Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate.

BACKGROUND: Psoriasis is associated with increased risk for cardiovascular disease. OBJECTIVE: To compare major cardiovascular event risk in psoriasis patients receiving methotrexate or tumor necrosis factor-α inhibitor (TNFi) and to assess TNFi treatment duration impact on major cardiovascular event risk. METHODS: Adult psoriasis patients with ≥2 TNFi or methotrexate prescriptions in the Truven MarketScan Databases (Q1 2000-Q3 2011) were classified as TNFi or methotrexate users. The index date for each of these drugs was the TNFi initiation date or a randomly selected methotrexate dispensing date, respectively. Cardiovascular event risks and cumulative TNFi effect were analyzed by using multivariate Cox proportional-hazards models. RESULTS: By 12 months, TNFi users (N = 9148) had fewer cardiovascular events than methotrexate users (N = 8581) (Kaplan-Meier rates: 1.45% vs 4.09%: P < .01). TNFi users had overall lower cardiovascular event hazards than methotrexate users (hazard ratio = 0.55; P < .01). Over 24 months' median follow-up, every 6 months of cumulative exposure to TNFis were associated with an 11% cardiovascular event risk reduction (P = .02). LIMITATIONS: Lack of clinical assessment measures. CONCLUSIONS: Psoriasis patients receiving TNFis had a lower major cardiovascular event risk compared to those receiving methotrexate. Cumulative exposure to TNFis was associated with a reduced risk for major cardiovascular events.

Increased risk of venous thromboembolic events with corticosteroid vs biologic therapy for inflammatory bowel disease.

BACKGROUND & AIMS: We investigated whether treatment of active inflammatory bowel disease with biologic agents is associated with a reduced risk of venous thromboembolic events (VTEs) compared with corticosteroid therapy. METHODS: We performed a retrospective analysis of 15,100 adults with inflammatory bowel disease who were identified from the Truven Health MarketScan databases. We analyzed data from patients who received 6 months of continuous medical and prescription coverage before and 12 months after their first diagnosis and had no VTE during the 6 months before they first received biologic or corticosteroid therapy. The outcome assessed was any VTE that occurred during the 12-month follow-up period. A multivariate logistic regression model was used to evaluate the effects of biologic, corticosteroid, and combination therapies (biologics and corticosteroids) on VTE risk. RESULTS: Three hundred twenty-five VTEs occurred during the study period (in 2.25% of patients receiving only corticosteroids, in 0.44% of patients receiving biologics, and in 2.49% of patients receiving combination therapy). Compared with patients receiving only corticosteroids, the odds ratio for VTE in patients receiving only biologics was 0.21 (95% confidence interval, 0.05-0.87) in the multivariate model, and the odds ratio for VTE in patients on combination therapy was 1.01. CONCLUSIONS: Compared with treatment with only a biologic agent, corticosteroid therapy is associated with a nearly 5-fold increase in risk for VTE. Combination therapy with corticosteroids and biologic agents was associated with the same risk for VTE as that of corticosteroids alone. Corticosteroids therefore appear to increase risk for VTE.

Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis.

BACKGROUND & AIMS: Adalimumab is effective for induction and maintenance of remission in patients with moderate to severe ulcerative colitis (UC). We assessed whether adalimumab, in addition to standard UC therapy, reduced the risk for hospitalization (from all causes, from complications of UC, or from complications of UC or the drugs used to treat it) and colectomy in patients with moderate to severe UC compared with placebo. METHODS: Data were combined from patients that received induction therapy (a 160-mg dose followed by an 80-mg dose of adalimumab) or placebo in 2 trials (ULTRA 1 and ULTRA 2; n = 963). The risks of hospitalization and colectomy were compared between groups using unadjusted rates during the 8-week induction period, and patient-year-adjusted rates during 52 weeks. Statistical differences between groups were determined using the χ(2) method and Z score normal approximations. Numbers of hospitalizations were compared using Poisson regression with time offset. RESULTS: Significant reductions in risk of all-cause, UC-related, and UC- or drug-related hospitalizations (by 40%, 50%, and 47%, respectively; P < .05 for all comparisons) were observed within the first 8 weeks of adalimumab therapy compared with placebo. Significantly lower incidence rates for all-cause (0.18 vs 0.26; P = .03), UC-related (0.12 vs 0.22; P = .002), and UC- or drug-related (0.14 vs 0.24; P = .005) hospitalizations were observed during 52 weeks of adalimumab therapy compared with placebo. Rates of colectomy did not differ significantly between patients given adalimumab vs placebo. CONCLUSIONS: In patients with moderate to severe UC, the addition of adalimumab to standard of care treatment reduced the number of hospitalizations for any cause, as well as for UC-related and UC- or drug-related complications, compared with placebo. ClinicalTrials.gov numbers, NCT00385736 and NCT00408629.

Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis?

BACKGROUND: This study assessed the impact of simultaneous achievement of clinical, functional and structural efficacy, herein referred to as comprehensive disease control (CDC), on short-term and long-term work-related outcomes, health-related quality of life (HRQoL), pain and fatigue. METHODS: Data were pooled from three randomised trials of adalimumab plus methotrexate for treatment of early-stage or late-stage rheumatoid arthritis (RA). CDC was defined as 28-joint Disease Activity Score using C reactive protein <2.6, Health Assessment Questionnaire <0.5 and change from baseline in modified Total Sharp Score ≤0.5. Changes in scores at weeks 26 and 52 for work-related outcomes, Short Form 36 (SF-36) physical (PCS) and mental component scores (MCS), a Visual Analogue Scale measuring pain (VAS-Pain) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were compared between patient groups defined by achievement of CDC at week 26 using linear regression with adjustment for baseline scores. RESULTS: Patients with RA who achieved CDC at week 26 (n=200) had significantly greater improvements in VAS-Pain (46.9 vs 26.9; p<0.0001), FACIT-F (13.3 vs 7.5; p<0.0001), SF-36 PCS (19.7 vs 8.9; p<0.0001) and SF-36 MCS (8.1 vs 5.0; p=0.0004) than those who did not (n=1267). Results were consistent at week 52 and among methotrexate-naive patients with early RA, methotrexate-experienced patients with late-stage RA and patients with inadequate response to methotrexate. CONCLUSIONS: Patients with RA who achieved CDC at week 26 had improved short-term and long-term HRQoL, pain, fatigue and work-related outcomes compared with patients who do not. These results demonstrate that the joint achievement of all CDC components provides meaningful benefits to patients. TRIAL REGISTRATION NUMBERS: DE019: NCT00195702, PREMIER: NCT00195702, OPTIMA: NCT00195702.

Psoriasis and risk of diabetes-associated microvascular and macrovascular complications.

BACKGROUND: Psoriasis's effect on diabetes onset is well documented, but its effect on course of diabetes is poorly understood. OBJECTIVE: We sought to compare risks of developing microvascular and macrovascular complications between diabetic patients with and without psoriasis. METHODS: Adults with 2 or more diabetes diagnoses selected from MarketScan databases (Truven Health Analytics Inc, Ann Arbor, MI) (2000-2006) were classified into 2 cohorts: 2 or more psoriasis diagnoses and without psoriasis diagnosis. Patients with psoriasis were matched using propensity score, and exactly matched using age, sex, and diabetes characteristics with patients without psoriasis. Outcomes were compared between cohorts using Cox regression models. RESULTS: In all, 6164 diabetic patients with psoriasis (27% moderate to severe) were matched to 6164 diabetic patients without psoriasis. Patients with psoriasis were significantly more likely to develop microvascular events than patients without psoriasis overall (hazard ratio [HR] 1.14, P < .001) and by psoriasis severity (mild: HR 1.13, P = .004; moderate to severe: HR 1.16, P = .038). Risk of macrovascular events was higher for patients without psoriasis overall (HR 1.13, P = .001) and those with mild psoriasis (HR 1.15, P = .003), but not for moderate to severe cases (HR 1.10, P = .210). LIMITATIONS: Psoriasis to diabetes association may be underestimated. CONCLUSION: Among diabetic patients, psoriasis is generally associated with higher rates of microvascular and macrovascular complications. Greater psoriasis severity did not increase risk of diabetic complications.

Adalimumab induces deep remission in patients with Crohn's disease.

BACKGROUND & AIMS: Patients with moderate to severe ileocolonic Crohn's 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 $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.

