In a 12-week, multicentre, randomised, double-blind trial «Buttgereit F, Doering G, Schaeffler A ym. Efficacy...»1, 288 patients with active rheumatoid arthritis were randomly assigned to either a modified-release prednisone tablet (n = 144) or to an immediate-release prednisone tablet (n = 144). The modified-release tablet was taken at bedtime and prednisone was released with a delay of 4 h after ingestion. This treatment was compared with morning administration of immediate-release prednisone as an active comparator.
The mean relative change in the primary outcome measure i.e., duration of morning stiffness of the joints from baseline to end of treatment was significantly higher with modified-release prednisone than with immediate-release prednisone (-22.7 vs -0.4 %; difference = 22.4 %; 95 % CI 0.49–44.30; p = 0.045). The absolute difference between the treatment groups was 29.2 min (95 % CI -2.59–61.9) in favour of modified-release prednisone (p = 0.072). The safety profile did not differ between treatments.
A 9-month open-label extension of the trial «Buttgereit F, Doering G, Schaeffler A ym. Targetin...»2previous investigated the long-term safety and efficacy of prednisone chronotherapy with a novel modified-release (MR) prednisone for up to 12 months. Of 288 patients with rheumatoid arthritis originally randomised to MR or immediate-release (IR) prednisone, 249 continued with prednisone chronotherapy (2–10 mg/day) in the 9-month open-label extension.
After 6 months of treatment, morning stiffness of the joints (MS) was reduced in the IR/MR group by 54 % and in the MR/MR group by 56 %. MS reduction after 12 months was 45 % (IR/MR group) and 55 % (MR/MR group). Disease activity measured by DAS28 was reduced from 5.8 to 4.8 (MR/MR group) and 4.9 (IR/MR group), respectively. Adverse events did not differ from the known profile of low-dose prednisone.
In a 12-week, double-blind, placebo controlled study «Buttgereit F, Mehta D, Kirwan J ym. Low-dose predn...»3, 350 patients with active RA were randomised 2:1 to receive modified-release (MR) prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. MR prednisone plus DMARD treatment produced higher response rates for ACR20 (48 vs 29 %, p < 0.001) and ACR50 (22 vs 10 %, p < 0.006) and a greater median relative reduction from baseline in morning stiffness (55 vs 35 %, p < 0.002), in severity of RA (Disease Activity Score 28) (p < 0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score) (p = 0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p < 0.001 at week 12 than placebo plus DMARD treatment.
In an open-label observational study «Cutolo M, Iaccarino L, Doria A ym. Efficacy of the...»4, 950 RA outpatients (mean age 57 + 13 years; 75 % females) treated with GCs and DMARDs (83.7 % methotrexate, 10.5 % leflunomide; 15.8 % biologics) were switched from IR-prednisone or 6-methyl (6M)-prednisolone to low-dose MR-prednisone and followed for 4 months. Morning stiffness duration (MS), pain intensity (numerical rating scale [NRS], 0–10), patient and physician global assessment (GA, 0–10 scale) and disease activity score (DAS28) were assessed at baseline, 2 and 4 months.
513 patients were switched to MR-prednisone from IR-prednisone (9.4 + 5.4 mg) and 437 from 6M-prednisolone (6.7 + 3.7 mg). Among 920 patients (96.8 %) completing 4-months' MR-prednisone treatment, MS decreased from 58 + 37 min at T1 to 32 + 24 min at endpoint (p < 0.001); NRS pain intensity reduced from 5.4 + 1.8 to 3.5 + 1.4 (p < 0.001), and patient and physician GA scores improved from 5.4 + 1.7 to 3.5 + 1.4 and 5.1 + 1.7 to 3.3 + 1.4, respectively (p < 0.001). DAS28 score decreased from 4.2 + 1.4 to 3.3 + 1.2 (p < 0.001). Mean daily MR-prednisone dosage decreased from 8.2 mg to 6.7 mg between baseline and endpoint.
Suositus käyttää modified release kortikoiditabletteja on heikko, koska näyttö pitkäaikaisesta hyödystä puuttuu ja hoito on hinnakasta.