Corticosteroids are the drugs of choice for many rheumatic diseases, including vasculitis. There is controversy concerning the route of administration. If there is active vasculitis and the blood vessels of the gastrointestinal tract are affected, there may be impaired absorption of oral corticosteroids.
To determine whether patients with active vasculitis, as evidenced by elevated neopterin, von Willebrand factor antigen (vWFAg), and abnormal nailfold capillaroscopy (NFC), have equivalent bioavailability of oral prednisolone (OP) compared with intravenous methylprednisolone (IVMP).
Six patients with rheumatic disease involving vasculitis (juvenile dermatomyositis, scleroderma, or overlap syndrome), four females, two males (mean age 17.8 years [range 11–27]; one Hispanic, one Asian, one African American, three Caucasian) were admitted to an IRB-approved Clinical Research Center protocol. After fasting overnight, they received 50 mg/m2 OP on day 1, and 50 mg/m2 IVMP on day 2. Baseline blood samples were drawn 1 min prior to each corticosteroid dose (neopterin and vWFAg on day 1; prednisolone level on day 2), at 5, 15, 30, 45, 60, and 90 min and then hourly from the second through the eighth hour. After extraction, samples were analyzed by reverse-phase HPLC for the levels of prednisolone (day 1 samples) and methylprednisolone (day 2 samples). The area under the serum OP or IVMP concentration versus time curve (AUC) was determined using the trapezoid method. NFC images were evaluated by freeze-frame video microscopy as previously described.
See Table 1. There was a positive correlation coefficient for ΔAUC (IVMP–OP) with vWFAg, neopterin, and NFC avascularity score of 0.74, 0.68, and 0.66, respectively; there was a negative correlation coefficient for ΔAUC (IVMP–OP) with NFC end row capillary/mm of 0.64. Linear regression analysis of ΔAUC (IVMP–OP) and vWFAg approached statistical significance (P = 0.08) and given that only six patients were evaluated this may be clinically significant.
Patients with elevated vWFAg, neopterin, and/or evidence of abnormal nailfold by capillaroscopy may have decreased absorption of OP. We speculate that this observation can provide the rationale for the greater efficacy of IVMP in the therapy of patients with active vasculitis of rheumatic disease. More patients will be evaluated to further establish the use of IVMP over OP in active vasculitis.
Supported in part by grant M01 RR-00048 from the National Center for Research Resources, NIH, Northwestern GCRC, and the Marlene Apfelbaum Memorial Foundation.