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 Physician's 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 effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis.

BACKGROUND: Psoriasis significantly impairs work productivity and daily activities. OBJECTIVES: We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis. METHODS: Data were from the first 16 weeks of the Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL (REVEAL). Outcomes as measured by the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-Psoriasis) included employment status, total work productivity impairment, and total activity impairment. Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response (≥ 75% improvement in Psoriasis Area and Severity Index responders) on WPAI-Psoriasis outcomes. Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity. RESULTS: Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo (15.5 and 11.1 percentage points, respectively; P < .001). Unemployment rate, total work productivity impairment, and total activity impairment were significantly associated with greater baseline psoriasis severity. Changes in WPAI outcomes were significantly correlated with greater psoriasis severity. The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures (Psoriasis Area and Severity Index and Physician Global Assessment). LIMITATIONS: REVEAL only included WPAI data for 16 weeks. Therefore, long-term impact of adalimumab treatment on productivity outcomes could not be assessed. In addition, information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis. CONCLUSIONS: Adalimumab reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis.

Risks of developing psychiatric disorders in pediatric patients with psoriasis.

BACKGROUND: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. OBJECTIVE: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. METHODS: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. RESULTS: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045). LIMITATIONS: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. CONCLUSIONS: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

Increased risks of developing anxiety and depression in young patients with Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is associated with substantial psychosocial burden and increased risks for mental health disorders. This retrospective cohort study compared the risks of developing anxiety disorders and depression and incidences of psychotropic medication use between young CD patients and matched CD-free controls. METHODS: Medical claims, prescription drug claims, enrollment, and demographic data for patients <18 years diagnosed with CD were obtained from the MarketScan database (1 January 2000-30 June 2006). Each CD patient was matched with five CD-free controls based on exact age, sex, and months of health plan enrollment. Incidence rates and risks of developing anxiety disorders and depression and psychotropic medication use in the 6 months after the index date were compared, as were risks of developing persistent anxiety or depression (receiving medical services related to a diagnosis of anxiety or depression or psychotropic therapy for >1 year). RESULTS: After adjustment for patient characteristics, the risks of developing anxiety disorders (hazard ratio (HR) [95% confidence interval (CI);[equals;2.28 [1.65-3.17]) and depression (HR [95% CI;[equals;1.74 [1.35-2.25]) after CD diagnosis were significantly greater for the CD cohort (N=2,144) than for CD-free controls (N=10,720). Patients with CD also had greater risks of developing persistent anxiety and persistent depression (HR [95% CI;[equals;4.35 [2.22-8.50] and 2.75 [1.73-4.38], respectively). CONCLUSIONS: Compared with matched CD-free controls, young patients with CD had significantly greater risks of developing anxiety disorders and depression, were more likely to receive psychotropic treatments, and had significantly greater risks of developing persistent anxiety and depression.

Effect of adalimumab on work productivity and indirect costs in moderate to severe Crohn's disease: a meta-analysis.

OBJECTIVE: To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn's disease (CD) using a meta-analysis of clinical trials. METHODS: Study-level results were pooled from all clinical trials of adalimumab for moderate to severe CD in which work productivity outcomes were evaluated. Work Productivity and Activity Impairment Questionnaire outcomes (absenteeism, presenteeism and total work productivity impairment [TWPI]) were extracted from adalimumab trials. Meta-analyses were used to estimate pooled averages and 95% CIs of one-year accumulated reductions in work productivity impairment with adalimumab. Pooled averages were multiplied by the 2008 United States national average annual salary ($44,101) to estimate per-patient indirect cost savings during the year following adalimumab initiation. RESULTS: The four included trials (ACCESS, CARE, CHOICE and EXTEND) represented a total of 1202 employed adalimumab-treated patients at baseline. Each study followed patients for a minimum of 20 weeks. Pooled estimates (95% CIs) of one-year accumulated work productivity improvements were as follows: -9% (-10% to -7%) for absenteeism; -22% (-26% to -18%) for presenteeism; and -25% (-30% to -20%) for TWPI. Reductions in absenteeism and TWPI translated into per-patient indirect cost savings (95% CI) of $3,856 ($3,183 to $4,529) and $10,964 ($8,833 to $13,096), respectively. CONCLUSION: Adalimumab provided clinically meaningful improvements in work productivity among patients with moderate to severe CD, which may translate into substantial indirect cost savings from an employer's perspective.

