. Combining prevalence rates, the total economic burden of CD was

Comparative Effectiveness Without Head-to-Head Trials: A Method for Matching-Adjusted Indirect Comparisons Applied to Psoriasis Treatment with Adalimumab or Etanercept

10.9–15.5 billion in the United States and €2.1–16.7 billion in Europe. Limitations: This review is limited by the research quality and variations of the individual studies reviewed, and only includes English articles. Conclusions: This updated literature synthesis demonstrated the substantial total cost burden of CD, of which hospitalizations accounted for more than half of direct medical costs.

The effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: A randomized clinical trial

BACKGROUND & AIMS Patients with moderate to severe ileocolonic Crohns disease (CD) who received adalimumab induction and maintenance therapy had greater rates of mucosal healing than patients who received placebo after adalimumab induction therapy in a 52-week trial (EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing). We investigated whether this treatment also induced deep remission-a composite clinical and endoscopic end point. METHODS Rates of deep remission, defined as the absence of mucosal ulceration and CD Activity Index scores less than 150, were compared between patients given continuous adalimumab and those given only induction therapy followed by placebo. We assessed the relationships between deep remission and other outcomes among patients who received adalimumab. The outcomes of patients with deep remission were compared with those of patients with only the absence of mucosal ulceration or only clinical remission. RESULTS Rates of deep remission were 16% in patients given adalimumab vs 10% in those given placebo (P = .34) at week 12, and 19% vs 0% (P < .001) at week 52. Rates of deep remission were greatest among patients who received adalimumab and had CD for 2 years or less (33% at weeks 12 and 52). At week 52, patients who achieved deep remission at week 12 required significantly fewer adalimumab treatment adjustments, hospitalizations, and CD-related surgeries; had significantly less activity impairment; and had better quality of life and physical function compared with patients not achieving deep remission. Deep remission generally was associated with better outcomes than only an absence of mucosal ulceration; outcomes of patients with deep remission vs only clinical remission were similar. Deep remission was associated with estimated total cost savings of

Risks of developing psychiatric disorders in pediatric patients with psoriasis

10,360 (from weeks 12 through 52) compared with lack of deep remission. CONCLUSIONS In an exploratory study of patients with moderate to severe ileocolonic CD who received adalimumab induction and maintenance therapy, patients achieving deep remission appeared to have better 1-year outcomes than those not achieving deep remission. These findings should be validated in large, prospective trials. ClinicalTrials.gov number: NCT00348283.