BackgroundThe PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol (LDL‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone.Methods and ResultsPatients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL‐C target levels were not met. The primary efficacy endpoint was LDL‐C percentage change from baseline to W24. Mean baseline LDL‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P<0.0001 versus placebo). In total, 63.9% and 70.3% of alirocumab‐treated patients achieved their LDL‐C targets at W24. Treatment‐emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection‐site reactions among the most common treatment‐emergent adverse events.ConclusionsAlirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL‐C.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023879.

Kidney involvement in Sjögren's syndrome (SS) including renal tubular disorders are well recognized but little is known about frequency and extent of such dysfunction in the general population of patients with primary SS, due to a lack of group studies. We studied 27 patients with primary SS and without other possible causes of tubular dysfunction. Increased urinary beta 2M excretion, due to proximal tubular dysfunction, was present in 26% of patients. Inadequate urine acidification after oral NH4 Cl, proving distal tubular dysfunction, was found in 12% of the patients studied. Concentrating ability, tested by thirst, was decreased in 44% of patients studied. Abnormal renal tubular tests correlated with presence of ANA (p = 0.05) but not with other clinical parameters. In conclusion demonstrable renal tubular dysfunctions occur in over half the patients with primary SS. Literature concerning this subject is discussed.

Serum levels and 24-hour urinary excretion of beta 2-Microglobulin (beta 2-M) was investigated in a group of 101 patients with rheumatoid arthritis (RA), without any other signs of renal disease in past or present, and in a comparable control group. Elevated 24-hour urinary beta 2-M excretion, due to renal proximal tubules dysfunction, was observed in 19% of the patients and not in the control group. There was a significant correlation with clinical signs of extra-articular RA. It is postulated that the observed increase may be an early symptom of renal involvement in RA. Elevated serum beta 2 levels, corrected for glomerular filtration rate, were observed in 44% of the RA patients and only in 3% of the control group and correlated with clinical signs of a more severe RA, as well as with increased 24-hour urinary beta 2-M excretion.

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