James Signorovitch

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

The absence of head-to-head trials is a common challenge in comparative effectiveness research and health technology assessment. Indirect cross-trial treatment comparisons are possible, but can be biased by cross-trial differences in patient characteristics. Using only published aggregate data, adjustment for such biases may be impossible. Although individual patient data (IPD) would permit adjustment, they are rarely available for all trials. However, many researchers have the opportunity to access IPD for trials of one treatment, a new drug for example, but only aggregate data for trials of comparator treatments. We propose a method that leverages all available data in this setting by adjusting average patient characteristics in trials with IPD to match those reported for trials without IPD. Treatment outcomes, including continuous, categorical and censored time-to-event outcomes, can then be compared across balanced trial populations.The proposed method is illustrated by a comparison of adalimumab and etanercept for the treatment of psoriasis. IPD from trials of adalimumab versus placebo (n = 1025) were re-weighted to match the average baseline characteristics reported for a trial of etanercept versus placebo (n = 330). Reweighting was based on the estimated propensity of enrolment in the adalimumab versus etanercept trials. Before matching, patients in the adalimumab trials had lower mean age, greater prevalence of psoriatic arthritis, less prior use of systemic treatment or phototherapy, and a smaller mean percentage of body surface area affected than patients in the etanercept trial. After matching, these and all other available baseline characteristics were well balanced across trials. Symptom improvements of ≥75% and ≥90% (as measured by the Psoriasis Area and Severity Index [PASI] score at week 12) were experienced by an additional 17.2% and 14.8% of adalimumab-treated patients compared with the matched etanercept-treated patients (respectively, both p < 0.001). Mean percentage PASI score improvements frombaseline were also greater for adalimumab than for etanercept at weeks 4, 8 and 12 (all p < 0.05). Matching adjustment ensured that this indirect comparison was not biased by differences in mean baseline characteristics across trials, supporting the conclusion that adalimumab was associated with significantly greater symptom reduction than etanercept for the treatment of moderate to severe psoriasis.

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.

Pulmonary Medication Adherence and Health-care Use in Cystic Fibrosis

BACKGROUND Poor treatment adherence is common in cystic fibrosis (CF) and may lead to worse health outcomes and greater health-care use. This study evaluated associations of adherence to pulmonary medications, age, health-care use, and cost among patients with CF. METHODS Patients with CF aged ≥ 6 years were identified in a national commercial claims database. A 12-month medication possession ratio (MPR) was computed for each pulmonary medication and then averaged for a composite MPR (CMPR) for each patient. The CMPR was categorized as low (< 0.50), moderate (0.50-0.80), or high (≥ 0.80). Annual health-care use and costs were measured during the first and second year and compared across adherence categories by multivariable modeling. RESULTS Mean CMPR for the sample (N = 3,287) was 48% ± 31%. Age was inversely related to CMPR. In the concurrent year, more CF-related hospitalizations were observed among patients with low (event rate ratio [ERR], 1.35; 95% CI, 1.15-1.57) and moderate (ERR, 1.25; 95% CI, 1.05-1.48) vs high adherence; similar associations were observed for all-cause hospitalizations and CF-related and all-cause acute care use (hospitalizations + ED) in the concurrent and subsequent year. Rates of CF-related and all-cause outpatient visits did not differ by adherence. Low and moderate adherence predicted higher concurrent health-care costs by

Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution.

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Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment

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Hypoglycaemia and accident risk in people with type 2 diabetes mellitus treated with non-insulin antidiabetes drugs.

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Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.

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

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Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison of randomized trials.

19,709), respectively, compared with high adherence. CONCLUSIONS Worse adherence to pulmonary medications was associated with higher acute health-care use in a national, privately insured cohort of patients with CF. Addressing adherence may reduce avoidable health-care use.

Comparative Efficacy of Vildagliptin and Sitagliptin in Japanese Patients with Type 2 Diabetes Mellitus A Matching-Adjusted Indirect Comparison of Randomized Trials

Though tobramycin inhalation solution has been used for over a decade to improve lung function and reduce exacerbations in patients with cystic fibrosis (CF), its effects on mortality have not been well‐described. This study aimed to assess the association between use of tobramycin inhaled solution and mortality in patients with CF and chronic Pseudomonas aeruginosa (PA) infection.