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.

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. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.

Effects of adalimumab versus placebo on risk of symptom worsening in psoriasis and subsequent impacts on health-related quality-of-life: analysis of pooled data from two randomized, double-blind, placebo-controlled, multicentre clinical trials.

BACKGROUND: Rates and impacts of worsening symptoms in patients with psoriasis have not been well characterized. OBJECTIVES: To assess the risk of clinically relevant worsening of psoriasis symptoms in patients treated with adalimumab versus placebo and to determine the health-related quality-of-life (HRQOL) impacts of such worsening. METHODS: The cumulative incidence of worsening was compared for adalimumab (40 mg every other week following an 80 mg induction dose) versus placebo using data from two phase III randomized, placebo-controlled trials (CHAMPION and REVEAL). Clinically relevant worsening of psoriasis was defined as a follow-up visit with a ≥25% increase in the Psoriasis Area and Severity Index (PASI) from baseline or a ≥5-unit increase in the Dermatology Life Quality Index from baseline during the initial 16-week double-blind treatment periods. Patients with versus without worsening were compared in terms of pain, work productivity and activity impairment (WPAI) and the mental and physical component summary (MCS and PCS) scores of the Short-Form 36 Health Survey. A subgroup analysis was performed for patients with PASI 10-20 at baseline. RESULTS: The 17-week risk of clinically relevant worsening was 37.0% (95% CI 26.1, 46.3) for placebo (n = 445) and 4.2% (95% CI 2.0, 6.3) for adalimumab-treated patients (n = 914) [p < 0.0001]. Patients with versus without worsening experienced substantially increased pain, increased WPAI and greater impairment in MCS and PCS. Results were similar for patients with PASI 10-20 at baseline. LIMITATIONS: The short study duration may not reflect long-term outcomes. CONCLUSION: Clinically relevant worsening of psoriasis symptoms was associated with substantial worsening of HRQOL. Adalimumab treatment was associated with a substantially reduced risk of clinically relevant worsening.

Benefit-risk analysis of adalimumab versus methotrexate and placebo in the treatment of moderate to severe psoriasis: comparison of adverse event-free response days in the CHAMPION trial.

BACKGROUND: The Comparative Study of Humira versus Methotrexate (MTX) versus Placebo in Psoriasis Patients (CHAMPION) demonstrated superior efficacy of biologic over conventional systemic immunosuppressant therapy in psoriasis. OBJECTIVE: We sought to compare the risk-benefit profile of adalimumab (ADA), MTX, and placebo using data from CHAMPION. METHODS: Patients randomized to ADA (n = 107), MTX (n = 110), or placebo (n = 53) were followed up for 16 weeks. Response (≥75% improvement in Psoriasis Area and Severity Index), days free of adverse events (AEs), moderate to severe AEs, infection-related AEs, and study drug-related AEs were analyzed. RESULTS: ADA treatment was associated with substantially more days (SD) of AE-free response compared with MTX or placebo treatment, respectively: 36.9 (31.1) versus 8.3 (15.9) or 6.7 (18.1) days of response free of any AEs, 43.8 (31.9) versus 11.1 (19.9) or 7.9 (19.9) days of response free of moderate to severe AEs, 48.5 (29.2) versus 12.4 (21.7) or 9.2 (21.8) days of response free of infection-related AEs, and 44.6 (31.4) versus 11.8 (21.1) or 10.0 (24.0) days free of study drug-related AEs (all P < .0001 for ADA vs MTX or placebo). LIMITATIONS: This clinical trial-based analysis may not have captured the full spectrum of AEs in the actual clinical setting. The short (16-week) duration of the trial limited the ability to capture some important but uncommon AEs associated with long-term ADA or MTX use. CONCLUSION: With 4 times as many AE-free response days, ADA demonstrated a superior benefit-risk profile.

