Risiko for infeksjoner
TNF-antagonister påvirker immunsystemet og bruken av slike legemidler kan påvirke kroppens forsvar mot infeksjon og malignitet. Alle pasienter som vurderes for biologisk behandling skal undersøkes for latent tuberkulose og andre pågående infeksjoner før oppstart av biologisk behandling. Alvorlige infeksjoner rammer færre enn 1 av 100 pasienter som behandles med Enbrel.1
For å forebygge infeksjoner som følge av immunsuppressiv behandling anbefales både screening av latente infeksjoner (som tuberkulose, hepatitt B-virus) før oppstart av biologisk behandling og vaksinasjon før og under behandling med TNF-hemmere.1
Enbrel - risiko for tuberkulose
Britiske2 og franske3,4 registerdata innen RA tar for seg forekomsten av tuberkulose som bivirkning av anti-TNF terapi:
BSRBR registry
Methods: Data from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 etanercept, 3295 infliximab, 3504 adalimumab) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs.
Results: The rate of TB was higher for the monoclonal antibodies adalimumab (144 events/100 000 personyears) and infliximab (136/100 000 person-years) than for etanercept (39/100 000 person-years). After adjustment, the incidence rate ratio compared with etanercept-treated patients was 3.1 (95% CI 1.0 to 9.5) for infliximab and 4.2 (1.4 to 12.4) for adalimumab.
Conclusion: “The rate of tuberculosis in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving infliximab and adalimumab than in those receiving etanercept2”
RATIO registry
Objective: To describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence.
Methods: We conducted an incidence study and a case–control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents.
Results: The sex- and ageadjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7–15.5)and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4–25.8] and SIR 29.3 [95% CI 20.3–42.4]versus SIR 1.8 [95% CI 0.7–4.3], respectively). In the case–control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6–69.0]and OR 17.1 [95% CI 3.6–80.6], respectively).
Conclusion: The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.3
Reaktivering av latent tuberkulose ved anti TNF-behandling?
TNF-α er en sentral komponent i forsvaret mot intracellulære mikrober. Mykobakterielle granulomer begrenser både inflammasjon og disseminering av mykobakteriene.
Monoklonale antistoff binder seg raskt og irreversibelt til membranbundet TNF-α og leder til apoptose. TNF-reseptor-IgG-fusjonsprotein (Enbrel) har ikke denne egenskapen.
Uttalt apoptose av granulomceller vil føre til disintegrering av tuberkulomet og reaktivering av latent tuberkulose. Inntil videre har man likevel valgt å anse at den økte infeksjonsrisikoen er lik for alle TNF-α-hemmerne.5
1. Enbrel preparatomtale (SPC), kap. 4.4, 2. Dixon WG, Hyrich KL, Watson KD et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 2010;69:522–528, 3. Tubach F, Salmon D, Ravaud P et al. Risk of Tuberculosis Is Higher With Anti–Tumor Necrosis Factor Monoclonal Antibody Therapy Than With Soluble Tumor Necrosis Factor Receptor Therapy. Arthritis & Rheumatism 2009 July;60(7):1884–1894, 4. Salmon-Ceron D, Tubach F, Lortholary O et al. Drug-specifi c risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry. Ann Rheum Dis 2011;70:616–623, 5. Harboe E, Damås JK, Omdal R et al. Infeksjonsrisiko ved bruk av selektivt immunmodulerende midler mot revmatoid artritt 1867. Tidsskr Nor Legeforen nr. 16, 2012;132:1867 – 71
