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Sertolitsumabi nivelreuman hoidossa

Näytönastekatsaukset
Laura Pirilä
4.6.2015

Näytön aste: A

Sertolitsumabi on tehokas nivelreuman hoidossa

Cocharane meta-analyysi «Ruiz Garcia V, Jobanputra P, Burls A ym. Certolizu...»1 5 RCT , yhteensä 2 394 tutkittavaa tehon osalta 2 094 turvallisuuden osalta, tutkimusten kesto 12–52 viikkoa, sertolitsumabi annos 50–400mg s.c. , kolmessa tutkimuksessa vertailu lumelääke kombinoituna metotreksaattiin, kahdessa lumelääke Sertolitsimabi pegol 200mg sc. yhdistettynaä tai ilman metotreksaatti lääkityksen, vertailu lumelääkkeeseen yhdistettynä tai ilman metotreksaattiin aikuisilla nivelreumaa sairastavilla, joille oli aktiivi tauti huolimatta DMARD lääkityksestä. Tutkimusten kesto 12–24 viikkoa. Lääkeellä saatiin sekä ACR20 että ACR 70 vaste: ACR20 24 viikon kohdalla: RR 2,57 (95 % CI 2,16–3,05) ja 52 viikon kohdalla: RR 2,06 (95 % CI 1,61–2,62). kaikilla käytetyillä annoksilla ACR70 24 viikon kohdalla: RR 3,93 (95 % CI 2,41–6,41); 24 viikon kohdalla: RR 3,14 (95 % CI 1,86–5,29), kaikilla käytetyillä annoksilla.

Sertolitsimabi käyttäneillä oli enemmän vakavia infektioita kuin kontrolliryhmässä: Sertolitsimabi 200 mg käyttäneiden ryhmässä (OR 3,30, 95 % CI 1,45–7,51) ja sertolitsimabi 400 mg käyttäneiden ryhmässä (OR 3,25, 95 % CI 1,65–6,39)

Kohonutta verenpainetta oli sertolitsimabia käyttäneiden ryhmässä enemmän kuin kontrolliryhmässä. Sertolitsimabi 200 mg, (OR 2,81 , 95 % CI 1,38–5,75); sertolitsimabiv400 mg (OR 3,23, 95 % CI 1,71–6,08)

Mukaan otetut tutkimukset olivat laadukkaita eikä ollut osoitettavissa biasta, vaikka ne olivat lääketehtaan toimeksiannosta tehtyjä.

A systematic literature review «Launois R, Avouac B, Berenbaum F ym. Comparison of...»2was carried out from January 1, 1980, to June 30, 2009, in the following databases: Medline (from 1996), Embase (from 1980), and Cochrane Library (Central Register of Controlled Trials, from 1993). This review was completed by a manual search in the proceedings of the American College of Rheumatology (ACR) and European League Against Rheumatism congresses since 2004.

The studies searched were the controlled, randomized, double-blind trials published in the English language that included adult patients with RA who had an inadequate or no response to DMARD including MTX. In addition, the studies evaluated anticytokine biotherapies indicated for the treatment of RA versus placebo in combination with continuation of inadequate conventional DMARD. Biologics should be used according to their Summary of Product characteristics. Clinical efficacy should have been assessed by the ACR20, ACR50, and ACR70 response rates14. ACR20 criterion, which characterizes a minimal therapeutic response and was the primary efficacy criterion used in the majority of studies, was retained as the major efficacy outcome in the multiple-treatment metaanalysis. ACR50 response, which possesses better clinical significance, and ACR70 response were used as secondary efficacy criteria. Efficacy evaluation had to be available at 24 ± 8 weeks of treatment. According to the defined inclusion criteria, studies were excluded from the analysis if they included patients with RA naive to DMARD or with inadequate or no response to a previous anti-TNF-α, as well as those that did not report ACR20 rates after about 6 months of treatment.

All the selected randomized studies were comparative versus placebo (therefore the common comparator of the multiple-treatment metaanalysis): 14 of them evaluated the efficacy of an anti-TNF-α therapy (infliximab, etanercept, adalimumab, golimumab, CZP) and 5 an anti-interleukin treatment (anakinra, tocilizumab). The metaanalysis thus involves a total of 7158 patients, of whom 3174 received placebo and 3984 received an anticytokine treatment: 698 were treated with infliximab in 4 studies, 160 with etanercept in 2 studies, 657 with adalimumab in 4 studies, 124 with golimumab in 2 studies, 639 with CZP in 2 studies, 250 with anakinra in 1 study, and 1456 with tocilizumab in 4 studies. The evidence network made up of the 19 selected studies enables

Taulukko 1. Relative efficacy of each treatment vs placebo in the mixed-treatment metaanalysis comparison between the 7 treatments tested.
Infliximab 3.31 (2.05–5.03) 3.31 (2.05–5.03) 3.55 (1.77–7.15)
Infliximab Etanercept 8.07 (3.34–16.75) 11.45 (3.45–31.02)
Adalimumab 3.72 (2.35–5.93) 5.66 (3.15–10.01) 6.63 (3.12–12.69)
Golimumab 3.62 (1.62–6.97) 5.72 (2.07–13.69)
Certolizumab pegol 11.82 (5.98–21.71) 10.81 (4.41–24.02) 15.84 (4.64–43.89)
Anakinra 2.40 (0.96–5.03) 2.84 (0.81–7.26)
Tocilizumab 4.13 (2.64–6.19) 5.68 (2.78–9.93) 8.63 (3.70–16.99)
Fixed-effects Model
Infliximab 3.36 (2.65–4.20) 3.51 (2.62–4.63) 3.18 (2.12–4.63)
Etanercept 7.79 (4.07–13.86) 9.76 (4.09–21.19)
Adalimumab 3.12 (2.46–3.89) 4.87 (3.58–6.54) 6.26 (3.89–9.74)
Golimumab 3.61 (2.14–5.76) 4.77 (2.52–8.38)
Certolizumab pegol 10.94 (7.42–15.81) 9.43 (5.60–15.43) 12.83 (5.61–28.08)
Anakinra 2.24 (1.49–3.26) 2.53 (1.39–4.32)
Tocilizumab 4.09 (3.43–4.86) 5.92 (4.47–7.79) 8.48 (5.37–13.06)

All tested treatments were efficient compared to placebo treatment.

Kirjallisuutta

  1. Ruiz Garcia V, Jobanputra P, Burls A ym. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Cochrane Database Syst Rev 2011;:CD007649 «PMID: 21328299»PubMed
  2. Launois R, Avouac B, Berenbaum F ym. Comparison of certolizumab pegol with other anticytokine agents for treatment of rheumatoid arthritis: a multiple-treatment Bayesian metaanalysis. J Rheumatol 2011;38:835-45 «PMID: 21239748»PubMed