Sustained long-term benefits of patient support program participation in immune-mediated diseases: improved medication-taking behavior and lower risk of a hospital visit.

BACKGROUND: Patient support programs (PSPs) improve medication-taking behavior in the first 12 months of treatment for patients with immune-mediated diseases, but it is unknown if these benefits are sustained. As immune-mediated diseases continue to increase in prevalence and economic burden, understanding the potential value of PSPs in helping patients adhere to their long-term treatment plan and avoid costly hospital visits is crucial. Launched nationally in 2015, HUMIRA Complete (a PSP for adalimumab patients) provides an opportunity to study long-term effects of PSP participation, including the impact on medication-taking behavior and hospital visits. OBJECTIVE: To evaluate the sustained relationship between PSP participation, long-term medication-taking behavior, and hospital visits. METHODS: A longitudinal, retrospective matched-cohort study was conducted of patients initiating adalimumab between January 2015 and February 2016 with or without enrolling in the PSP, using patient-level data from the HUMIRA Complete PSP linked with Symphony Health claims. The sample included adult, commercially insured patients diagnosed with an indicated disease who were biologic-naive and had data available for ≥ 6 months before and ≥ 12 months after initiating adalimumab. Adherence (proportion of days covered) and hospital visits were assessed at 12, 24, and 36 months for patients with sufficient follow-up data. Multivariable generalized models estimated differences between cohorts, controlling for baseline characteristics and hospital visits. Duration of persistence and time to a hospital visit were compared using Kaplan-Meier analyses. Hazard ratios were estimated using multivariable Cox proportional hazards models. RESULTS: The matched cohort included 2,268 patients (1,134 per cohort), and patient attrition was similar across cohorts. The PSP cohort consistently demonstrated higher adalimumab adherence than the non-PSP cohort at 12 (64.8% vs. 50.1%, P < 0.0001; 29% greater), 24 (49.4% vs. 38.4%; P < 0.0001; 29% greater), and 36 (39.4% vs. 35.1%; P = 0.02; 12% greater) months. PSP participation was associated with a 30% lower hazard of discontinuation (P < 0.0001), and median duration of persistence was 4.8 months longer for the PSP cohort (13.2 vs. 8.4 months; P < 0.0001). The PSP cohort had lower rates of hospital visits at 12 (30% vs. 37%; P < 0.001; 19% lower), 24 (44% vs. 53%; P = 0.01; 17% lower), and 36 (55% vs. 65%; P < 0.01; 16% lower) months, and PSP participation was associated with a 25% lower hazard of a hospital visit (P < 0.0001). Median time to a hospital visit was 10.8 months longer for the PSP cohort (32.7 vs. 21.9 months; P < 0.0001). Findings were consistent across therapeutic areas: hazard of a hospital visit was 28%, 27%, and 37% lower for rheumatology, gastroenterology, and dermatology patients participating in the PSP (all P < 0.05). CONCLUSIONS: Patients with immune-mediated diseases receiving adalimumab and utilizing this PSP had improved long-term medication-taking behavior and lower risk of hospital visits, demonstrating the potential of PSPs to improve patient outcomes and lower the burden to the health care system. DISCLOSURES: Design, study conduct, and financial support for the study were provided by AbbVie Inc., which participated in the interpretation of data, review, and approval of the manuscript. Fendrick has received personal fees from Merck, AstraZeneca, Trizetto, Amgen, Lilly, AbbVie, Johnson & Johnson, and Sanofi; grants from the National Pharmaceutical Council, PhRMA, the Gary and Mary West Health Foundation, the states of New York and Michigan, the Laura and John Arnold Foundation, the Robert Wood Johnson Foundation, and the Agency for Healthcare Research and Quality; and equity in Zansors, Sempre Health, Wellth, and V-BID Health. Brixner has received consulting fees from AbbVie, Novartis, Xcenda, Elevar Therapeutics, Sanofi, UCB Pharma, and the Millcreek Outcomes Group. Rubin has received consulting fees from AbbVie, Abgenomics, Allergan Inc., Amgen, Celgene Corporation, Forward Pharma, Genentech/Roche, Janssen Pharmaceuticals, Merck & Co., Miraca Life Sciences, Mitsubishi Tanabe Pharma Development America, Napo Pharmaceuticals, Pfizer, Salix Pharmaceuticals Inc., Samsung Bioepis, Sandoz Pharmaceuticals, Shire, Takeda, and Target Pharmaceuticals; and research support from AbbVie, Genentech/Roche, Janssen Pharmaceuticals, Prometheus Laboratories, Shire, Takeda, and UCB Pharma. Mease has received grant/research support from AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB; consulting fees from AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, SUN Pharma, and UCB; and has served on the speakers bureau for AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB. Liu has no financial conflict of interest. Davis is an employee of Medicus Economics, which received payment from AbbVie to participate in this research. Mittal is an employee and stockholder of AbbVie. This study used a cohort of patients previously described in Brixner D, Rubin DT, Mease P, et al. Patient support program increased medication adherence with lower total health care costs despite increased drug spending. J Manag Care Spec Pharm. 2019 Jul;25(7):770-79 (doi: 10.18553/jmcp.2019.18443). As such, the sample selection and select baseline characteristics and 12-month outcomes have been published previously; however, the hospital visit outcomes and the longer-term medication-taking behavior outcomes have not been previously published or presented.

