The ITT population included 306 patients (100 PBO; 102 atacicept 75 mg; 104 atacicept 150 mg). There was a trend towards improved SRI-4 response with atacicept vs PBO at week 24 (p=ns) (primary analysis; screening visit as baseline, BL) ( Table 1 ). In a prespecified sensitivity analysis using study day 1 as BL, a significantly larger proportion of patients on atacicept achieved SRI-4 response at week 24: PBO, 41%; atacicept 75 mg, % (OR ) p=; atacicept 150 mg, % (OR ) p=. In predefined subpopulations with high disease activity (HDA; SLEDAI-2K ≥10, n=158), serologically active (SA) disease (dsDNA antibody-positive and low complement, n=84), or both (HDA SA, n=69), enhanced improvements in SRI-4 and SRI-6 response rates were seen with atacicept vs PBO ( Table 1 ). SRI-6 response rates in HDA patients were significantly greater with atacicept 150 mg vs PBO at weeks 8, 16 and 24 ( Figure 1 ). In HDA patients, severe flare was significantly reduced by atacicept 75 mg (BILAG A HR ; p=; SLEDAI flare index [SFI] HR ; p=) and 150 mg (BILAG A HR ; p=; SFI HR ; p=). In the ITT population, BILAG A flare was significantly reduced vs PBO with atacicept 75 mg (p=), and severe SFI flare reduced with 150 mg (p=). Atacicept was associated with increased serum complement C3/C4, and decreased IgG, IgM, IgA, and anti-dsDNA antibodies over time. Rates of AEs were similar between groups. Compared with placebo, the risks of SAEs and serious/severe infections were not increased with atacicept ( Table 2 ). Conclusion:
Results: 11 adults eachreceived anabasum and PBO (N = 22). Demographic and disease characteristicswere similar in both cohorts. Both cohorts had mean CDASI activity scores inthe severe range (33-35) despite immunosuppressants (19/22 subjects). Anabasum subjects had clinically meaningful improvement inCDASI activity scores with mean reduction ≥ 5 points at all visits after4 weeks. Improvement had statistical significance at end of study (Fig. 1, P =, 2-sided MMRM) that first became apparent after 4 weeks. Anabasum provided greater improvement than placebo in CDAIdamage index, patient-reported global skin disease and overall diseaseassessments, skin symptoms including photosensitivity and itch, fatigue, sleep,pain interference with activities, pain, and physical function (examples in ). Improvements in secondary efficacy outcomes reached statisticalsignificance (P ≤ , 1-sided MMRM) at multiple visits after week 4(Fig. 1). There were no serious, severe or unexpected adverse events (AEs)related to anabasum. Tolerability of anabasum was excellent with no studydrop-outs. Subjects in the anabasum cohort had numerically more mild AEs thanplacebo subjects (29 vs. 19) and fewer moderate AEs (4 vs. 7). AEs in ≥3 subjects in any cohort were diarrhea, dizziness (lightheadedness), fatigueand dry mouth.
Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.
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