Prednisone

Data for this study were acquired from a recently completed placebo-controlled randomized trial of rosiglitazone for mild to moderately active ulcerative colitis (clinicaltrials.gov #NCT00065065) which has been described in greater detail previously.7 (link) The trial used a slight modification of the Mayo score to assess disease activity (Table 1). Specifically, the bleeding component as described in the Mayo index was modified such that a score of 3 required both visible blood in 50% or more of bowel movements and at least some bowel movements with blood alone.
The study included 105 patients with mild to moderately active disease defined as a total DAI score of 4 to 10, inclusively. Patients were randomized in a 1:1 ratio to receive either rosiglitazone 4 mg or placebo twice daily for 12 weeks. Disease activity was measured at randomization and every four weeks thereafter until week 12, however lower endoscopy was only completed at week 0 and week 12, such that only a partial Mayo score (9 point scale that excludes the endoscopic appearance of the mucosa) could be calculated at the interim visits. In the very early accrual period of the study, a follow-up visit was included at week 2. Without knowledge of the response rates in either arm, the Data and Safety Monitoring Board (DSMB) requested that the week 2 follow-up evaluation be eliminated with the hopes of minimizing the placebo response rate and maximizing recruitment and retention.6 (link), 8 (link), 9 (link) Eighteen patients completed the week 2 follow-up visit.
During the course of the study, patients could be treated with other conventional medications used to treat active ulcerative colitis including mesalamine, oral corticosteroids, immunomodulators, or topical therapies (mesalamine or corticosteroids) at stable doses. Use of corticosteroids at doses greater than 20mg per day of prednisone or the equivalent was an exclusion criterion. Steroid tapering was not permitted during the study.
In anticipation of this sub-study, at each visit we also included questions about change in disease activity compared to the previous visit and compared to the randomization visit on a global seven-point scale (Table 2). The choices included much better, moderately better, a little better, unchanged, a little worse, moderately worse, and much worse. Patients also graded their current disease activity at each visit on a 6 point Likert scale – perfect, very good (minimal symptoms), good (only mild symptoms), moderately active, moderately severe, or severe. Data on quality of life were measured with the Inflammatory Bowel Disease Questionnaire (IBDQ) authored by Dr. Jan Irvine under license from McMaster University, Hamilton, Canada.10 (link)

In this phase 3, multicenter, randomized, double-blind, placebo-controlled trial, patients with SLE on SOC therapy were assigned to receive placebo, or belimumab 1 or 10 mg/kg by intravenous (IV) infusion over 1 hour on days 0, 14, and 28, and every 28 days through week 72. While the initiation of an immunosuppressive (IS) drug was prohibited during the trial, the addition of a new antimalarial (AM) drug and dose increases of concomitant IS or AM drugs were permitted until week 16. After week 16, however, the maximum doses of IS or AM drugs could be no greater than the higher of the baseline or week-16 dose. For corticosteroids, any dose was permitted through week 24; thereafter through week 44, the dose had to be within 25% or 5 mg of baseline. Between weeks 44 and 52, no increase over the higher of the baseline or week-44 dose was permitted. From weeks 52 through 68, the dose had to be within 25% or 5 mg of baseline, and an increase over the higher of the baseline or week-68 dose was prohibited after week 68. Prednisone could be reduced at the discretion of the investigator. As in the companion phase 3 BLISS-52 trial, the addition of a new biologic agent at any time, an inhibitor of the renin-angiotensin system after 4 months, or a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor after 6 months was prohibited; other antihypertensive or lipid-lowering agents were allowed during the study (17 (link)). The Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) (18 (link)), Physician’s Global Assessment (PGA) (18 (link)), British Isles Lupus Assessment Group (BILAG) (19 (link),20 (link)), and SLE Flare Index (SFI) (21 (link)) were evaluated every 4 weeks (except weeks 56 and 64), as were AEs, vital signs, concomitant medications, and laboratory and pregnancy tests.