Safety in moderate-to-severe plaque psoriasis patients with latent tuberculosis treated with guselkumab and anti-tuberculosis treatments concomitantly: results from pooled phase 3 VOYAGE 1 & VOYAGE 2 trials.

BACKGROUND: Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new-onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)-23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics. OBJECTIVES: Safety in moderate-to-severe psoriasis patients with LTBI treated with guselkumab (IL-23 inhibitor) and LTBI treatment was evaluated. METHODS: In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo â†’ guselkumab crossover occurred at week 16 and adalimumab â†’ guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab-treated patients receiving and not receiving LTBI treatment. RESULTS: At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab-treated patients without LTBI (LTBI-) through week 100. Two cases of active TB occurred in LTBI- patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI- patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI- patients. CONCLUSIONS: No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long-term treatment with guselkumab was generally well-tolerated through up to 2 years in patients receiving LTBI medications.

Depression and suicidality in psoriasis: review of the literature including the cytokine theory of depression.

Psoriasis can be a socially isolating disease due to debilitating physical symptoms and the stigma patients feel because of the appearance of their skin. Mental health comorbidities such as anxiety, depression and suicidal ideation and behaviour (SIB) are prevalent in patients with psoriasis. Patients with mild psoriasis can experience psychiatric comorbidities; however, disorders such as depression and SIB are more common in patients with severe psoriasis or psoriatic arthritis. Psychiatric disorders can both result from and contribute to progression of psoriasis, suggesting that psoriasis and psychiatric conditions, such as depression, may have overlapping biological mechanisms. Proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are elevated in both psoriasis and depression, indicating that the inflammatory process may be involved in the progression of both diseases. Elevated cytokine levels in the central nervous system cause physiologic and biochemical changes that may contribute to the development of depression. In this review of the literature, we discuss the evidence that supports the association of psoriasis with mental health disorders and the tools used to detect the presence of these comorbidities. Additionally, we review the most prominent hypotheses on the mechanisms by which the inflammatory response and elevated cytokines can cause depression. These results highlight the role that systemic inflammation plays in the various mental health comorbidities associated with psoriasis, including depression and SIB.

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

The impact of PASI 75 and PASI 90 on quality of life in moderate to severe psoriasis patients.

BACKGROUND: It is well known that psoriasis significantly impacts patients' quality of life (QoL). With the introduction of improved treatment modalities with biologic agents, more patients with moderate to severe psoriasis are able to achieve better results as measured by the Psoriasis Area and Severity Index (PASI). PASI 75 indicates a 75% or greater reduction in PASI scores from baseline and is indicative of excellent disease improvement. With newer biologic agents such as secukinumab, ixekizumab and brodalumab, patients are now capable of achieving PASI 90, introducing additional clinical decisions for physicians when considering treatment options. However, little is known regarding how the difference between achieving PASI-75 versus PASI-90 impacts patients' QoL. OBJECTIVES: The purpose of this study was to compare how achieving PASI 75 versus PASI 90 impacts QoL for patients with moderate to severe plaque psoriasis by using validated psychometric instruments that have been widely used in both dermatologic and non-dermatologic settings. METHODS: Two separate open-label clinical trials were conducted to specifically assess QoL in patients with moderate to severe psoriasis on adalimumab or ustekinumab over 24 weeks. In addition to clinical assessments of psoriasis, patients completed two surveys: The Psychological General Well-Being (PGWB) Index and the Dermatology Life Quality Index (DLQI). Changes in total PGWB score and DLQI score at weeks 12 and 24 compared to baseline were compared between groups achieving PASI 75 and PASI 90. RESULTS: There was no statistically significant difference in PGWB scores between patients achieving PASI 75 and patients achieving PASI 90 in the adalimumab treatment group (week 12 p = .21, but there was at week 24 p = .05). There was a statistically significant difference in DLQI between the patients achieving PASI 75 and the patients achieving PASI 90 in the adalimumab treatment group at week 24 (p = .01), but not week 12 (p = .11). There was no statistically significant difference in PGWB scores between patients achieving PASI 75 and patients achieving PASI 90 in the ustekinumab treatment group (week 12 p = .11, week 24 p = .35). There was no statistically significant difference in DLQI between the patients achieving PASI 75 and the patients achieving PASI 90 in the ustekinumab treatment group at week 24 (week 12 p = .49, week 24 p = .11). CONCLUSIONS: There has been tremendous attention surrounding newer biologic agents that can achieve PASI 90 and even PASI 100. Although the results are impressive with regard to physical improvement of psoriasis, there may not be a clinically significant difference in QoL when comparing patients who achieve PASI-75 versus PASI 90.