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

BACKGROUND: Psoriasis is associated with health-related quality-of-life impairment and depression. OBJECTIVE: We sought to determine the effect of adalimumab on depression symptoms in patients with psoriasis. METHODS: Patients with moderate to severe psoriasis in a randomized, placebo-controlled, double-blind clinical trial were assessed for depression symptoms at baseline and week 12 or early termination (ET) using the Zung Self-rating Depression Scale (ZDS). The effects of adalimumab (40 mg every other week) versus placebo on ZDS score at week 12/ET were assessed using analysis of covariance. Relationships between ZDS and the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index, and the Short Form 36 Health Survey were assessed using Pearson correlations. Changes in ZDS score were compared for patients with and without a 75% or greater reduction in baseline PASI score. RESULTS: Compared with the placebo group (n = 52), the adalimumab group (n = 44) experienced an additional 6-point reduction in ZDS score (95% confidence interval: 2.5-9.5; P < .001) by week 12/ET. Depression improvement was correlated with improvement in PASI (r = 0.5; P < .0001) and Dermatology Life Quality Index (r = 0.5; P < .0001). Greater ZDS score improvement was observed at week 12/ET in responders with a 75% or greater reduction in baseline PASI score than in nonresponders (10.6 [SD = 9.4] vs 1.4 [SD = 9.6]; P < .001). LIMITATIONS: This analysis cannot distinguish whether adalimumab has a direct or indirect effect on depression. CONCLUSIONS: Adalimumab treatment reduced psoriasis symptoms, reduced depression symptoms, and improved health-related quality of life in patients with moderate to severe psoriasis.

Impact of adalimumab on symptoms of psoriatic arthritis in patients with moderate to severe psoriasis: a pooled analysis of randomized clinical trials.

BACKGROUND: Psoriatic arthritis often affects patients with psoriasis. OBJECTIVE: To examine the effect of adalimumab on psoriatic arthritis in patients with moderate to severe psoriasis. METHODS: Data from patients with psoriasis and a reported history of comorbid psoriatic arthritis in 3 randomized, placebo-controlled psoriasis trials of adalimumab were analyzed. RESULTS: Adalimumab (n = 274) reduced the risk of psoriatic arthropathy adverse events by 75% versus placebo (1.1 vs. 4.8%; p = 0.025). Psoriasis/psoriatic arthritis-related pain was significantly reduced (-31.3 vs. -5.6 visual analog scale units; p < 0.0001). At week 16, adalimumab-treated patients were more likely to respond (56.9 vs. 4.5%; p < 0.001) and responded for a greater percentage of follow-up time (39.3 vs. 2.9%; p< 0.0001) than placebo-treated patients (regression model for PASI 75 and ACR 20 responses). CONCLUSION: Adalimumab treatment of moderate to severe psoriasis reduced symptoms of comorbid psoriatic arthritis.

High prevalence of potential drug-drug interactions for psoriasis patients prescribed methotrexate or cyclosporine for psoriasis: associated clinical and economic outcomes in real-world practice.

BACKGROUND: Methotrexate (MTX) and cyclosporine (CYC) may adversely interact with common medications in patients with psoriasis. OBJECTIVE: Our purpose was to investigate the prevalence and outcomes of MTX/CYC polypharmacy. METHODS: We evaluated rates of events that may be associated with drug-related toxicity, health care resource utilization and costs for patients with psoriasis in the Ingenix(R) Impact National Managed Care Database (1999-2007) who were exposed or not exposed to potential drug-drug interactions. RESULTS: Among 4,583 (57.6%) exposed and 3,372 (42.4%) nonexposed patients, nonsteroidal anti-inflammatory drugs and antibiotics were the most common drugs with potential interactions. The exposed patients had significantly greater risks of developing renal [adjusted odds ratio (OR): 2.58; p = 0.0145], gastrointestinal (OR: 1.36; p = 0.0197) and pulmonary events (OR: 1.20; p = 0.0470), and significantly greater health care resource utilization (e.g. OR for inpatient and emergency department visits: 1.47; p < 0.0001) and costs (adjusted incremental cost: USD 1,722; p < 0.0001). CONCLUSIONS: MTX/CYC polypharmacy is prevalent in patients with psoriasis and associated with significant risks.

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 Crohn's 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.

Comparison of two adalimumab treatment schedule strategies for moderate-to-severe Crohn's disease: results from the CHARM trial.

