A systematic review «Gaujoux-Viala C, Nam J, Ramiro S ym. Efficacy of c...»1 of the literature was performed from 2009 until January 2013 about the efficacy of glucocorticoids in early RA. Of 222 hits, five publications relating to four new trials were analysed for efficacy, confirming that initial treatment of RA with low-dose prednisone plus methotrexate (MTX) results in better clinical and structural outcomes at 1 and 2 years than treatment with MTX alone.
Kommentti: Tutkimuksen «Bijlsma JW. Disease control with glucocorticoid th...»3jatkotutkimus.
In a systemic review «Gorter SL, Bijlsma JW, Cutolo M ym. Current eviden...»2, literature search was performed in Medline, Embase, the Cochrane database, as well as the ACR/EULAR abstracts 2007 and 2008 on a set of questions relating to the use of glococorticoids (GCs) in RA. Eleven publications (including three Cochrane reviews comprising 33 trials) that met the criteria for detailed assessment were found.
GCs are effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or in combination with synthetic DMARD monotherapy or combination therapy. The inhibition of radiographic progression may extend over many years.
In early RA, the addition of low-dose GCs (< 7.5 mg/day) to DMARDs leads to a reduction in radiographic progression; in longstanding RA, GCs (up to 15 mg/day) improve disease activity.
Kommentti: Hyvin tehty katsaus, joka on osaltaan European League Against Rheumatism (Europan reumatologinen yhdistys) nykyisen nivelreuman hoitosuosituksen takana.
In a systematic review «Bijlsma JW. Disease control with glucocorticoid th...»3 of 15 studies involving more than 1400 patients was showed that glucocorticoid treatment for 1–2 years slowed radiographic progression compared with control treatment.
Evidence for longer term disease-modifying benefits of glucocorticoids comes from individual studies with extended follow-up.
In a meta-analysis «Graudal N, Jürgens G. Similar effects of disease-m...»4data from 70 randomized controlled trials (112 comparisons, 16 interventions) investigating the effects of drug treatment on the percentage of the annual radiographic progression rate (PARPR) were summarized in 21 meta-analyses.
Compared with placebo, the PARPR was 0.65 % smaller in the single-DMARD group (P < 0.002) and 0.54 % smaller in the glucocorticoid group (P < 0.00001). Compared with single-DMARD treatment, the PARPR was 0.62 % smaller in the combination-DMARD group (P < 0.001) and 0.61 % smaller in the biologic agent plus methotrexate (MTX) group (P < 0.00001).
In a 2-year randomised double-blind factorial trial «Choy EH, Smith CM, Farewell V ym. Factorial random...»5 in the UK 467 patients with RA within 2 years of diagnosis treated with methotrexate were randomized to added 1) ciclosporin, 2) 9 months intensive prednisolone or 3) both (triple therapy). Over 2 years 132 (28 %) changed therapy and 88 (19 %) were lost to follow-up. The primary outcome was the number of patients with new erosions.
The number of patients with new erosions was reduced by nearly half by adding ciclosporin or prednisolone (p = 0.01 and 0.03); A further reduction in erosive damage was seen with combined use of both treatments. Their effects on erosive damage appeared independent. Triple therapy reduced disability and improved quality of life compared with methotrexate; ciclosporin and prednisolone acted synergistically. More patients withdrew because of adverse events with triple therapy, without an increase in serious adverse effects.
In a randomized controlled trial «Hafström I, Albertsson K, Boonen A ym. Remission a...»6in Sweden 211 patients with RA had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs. A total of 150 could be included in analysis. Radiographs of hands and feet were scored using the Sharp-van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was < 2.6.
At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30 %, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years.
In a German study 192 patients with active early RA (disease duration less than two years.) received either prednisolone 5 mg/day or placebo on concomitant DMARD therapy with parenteral gold or methotrexate for two years «Wassenberg S, Rau R, Zeidler H ym. A dose of only ...»7. 166 were available for intention to treat analysis (ITT), and 76 completed the study per protocol.
Radiographs of hands and feet were taken at baseline, and at 6, 12 and 24 months. Structural damage was assessed using change in the Ratingen score (0–190 scale) as the primary outcome, and change in the Sharp/van der Heijde score (0–448 scale). Progression of the Ratingen score was significantly less at all consecutive time points in the prednisolone group compared to the control group, with the greatest difference after 6 months. At 24 months the increase in score in the prednisolone group was 1.2 + 3.5, (95 % CI 0.4–2.1) and in the placebo group 4.3 + 6.8 (95 % CI 2.7–5.9) (p = 0.006, ITT-analysis). This was confirmed by the results of the Sharp/van der Heijde erosion and total score with an increase of the total score of 5.3 + 10.7 units in the prednisolone compared to 11.4 + 19.1 in the placebo group (p = 0.022) at 24 months.
Systeemisiä kortikoideja suositellaan käytettäväksi nivelreuman hoidossa huomioiden mahdolliset vasta-aiheet.
Suositus on vahva, koska systeeminen kortikoidihoito helpottaa nopeasti oireita, estää nivelten vaurioitumista ja on halpaa.