A briefing of the latest findings in the literature, including:
Cardiovascular Disease Event Rates in Psoriasis Patients Treated With Systemic Anti-inflammatory Drugs Lower Than Other Therapies
Psoriasis is associated with cardiovascular morbidity and mortality. Systemic anti-inflammatory treatment of patients with severe psoriasis with biologic agents or methotrexate is associated with a lower combined risk for death, myocardial infarction, and stroke than other antipsoriatic therapies, according to research published online on September 11 in the Journal of Internal Medicine.
Ole Ahlehoff, MD, PhD, from the Department of Cardiology at Copenhagen University Hospital in Roskilde, Denmark, and colleagues conducted a real-world study involving 2400 Danish patients with severe psoriasis who were treated with systemic anti-inflammatory drugs, including 693 patients treated with biologic agents and 799 treated with methotrexate, or other therapies including retinoids, cyclosporine, and phototherapy to measure cardiovascular disease event rates. The primary outcome was a composite end point of death, myocardial infarction, and stroke.
Overall, the researchers found that 6.0, 17.3, and 44.5 events per 1000 patient-years occurred in patients treated with biologic agents, methotrexate, and other therapies, respectively. Using the other psoriatic therapies (including retinoids, cyclosporine, and phototherapy) as a reference cohort, the risk for cardiovascular events was lower with biologic agents and methotrexate (hazard ratio, 0.28 and 0.65, respectively).
"In conclusion, in this nationwide study of patients with severe psoriasis, systemic anti-inflammatory treatment with biological agents or methotrexate was associated with reduced cardiovascular disease event rates," the authors write. "Further studies are needed to confirm these findings and evaluate their clinical implications."
Source: ©2012 HealthDay, with additional information from Journal of Internal Medicine (Ahlehoff O, Skov L, Gislason G, et al. Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs: a Danish real-world cohort study [published online ahead of print September 11, 2012]. J Intern Med. doi:10.1111/j.1365-2796.2012.02593.x).
Leflunomide Therapy for Psoriatic Arthritis Is Effective and Safe
Leflunomide is effective and well-tolerated for the treatment of patients with psoriatic arthritis (PsA) in daily clinical practice, according to a study published online October 6 in Arthritis Care & Research. It also has beneficial effects on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease.
To assess the effectiveness and safety of leflunomide, Frank Behrens, MD, from the Division of Rheumatology at Johann Wolfgang Goethe-University in Frankfurt, Germany, and colleagues conducted a prospective, multinational, 24-week observational study involving 514 adult patients (mean age, 50.7 years; mean disease duration, 6.1 years) with active PsA who began treatment with leflunomide. The Psoriatic Arthritis Response Criteria (PsARC) was used to assess response.
In the primary effectiveness analysis, the researchers found that at 24 weeks, 380 of 440 patients (86.4%) achieved a PsARC response. Tender and swollen joint scores and counts improved significantly, as well as patient and physician global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. The rate of treatment discontinuation was 12.3%. Adverse drug reactions occurred in 62 patients (12.1%), with 3 considered serious (2 increased liver enzymes and 1 hypertensive crisis).
"On the basis of these data, we conclude that leflunomide is effective and has a favorable safety profile in the therapy of PsA in daily clinical practice," the authors write. "Its ability to alleviate joint, skin, and other disease manifestations; manageable safety profile; and relatively low price make leflunomide a valuable option for the treatment of PsA."
Source: ©2012 HealthDay, with additional information from Arthritis Care & Research (Behrens F, Finkenwirth C, Pavelka K, et al. Leflunomide in psoriatic arthritis: results from a large European prospective observational study [published online ahead of print October 6, 2012]. Arthritis Care Res. doi:10.1002/acr.21848).
Metastatic Melanoma Patients Respond to Combination Therapy With Dabrafenib Plus Trametinib
For patients with metastatic melanoma and BRAF V600 mutations, combination therapy with a selective BRAF inhibitor (dabrafenib) and a selective mitogen-activated protein kinase (MEK) inhibitor (trametinib) is tolerable and active, according to a study published online on September 29 in the New England Journal of Medicine.
Keith T. Flaherty, MD, from the Massachusetts General Hospital Cancer Center in Boston, and colleagues conducted an open-label phase 1 and 2 study involving 247 patients with metastatic melanoma and BRAF V600 mutations. The pharmacokinetic activity and safety of oral dabrafenib and trametinib was assessed in 85 patients, and 162 patients were randomly allocated to receive either dabrafenib plus trametinib or dabrafenib monotherapy. The primary end points included incidence of cutaneous squamous cell carcinoma, survival free of melanoma progression, and response; secondary end points included overall survival and pharmacokinetic activity.