OBJECTIVES: To compare outcomes of induction dosing followed by continuous adalimumab treatment with those of induction dosing with reinitiation of adalimumab (in the event of clinical deterioration) for patients with moderate-to-severe Crohn's disease (CD) who participated in the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM). METHODS: In the CHARM trial, all patients received open-label induction therapy with adalimumab 80 mg and 40 mg at weeks 0 and 2, respectively. In total, 778 patients were randomized at week 4 to one of three groups: (1) placebo after initial induction doses (followed by reinitiation of adalimumab therapy); (2) continuous maintenance treatment with adalimumab 40 mg every other week (e.o.w.); and (3) continuous maintenance treatment with adalimumab 40 mg every week. At/after week 12, patients receiving placebo with flare or non-response could reinitiate open-label adalimumab 40 mg e.o.w., and patients receiving continuous blinded adalimumab therapy could switch to open-label 40 mg e.o.w. Patients in all groups could switch to weekly therapy with continued flare/non-response. In the previously published primary analysis, results for only those patients who had responded at week 4 (decrease in Crohn's Disease Activity Index (CDAI) of > or = 70 points, referred to as "randomized responders") and remained on blinded therapy were analyzed. In this analysis, data from all randomized patients were analyzed based on original randomized treatment using an intention-to-treat analysis, regardless of whether they subsequently switched to open-label therapy. Disease activity, clinical remission, number of flares, Inflammatory Bowel Disease Questionnaire (IBDQ) score, number of CD-related surgeries, and hospitalization incidence were compared between the continuous and induction only/reinitiation adalimumab groups. RESULTS: Results for all outcome measures were superior for both continuous groups compared with the induction only/reinitiation group. On the basis of median CDAI and IBDQ results, patients in both continuous treatment groups achieved statistically significantly greater improvements vs. the induction only/reinitiation group (P < 0.05). At week 56, a significantly greater percentage of patients who had received continuous adalimumab (51% for e.o.w. and 49% for weekly) were in clinical remission vs. the induction only/reinitiation group (38%, P < 0.05). Continuous adalimumab therapy was also associated with fewer flares and fewer CD-related surgeries (P < 0.05). Patients in both continuous adalimumab groups had significantly lower risks of CD-related and all-cause hospitalizations than did patients in the induction only/reinitiation group (P < 0.05). CONCLUSIONS: For patients with active CD, continuous treatment with adalimumab was more effective than a strategy of induction dosing followed by reinitiation of adalimumab with clinical deterioration for maintenance of clinical remission, improved quality-of life outcomes, reduced flares, and a decrease in number of surgeries and risk of hospitalization.

Estimating clinically meaningful changes for the Functional Assessment of Cancer Therapy--Prostate: results from a clinical trial of patients with metastatic hormone-refractory prostate cancer.

OBJECTIVE: To determine clinically meaningful changes (CMCs) for the Functional Assessment of Cancer Therapy-Prostate (FACT-P). METHODS: We obtained data from a Phase III trial of atrasentan in metastatic hormone-refractory prostate cancer patients (n = 809). We determined anchor-based differences using Karnofsky Performance Status (KPS), bone alkaline phosphatase (BAP), hemoglobin, time to disease progression (TTP), adverse events (AE), and survival. One-third and one-half standard deviation and standard error of measurement (SEM) were used as distribution-based criteria for CMCs. Comparison across baseline FACT-P domains and derived scales [FACT-P total score, Trial Outcome Index (TOI) score, prostate cancer subscale (PCS) score, pain-related score, and FACT Advanced Prostate Symptom Index (FAPSI)] were conducted for KPS, BAP, and hemoglobin using Student's t tests. Twelve-week change scores were compared for TTP, AE, and survival using ANCOVA. RESULTS: CMCs were estimated as 6 to 10 for FACT-P total score, 5 to 9 for FACT-P TOI score, 2 to 3 for FACT-P PCS, 1 to 2 for the 4 PCS pain-related questions, and 2 to 3 for FAPSI. CMCs were also estimated using distribution-based criteria. Kappa statistics were computed to determine the degree of correspondence between the recommended guideline of 1.0 SEM and empirically derived standards. Most of the kappas for health-related quality of life domains and SEM standards had "substantial" to "almost perfect" concordance. CONCLUSIONS: The significant relationship between clinical and quality of life data provides support for the use of CMCs to increase interpretability of FACT-P scores.