Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study.

Objective: This study aimed to report end-of-study results on efficacy and safety of secukinumab 150 mg through 5 years in patients with ankylosing spondylitis (AS; MEASURE 1 extension trial (NCT01863732)). Methods: After the 2-year core trial, 274 patients receiving subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) every 4 weeks were invited to enter the 3-year extension study. Dose escalation from 75 to 150 mg (approved dose) was allowed at or after week 156 based on the judgement of the treating physician. Assessments at week 260 (5 years) included Assessment of SpondyloArthritis international Society (ASAS) 20/40 and other efficacy outcomes. Data are presented as observed. Safety assessment included all patients who received ≥1 dose of study treatment. Results: Of the 274 patients who entered the extension study, 84% (230/274) completed 5 years of treatment. ASAS20/40 responses were 78.6/65.2%, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response was 63.4% and mean (±SD) BASDAI total score was 2.6±1.76 with secukinumab 150 mg at 5 years. Improvements in efficacy outcomes were sustained through 5 years. A total of 82 patients on secukinumab 75 mg (56.2%) had their dose escalated to 150 mg after week 168; ASAS40, ASAS-PR, ASAS 5/6 and BASDAI50 responses were improved in patients whose dose was escalated from secukinumab 75 to 150 mg. Secukinumab was well tolerated with a safety profile consistent over the course of the study. Conclusions: Secukinumab 150 mg provided sustained efficacy across multiple domains of AS with a favourable and consistent safety profile through 5-year treatment. Over 50% of patients required dose escalation from 75 to 150 mg and efficacy improved in these patients.

Secukinumab in the treatment of psoriatic arthritis: efficacy and safety results through 3 years from the year 1 extension of the randomised phase III FUTURE 1 trial.

OBJECTIVE: To assess the long-term (3 year) efficacy and safety of secukinumab in patients with active psoriatic arthritis (PsA) in the extension phase of the FUTURE 1 study (NCT01892436). METHODS: Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab 150 or 75 mg entered a 3-year extension phase. Results are presented for key efficacy and safety endpoints at week 156. RESULTS: In total, 460 patients entered the extension study; 308 patients originally randomised to secukinumab were assessed for efficacy. Sustained improvements in all efficacy endpoints were achieved with secukinumab through week 156. Overall, 76.8%/54.9% (secukinumab 150 mg) and 65.2%/39.0% (secukinumab 75 mg) of patients achieved an American College of Rheumatology (ACR) 20/50 response (multiple imputation data); ACR20 responses were sustained irrespective of previous anti-tumour necrosis factor exposure. Improvements in quality of life and physical function were also sustained through week 156. Radiographic results (observed data; van der Heijde modified total Sharp score (mTSS)) showed that 78.1% (secukinumab 150 mg) and 74.8% (secukinumab 75 mg) of patients had no radiographic progression (≤0.5 increase in mTSS) through week 156. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years (secukinumab 150/75 mg) were serious infections (1.7/1.6), Candida infections (1.4/0.7), Crohn's disease (0/0.3), ulcerative colitis (0/0.3) and major adverse cardiac events (0.3/0.8). CONCLUSION: Subcutaneous secukinumab provided sustained improvements in the signs and symptoms, quality of life and physical function of patients with active PsA with low rate of radiographic disease progression through 3 years. Secukinumab was well tolerated with no new safety signals.

Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 3-year results from the phase III trial, MEASURE 2.

BACKGROUND: Secukinumab treatment has previously been shown to significantly improve the signs and symptoms of active ankylosing spondylitis (AS), with responses sustained through 2 years. Here, we report the long-term (3 years) efficacy and safety of secukinumab in the MEASURE 2 study. METHODS: MEASURE 2 (NCT01649375) is a 5-year phase III, randomised, double-blind, double-dummy, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of subcutaneous loading and maintenance dosing of secukinumab in adult subjects with active AS. Subjects were randomised to receive subcutaneous secukinumab 150 mg, 75 mg or placebo at baseline, weeks 1, 2 and 3 and every 4 weeks from week 4. At week 16, placebo-treated subjects were rerandomised to receive secukinumab 150/75 mg. RESULTS: Retention rates were high during weeks 16-156 and were 86% and 76% for secukinumab 150 and 75 mg, respectively. Secukinumab 150 mg provided sustained improvements in the Assessment of Spondyloarthritis International Society ASAS 20/40 response rates at week 156 (70.1%/60.9%) compared with week 52 (74.2%/57.0%); however, there was a slight decrease for secukinumab 75 mg (54.3%/37.0% vs 62.5%/43.2%, respectively). Sustained improvements were observed in all other end points, including Bath Ankylosing Spondylitis Disease Activity Index, AS Disease Activity Score with C reactive protein inactive disease, ASAS 5/6, Short Form-36 Physical Component Summary and ASAS partial remission. Clinical benefits were observed regardless of prior exposure to anti-tumour necrosis factor agents. The safety profile remained favourable and was consistent with previous reports. CONCLUSIONS: This study showed sustained improvement through 3 years in signs, symptoms and physical function in subjects with AS. Retention rates were high and secukinumab was well tolerated, with a favourable safety profile.

Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study.

OBJECTIVES: To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice. METHODS: This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months. RESULTS: 234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy. CONCLUSIONS: Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.

Dietary consumption patterns and laryngeal cancer risk.

We conducted a case-control study to investigate the effect of diet on laryngeal carcinogenesis. Our study population was made up of 140 participants-70 patients with laryngeal cancer (LC) and 70 controls with a non-neoplastic condition that was unrelated to diet, smoking, or alcohol. A food-frequency questionnaire determined the mean consumption of 113 different items during the 3 years prior to symptom onset. Total energy intake and cooking mode were also noted. The relative risk, odds ratio (OR), and 95% confidence interval (CI) were estimated by multiple logistic regression analysis. We found that the total energy intake was significantly higher in the LC group (p < 0.001), and that the difference remained statistically significant after logistic regression analysis (p < 0.001; OR: 118.70). Notably, meat consumption was higher in the LC group (p < 0.001), and the difference remained significant after logistic regression analysis (p = 0.029; OR: 1.16). LC patients also consumed significantly more fried food (p = 0.036); this difference also remained significant in the logistic regression model (p = 0.026; OR: 5.45). The LC group also consumed significantly more seafood (p = 0.012); the difference persisted after logistic regression analysis (p = 0.009; OR: 2.48), with the consumption of shrimp proving detrimental (p = 0.049; OR: 2.18). Finally, the intake of zinc was significantly higher in the LC group before and after logistic regression analysis (p = 0.034 and p = 0.011; OR: 30.15, respectively). Cereal consumption (including pastas) was also higher among the LC patients (p = 0.043), with logistic regression analysis showing that their negative effect was possibly associated with the sauces and dressings that traditionally accompany pasta dishes (p = 0.006; OR: 4.78). Conversely, a higher consumption of dairy products was found in controls (p < 0.05); logistic regression analysis showed that calcium appeared to be protective at the micronutrient level (p < 0.001; OR: 0.27). We found no difference in the overall consumption of fruits and vegetables between the LC patients and controls; however, the LC patients did have a greater consumption of cooked tomatoes and cooked root vegetables (p = 0.039 for both), and the controls had more consumption of leeks (p = 0.042) and, among controls younger than 65 years, cooked beans (p = 0.037). Lemon (p = 0.037), squeezed fruit juice (p = 0.032), and watermelon (p = 0.018) were also more frequently consumed by the controls. Other differences at the micronutrient level included greater consumption by the LC patients of retinol (p = 0.044), polyunsaturated fats (p = 0.041), and linoleic acid (p = 0.008); LC patients younger than 65 years also had greater intake of riboflavin (p = 0.045). We conclude that the differences in dietary consumption patterns between LC patients and controls indicate a possible role for lifestyle modifications involving nutritional factors as a means of decreasing the risk of laryngeal cancer.

Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: a pilot study in 15 patients.

PURPOSE: To assess the safety and to conduct a preliminary assessment of efficacy of intravitreal infliximab, an anti-tumor necrosis factor antibody, for sight-threatening relapsing uveitis in Behçet disease. DESIGN: Prospective, noncomparative, interventional pilot study. METHODS: A single intravitreal injection of infliximab (1 mg/0.05 mL) was given to 15 patients with relapsing posterior uveitis at the onset of a unilateral attack. Best-corrected visual acuity, anterior chamber cells, vitreous haze, and posterior eye segment inflammation were assessed at baseline and at 1, 7, 14, and 30 days after treatment. RESULTS: Ocular or extra-ocular side effects were not observed. Baseline best-corrected visual acuity (mean logarithm of minimal angle of resolution, 0.74; range, 0.15 to 1.7) improved significantly by day 7 and continued to improve through day 30 after infliximab (mean, 0.30; P < .0001). Profound decreases in anterior chamber cells and vitreous haze (both P < .0001), as well as beneficial effects in retinal vasculitis (P = .0001) and retinitis (P = .001) were evident through day 30. Cystoid macular edema persisted in 9 of 11 eyes affected, but central macular thickness decreased from a baseline mean of 434 to 309 mm at the end of follow-up (P < .0001). Lack of systemic treatment at baseline in 4 patients or background immunosuppressive medications, which remained unchanged during follow-up, did not influence significantly these responses; additional treatment was not required. CONCLUSIONS: These findings suggest that intraocularly produced or acting tumor necrosis factor, or both, is crucial in Behçet disease-associated relapsing uveitis and that intravitreal infliximab should be considered when systemic administration is not feasible or contraindicated. Further studies may identify patients for whom intravitreal infliximab is preferable to systemic treatment.