The researchers identified dose-limiting toxic effects infrequently in patients receiving combination therapy (150 mg of dabrafenib and 2 mg of trametinib [combination 150/2]). Cutaneous squamous cell carcinoma occurred in more patients receiving monotherapy (19%) than in those receiving the combination 150/2 (7%)(P=.09). Pyrexia was more common in the combination group (71%) versus the monotherapy group (26%). The median progression-free survival was 9.4 months in the combination group versus 5.8 months in the monotherapy group (hazard ratio for progression or death, 0.39). The rate of complete or partial response was significantly higher in the combination group versus the monotherapy group (76% vs 54%; P=.03).
"Dabrafenib and trametinib were safely combined at full monotherapy doses," the authors write. "We believe that the combination of dabrafenib and trametinib warrants further evaluation as a potential treatment for metastatic melanoma with BRAF V600 mutations and other cancers with these mutations."
Source: ©2012 HealthDay, with additional information from New England Journal of Medicine (Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations [published online ahead of print September 29, 2012]. N Engl J Med. 2012;367:1694-1703).
Rapidly Progressive Alopecia Shows Favorable Prognosis Regardless of Therapy Employed
Patients with rapidly progressive alopecia areata (RPAA) tend to show favorable prognosis regardless of treatment selected, according to research published online September 24 in the Journal of the American Academy of Dermatology.
Masaki Uchiyama, MD, from the Department of Dermatology at the Tokyo Medical University in Japan, and colleagues retrospectively analyzed 1030 patients diagnosed with alopecia areata (AA) for 3 years.
The researchers found that patients with regenerated vellus hairs showed a significantly higher improvement or cure rate regardless of AA severity. Lower rates of cure and higher rates of relapse were significantly associated with early onset and lengthy duration. Regardless of treatment utilized, RPAA patients tended to show a good prognosis.
"Our study suggested that there was no statistically significant influence of the initial treatment modalities on the prognosis of AA patients with severe hair loss, including both RPAA and chronic persistent AA," Uchiyama and colleagues conclude. "Recent studies have demonstrated that AA is associated with autoimmunity. However, RPAA patients tend to have a favorable prognosis, and the pathogenesis of curable RPAA is thought to be less associated with the autoimmune system than chronic forms of AA."
Source: ©2012 HealthDay, with additional information from Journal of the American Academy of Dermatology (Uchiyama M, Egusa C, Hobo A, et al. Multivariate analysis of prognostic factors in patients with rapidly progressive alopecia areata [published online ahead of print September 24, 2012]. J Am Acad Dermatol. doi:10.1016/j.jaad.2012.06.006).
Risk For Melanoma Higher in Immunosuppressed Patients
Immunosuppressed patients, particularly organ transplant recipients and lymphoma patients, have approximately a 2-fold or higher risk for developing melanoma, according to research published in the October issue of the Mayo Clinic Proceedings.
Agnieszka W. Kubica and Jerry D. Brewer, MD, of the Mayo Medical School College of Medicine in Rochester, Minnesota, performed a comprehensive review to summarize the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail, including organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS. The authors highlighted melanoma-induced immunosuppression; the role of UV radiation in melanoma development; and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients.
By reviewing studies with large numbers of patients and population-based national or international epidemiologic studies, the researchers found an increase in the incidence of melanoma among immunosuppressed patients. The largest studies showed that transplant recipients and lymphoma patients had an approximately 2-fold or higher risk for developing melanoma and a higher risk for dying from melanoma. Patients with chronic lymphocytic leukemia were 2.8-fold more likely to die from metastatic melanoma.
"How you catch melanoma earlier is to be very aware of your skin," Brewer said in a statement. "These patients with immunosuppression should be looking themselves over head-to-toe once a month, they should be seeing a dermatologist once or twice a year, and if they have a lot of other risk factors, maybe more often than that." The authors concluded that novel therapies could be developed with a better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, which could affect treatment outcomes in these patients.
Source: ©2012 HealthDay, with additional information from Mayo Clinic Proceedings (Kubica AW, Brewer JD. Melanoma in immunosuppressed patients. Mayo Clin Proc. 2012;87:991-1003).