Consensus terminology for preclinical phases of psoriatic arthritis for use in research studies: results from a Delphi consensus study.

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.

Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT core outcome set: a meta-research study of trials included in Cochrane reviews.

The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: "physical function," "pain," "spinal mobility," "spinal stiffness," and "patient's global assessment" (PGA). The core set for clinical record keeping further includes the domains "peripheral joints/entheses" and "acute phase reactants," and the core set for DC-ART further includes the domains "fatigue" and "spine radiographs/hip radiographs." The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials.Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and "missing data") should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.

Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in Patients With Psoriatic Disease: A Meta-Epidemiologic Study.

OBJECTIVE: To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease. METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs. RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70-2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64-3.97]). The eligibility criteria "targeted therapy history," "minimum required disease duration," "required negative rheumatoid factor," and "required Classification Criteria for Psoriatic Arthritis criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time-point-of-retention reporting (adaptive trials). CONCLUSION: From this exploratory meta-epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials.

Biologic Therapy for Psoriatic Arthritis.

Biologic medications, therapeutic proteins that inhibit or modulate proinflammatory immune cells and cytokines, have significantly altered clinicians' ability to effectively treat psoriatic arthritis (PsA). The first widely used biologics have been those targeting tumor necrosis factor alpha. Five agents (etanercept, infliximab, adalimumab, golimumab, and certolizumab) have shown significant benefit in all clinical domains of PsA as well as inhibiting progressive joint destruction. Treatment strategies such as treating PsA early in the disease course, treating to target and tight control, use of background methotrexate to reduce immunogenicity, and various cost-saving strategies are all being tested with biologic medicines for PsA.

Pharmacotherapy of fibromyalgia.

There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient's overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the α(2)δ modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient's overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed.

Pharmacologic immunomodulation and cutaneous malignancy in rheumatoid arthritis, psoriasis, and psoriatic arthritis.

OBJECTIVE: It is unclear if skin cancer risk is affected by the use of immunomodulatory medications in rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis (PsA). The purpose of this study is to evaluate and summarize the available data pertinent to this question. METHODS: The English language literature on PubMed was searched with a combination of phrases, including "malignancy," "skin cancer," "squamous cell carcinoma," "basal cell carcinoma," "melanoma," "psoriasis," "psoriatic arthritis," and "rheumatoid arthritis" in addition to the generic names of a variety of common immunomodulatory drugs. Relevant articles were identified and data were extracted. RESULTS: In total, 2218 potentially relevant articles were identified through the search process. After further screening, 20 articles relevant to RA were included. An additional 19 articles relevant to either psoriasis or PsA were included as well. RA may be a risk factor for the development of cutaneous malignancy. Treatment with tumor necrosis factor inhibitors increases the rates of non-melanoma skin cancer (NMSC) in RA and psoriasis. This risk doubles when combination methotrexate therapy is used in RA. Methotrexate may increase the risk of malignant melanoma in patients with RA and the risk of NMSC in psoriasis. Cyclosporine and prior phototherapy significantly increase the risk of NMSC. CONCLUSION: RA may potentiate the risk of cutaneous malignancy and therefore dermatologic screening in this population should be considered. The use of immunomodulatory therapy in RA, psoriasis, and PsA may further increase the risk of cutaneous malignancy and therefore dermatologic screening examinations are warranted in these groups. More careful recording of skin cancer development during clinical trials and cohort studies is necessary to further delineate the risks of immunomodulatory therapy.

