Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis

In this phase III, double-blind, placebo-controlled study, 606 patients with psoriatic arthritis were randomised to intravenous (IV) secukinumab 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab 150 mg (IV→150 mg) or 75 mg (IV→75 mg), or placebo. Patients were stratified by prior anti-TNF (tumour necrosis factor) exposure (71% anti-TNF-naïve). At week 16, placebo-treated patients who had ≥20% reduction in tender and swollen joint count (responders) remained on placebo until week 24; non-responders were re-randomised to secukinumab 150 or 75 mg. The van der Heijde modified total Sharp score (mTSS) was determined at baseline, week 16/24 and week 52.In the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed secukinumab reduced progression at week 24, regardless of prior anti-TNF use; mean change from baseline to week 24 in mTSS in the secukinumab pooled and placebo groups was 0.05 and 0.57, respectively for anti-TNF-naïve patients and 0.16 and 0.58, respectively in anti-TNF-IR patients. Anti-TNF-naïve patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52, irrespective of concomitant methotrexate use. A high proportion of patients showed no progression (≤0.5) with secukinumab from baseline to week 24 (IV→150 mg, 82.3%; IV→75 mg, 92.3%) and from week 24 to week 52 (IV→150 mg, 85.7%; IV→75 mg, 85.8%).Secukinumab inhibited radiographic progression in patients with active psoriatic arthritis through 52 weeks of therapy

Ground-Water Modeling Issues in Ground-Water Development: Model Calibration and Verification

36 pages (includes illustrations and maps). Contains references

Ground-Water Modeling Issues in Ground-Water Development: Types of Models/Choosing the Right Model

26 pages. Contains 3 pages of references

Ground-Water Modeling Issues in Ground-Water Development: Types of Models/Choosing the Right Model

26 pages. Contains 3 pages of references

Erosions and sclerosis on radiographs precede the subsequent development of syndesmophytes at the same site: a twelve-year prospective followup of patients with ankylosing spondylitis

Objective: To analyze whether erosions, sclerosis, and squaring assessed on radiographs precede the development of syndesmophytes in patients with ankylosing spondylitis (AS). Methods: Patients with AS from the Outcome in Ankylosing Spondylitis International Study (OASIS) cohort were followed up for 12 years, with radiographs obtained every 2 years. Two readers (reader 1 and reader 2) scored radiographs according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and recorded abnormalities per vertebral corner. Progression from erosions, sclerosis, or squaring to (bridging) syndesmophytes was investigated using multilevel longitudinal (autoregressive and time-lagged) regression analysis. Interactions with reader and spinal region were investigated. Results: The analysis included 211 patients (71% male, 85% HLA-B27 positive) with a mean SD age of 43 +/- 13 years and a symptom duration of 21 +/- 12 years. A total of 921 radiographs were included, with 20,509 (reader 1) and 20,568 (reader 2) vertebral corners evaluable. Erosions were found in 1% and 2.5%, sclerosis in 0.3% and 1.7%, squaring in 6.5% and 5.1%, and syndesmophytes in 25% and 27%, by reader 1 and reader 2, respectively. The odds ratio for a new syndesmophyte to occur within 2 years at the same vertebral corner if erosions, sclerosis, or squaring were present was 2.0 (95% confidence interval [95% CI] 1.7-2.3) for the cervical and lumbar spine together, 3.1 (95% CI 2.5-3.9) for the cervical spine, and 1.3 (95% CI 1.0-1.6) for the lumbar spine. When vertebral corners with erosions, sclerosis, and squaring were analyzed separately, this effect was statistically significant for erosions and for sclerosis, but not for squaring. Conclusion: Erosions and sclerosis occur infrequently in patients with AS, but when they do occur, they precede the development of a new syndesmophyte, and are therefore important to assess