An indirect comparison of long-term efficacy of every-2-week dosing vs. recommended dosing of ixekizumab in patients who had static Physician's Global Assessment > 1 at week 12.

BACKGROUND: Long-term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate-to-severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks. METHODS: Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA-P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator. RESULTS: In the IXORA-P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA-P study. CONCLUSIONS: Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA-P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate-to-severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160-mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance. Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks. The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12.

Early effective treatment may protect from cognitive decline in paediatric multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is a critical feature for patients with childhood or juvenile multiple sclerosis (MS). OBJECTIVE: To promote the understanding of CI and to address the impact of different pharmacological treatment strategies on cognitive performance in this patient group. METHODS: A cohort of 19 patients with therapy-naïve or ß-Interferon-treated juvenile MS completed a comprehensive neuropsychological assessment at initial presentation (baseline) and on average 2.5 years later (follow-up). The assessments were complemented with a neuropaediatric examination and conventional cerebral magnetic resonance imaging (MRI). RESULTS: 9 patients (47%) were impaired in at least one test at baseline (z-score <-1.645 compared with age-adjusted normative data), with the highest impairment frequency in the domains processing speed and attention & executive functions. At follow-up a higher impairment frequency was prominent in those patients whose therapy had not been escalated (N = 13, 69% impaired in at least one test), while cognition was preserved or ameliorated in patients whose treatment had been escalated to highly effective drugs (N = 6, 0% impaired) during the observational period. These group differences at follow-up were not attributable to differences regarding demographics, MRI metrics or cognitive performance at baseline. CONCLUSION: Our findings confirm that paediatric MS is associated with considerable CI already in early disease stages. Early administration of highly effective treatment may protect from cognitive decline or alleviate CI in juvenile MS, but larger controlled trials are warranted to confirm these preliminary results.

Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P).

BACKGROUND: Ixekizumab is an interleukin-17A antagonist approved for treatment of moderate-to-severe plaque psoriasis with a recommended 160-mg starting dose, then 80 mg every 2 weeks (Q2W) to week 12, and every 4 weeks (Q4W) thereafter. OBJECTIVE: To evaluate continuous Q2W dosing over 52 weeks. METHODS: In this phase III, multicentre, double-blinded, parallel-group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at week 52 in patients with moderate-to-severe plaque psoriasis randomized at a 2 : 1 : 1 ratio to continuous Q2W (n = 611), continuous Q4W (n = 310) or dose adjustment per protocol (Q4W/Q2W, n = 306), each with a 160-mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23?5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression. RESULTS: Co-primary end points were met at week 52: Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85·9% and 79·0%, respectively (P = 0·006), and static patient global assessment 0/1 responses for Q2W and Q4W dose groups were 78·6% and 70·6%, respectively (P = 0·005). Treatment-emergent and serious adverse events were comparable across dose groups. CONCLUSIONS: Ixekizumab Q2W had higher efficacy at week 52 than ixekizumab Q4W, with no increase in safety events.

Symptom report and treatment experience of hypogonadal men with and without type 2 diabetes in a United States health plan.

BACKGROUND: Although hypogonadism (HG) is interrelated with type 2 diabetes mellitus (T2DM), there is little information about men's experiences with HG, T2DM, and testosterone replacement therapy (TRT). We examined symptoms and TRT use among men with HG, with and without T2DM, who received care within a single United States health plan. METHODS: Men aged ≥ 18 years with HG, with and without T2DM, were identified from the 2008 to 2010 Reliant Medical Group electronic medical record database. Surveys responses compared by T2DM status using chi-square or Wilcoxon rank sum tests. RESULTS: A total of 93 men were included (19 with HG and T2DM, 74 with HG only). Men with both HG and T2DM were more frequently treated for their HG by an endocrinologist (52.6%), compared with men with HG only (28.4%, p = 0.058). Erectile dysfunction (ED) was the primary reason for seeking care among all surveyed men, although men with HG and T2DM reported experiencing ED more often (94.7%) than men with HG only (46.0%, p < 0.0001). Additional reasons for seeking care were similar between cohorts and included loss of energy and decreased sex drive. Most men (88.2%) reported using TRT, primarily as injection or gel formulations. Discontinuation of TRT was reported slightly more frequently by men with HG and T2DM (68.4%), compared with men with HG only (55.4%, p > 0.05). CONCLUSIONS: This study provides information about symptoms and TRT utilisation among HG men with and without T2DM. Men with HG only were less likely than those with both HG and T2DM to report that they were currently experiencing key symptoms compared with when they were first diagnosed, regardless of TRT utilisation, and were less likely to report ED as a current symptom.

Experiences and treatment patterns of hypogonadal men in a U.S. health system.

OBJECTIVE: To examine self-reported experiences with hypogonadism (HG) and patterns of testosterone replacement therapy (TRT) in men seeking care in a U.S. healthcare system. METHODS: Men ≥ 18 years old with HG were identified from the 2008-2010 Reliant electronic medical records database. Surveys, including validated instruments for measuring symptoms of HG, were collected and evaluated for demographic and behavioural data. RESULTS: Surveys were mailed to 133 men with HG in 2012. Of the 107 surveys returned, 95 were included in the final analysis. Most respondents were Caucasian (90.5%). Men reported developing symptoms of HG, as well as being diagnosed, at a median age of 50 years. The most common symptoms reported as reasons for seeking treatment were erectile dysfunction (66.3%), fatigue (59.0%) and decreased sex drive (57.9%). These continued to be the most bothersome symptoms at the time of the survey regardless of whether the patient received treatment, although men who were currently taking TRT reported less severe symptoms. Approximately 88% of men reported taking TRT at some point, with 61.9% on therapy at the time of the survey. CONCLUSIONS: This study examined men's experiences with HG, including symptoms, quality of life, and treatments. Some symptoms continued despite treatment, and therapy was discontinued at a high rate, which men generally attributed to cost and perceptions of efficacy. In light of this lack of adherence, patients may benefit from appropriate expectation setting regarding reasonable timelines for symptom improvement, the strengths and challenges of various TRT formulations, the importance of adherence and the benefits and risks of TRT.