Psoriatic arthritis update.

Psoriatic arthritis is an inflammatory arthritis occurring in up to 30% of patients with psoriasis. Its clear distinction from rheumatoid arthritis has been described clinically, genetically, and immunohistologically. Updated classification criteria have been recently derived from a large international study. Key pathophysiologic cellular processes are being elucidated, increasing our understanding of potential targets of therapy. Therapies that target cells, such as activated T cells, and proinflammatory cytokines, such as tumor necrosis factor alpha (TNFalpha), are rational to pursue. Outcome measures have been "borrowed" from rheumatoid arthritis and psoriasis studies. A variety of domains are assessed including joints, skin, enthesium, dactylitis, spine, function, quality of life, and imaging assessment of disease activity and damage. The performance qualities of outcome measures in these various domains is being evaluated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), and improved measures are being developed and validated specifically for psoriatic arthritis. Traditional therapies for psoriatic arthritis have included nonsteroidal anti-inflammatory agents, oral immunomodulatory drugs, topical creams, and light therapy. These therapies have been helpful in controlling both musculoskeletal and dermatologic aspects of the disease, but they may not be fully effective in all disease domains, may eventually show diminished benefit, and may produce treatment-limiting toxicities. In the past several years, use of biologic agents has generally yielded greater benefit across more domains, yielding significant and enduring benefits for clinical manifestations, function, and quality of life, and especially with the anti-TNF agents, inhibition of structural damage. Adverse effects with these agents can be significant but are usually manageable. Cost is also significant, but cost-effectiveness analysis is demonstrating reasonable trade-off between cost and benefit.

Psoriasis and psoriatic arthritis: clinical features and disease mechanisms.

Psoriasis is a chronic skin disorder affecting approximately 1% to 3% of the world's population. A considerable proportion of patients with psoriasis will develop a form of inflammatory arthritis known as psoriatic arthritis whose prevalence is poorly defined. Significant advances have been made in determining the pathophysiology of both of these diseases, with recent findings strongly implicating T cells and inflammatory cytokines such as tumor necrosis factor alpha in their pathogenesis. There exists an increasing array of therapies to benefit both skin and musculoskeletal manifestations. Newer therapies, such as the biologics, are providing more targeted approaches with potentially fewer systemic toxicities, providing control of disease symptoms and inhibiting progressive joint damage in those with arthritis, as well as improving long-term function and quality of life.

Management of psoriatic arthritis: the therapeutic interface between rheumatology and dermatology.

Psoriatic arthritis is an inflammatory arthritis, which occurs in up to 30% of individuals with psoriasis. Dermatologists and other physicians treating psoriasis are in an ideal position to screen for the condition, and with rheumatologists, strategize optimal therapy. Mild skin and joint manifestations may be treated effectively with topical agents, ultraviolet light therapy, and nonsteroidal anti-inflammatory drugs. More severe manifestations of the disease, including progressive peripheral joint damage, spine disease, enthesitis, dactylitis, and severe skin changes, require systemic therapy. Traditional systemic agents include methotrexate, sulfasalazine, and cyclosporine. When these agents are not adequate or not tolerated, new biologic agents, particularly anti-tumor necrosis factor (TNF) compounds, have shown significant and enduring benefit in all disease domains, improvement in quality of life and function, and inhibition of progressive joint damage.

Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment.

Fibromyalgia syndrome (FM) is a common chronic pain condition that affects at least 2% of the adult population in the USA and other regions in the world where FM is studied. Prevalence rates in some regions have not been ascertained and may be influenced by differences in cultural norms regarding the definition and attribution of chronic pain states. Chronic, widespread pain is the defining feature of FM, but patients may also exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headache, and mood disorders. Although the etiology of FM is not completely understood, the syndrome is thought to arise from influencing factors such as stress, medical illness, and a variety of pain conditions in some, but not all patients, in conjunction with a variety of neurotransmitter and neuroendocrine disturbances. These include reduced levels of biogenic amines, increased concentrations of excitatory neurotransmitters, including substance P, and dysregulation of the hypothalamic-pituitary-adrenal axis. A unifying hypothesis is that FM results from sensitization of the central nervous system. Establishing diagnosis and evaluating effects of therapy in patients with FM may be difficult because of the multifaceted nature of the syndrome and overlap with other chronically painful conditions. Diagnostic criteria, originally developed for research purposes, have aided our understanding of this patient population in both research and clinical settings, but need further refinement as our knowledge about chronic widespread pain evolves. Outcome measures, borrowed from clinical research in pain, rheumatology, neurology, and psychiatry, are able to distinguish treatment response in specific symptom domains. Further work is necessary to validate these measures in FM. In addition, work is under way to develop composite response criteria, intended to address the multidimensional nature of this syndrome. A range of medical treatments, including antidepressants, opioids, nonsteroidal antiinflammatory drugs, sedatives, muscle relaxants, and antiepileptics, have been used to treat FM. Nonpharmaceutical treatment modalities, including exercise, physical therapy, massage, acupuncture, and cognitive behavioral therapy, can be helpful. Few of these approaches have been demonstrated to have clear-cut benefits in randomized controlled trials. However, there is now increased interest as more effective treatments are developed and our ability to accurately measure effect of treatment has improved. The multifaceted nature of FM suggests that multimodal individualized treatment programs may be necessary to achieve optimal outcomes in patients with this syndrome.

Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy.

OBJECTIVE: To assess the effects of treatment with prasterone (dehydroepiandrosterone) on bone mineral density (BMD) in female patients with mild to moderate systemic lupus erythematosus (SLE) receiving chronic treatment with glucocorticoids. METHODS: Fifty-five female patients with SLE who had received prednisone (or glucocorticoid equivalent) /= 6 months were treated for 1 year with either prasterone 200 mg/day (n = 24) or placebo (n = 31) in this randomized, double blind trial. Prasterone or placebo was added to each patient's one or more concomitant standard SLE medications, including glucocorticoids, nonsteroidal antiinflammatory drugs, antimalarials, methotrexate, azathioprine, and other immunosuppressives, which were to be maintained at fixed doses for the duration of the study. RESULTS: BMD was significantly improved in patients who received prasterone compared to placebo. At the lumbar spine, there was a mean (SEM) gain in BMD of 1.7 +/- 0.8% in the prasterone group compared to a mean loss in BMD of -1.1 +/- 0.5% in the placebo group (p = 0.003 between groups). For the total hip, mean gain was 2.0 +/- 0.9% in the prasterone group vs a mean loss of -0.3 +/- 0.4% in the placebo group (p = 0.013 between groups). In the prasterone treatment group, the mean gains from baseline at both lumbar spine and hip were statistically significant. CONCLUSION: Prasterone treatment prevented BMD loss and significantly increased BMD at both the lumbar spine and total hip in female patients with SLE receiving exogenous glucocorticoids.

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus.

OBJECTIVE: To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms. METHODS: Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (/=6 weeks prior to enrollment and remain unchanged during protocol treatment. Responders were patients who experienced no clinical deterioration and had improvement or stabilization over the duration of the study in 2 disease activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus Activity Measure) and 2 quality of life measures (patient's global assessment and the Krupp Fatigue Severity Scale). RESULTS: A total of 381 women with SLE were enrolled. Among patients with clinically active disease at baseline (SLEDAI score >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or stabilization without clinical deterioration, as compared with 65 of 146 in the placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and 16%, respectively, of the prasterone group and in 14% and 2%, respectively, of the placebo group (P < 0.05 for both comparisons). However, most cases of acne and hirsutism were mild and did not require withdrawal from therapy. Myalgias and oral stomatitis were reported less frequently in the prasterone group (22% and 15%, respectively) than in the placebo group (36% and 23%, respectively) (P < 0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol, triglycerides, and C3 complement significantly decreased, while levels of testosterone and, to a lesser extent, estradiol increased in the prasterone group. CONCLUSION: In adult women with active SLE, administration of prasterone at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease and was generally well tolerated.

Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVE: Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis. METHODS: One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality-of-life assessments were performed. RESULTS: At 24 weeks, 56 of 95 leflunomide-treated patients (58.9%; 95% confidence interval [95% CI] 48.4-68.9) and 27 of 91 placebo-treated patients (29.7% [95% CI 20.6-40.2]) were classified as responders by the PsARC (P < 0.0001). Significant differences in favor of leflunomide were also observed in the proportions of patients achieving modified American College of Rheumatology 20% improvement criteria, improvement in the designated psoriasis target lesion, and mean changes from baseline in Psoriasis Area and Severity Index scores and quality-of-life assessments. Diarrhea and alanine aminotransferase increases occurred at higher rates in the leflunomide group. No cases of serious liver toxicity were observed. CONCLUSION: Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.