Effekte einer Tocilizumab-Therapie auf die Knochendichte, Marker des Knochenstoffwechsels und Aktivitätsparameter bei TNF-α vortherapierter aktiver rheumatoider Arthritis

 

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Zusammenfassung

Ziel der 1-jährigen Prospektivstudie war die Analyse einer Therapie mit Tocilizumab (TOZ), einem anti-IL-6-Rezeptor-Antikörper, auf die Knochendichte, Marker des Knochenstoffwechsels und Aktivitäts-/Funktionsparameter bei TNF-α vortherapierter aktiver rheumatoider Arthritis. Hierzu wurden 37 Patienten eingeschlossen, 15 davon beendeten die Studie vorzeitig (9 × aufgrund von Nebenwirkungen/anhaltenden Infektionen, 1 × bei Schwangerschaftseintritt, 3 × wegen massiver allergischer Reaktionen und 2 × aufgrund von Wohnortwechsel). Somit gingen in die Endauswertung 22 Patienten mit aktiver rheumatoider Arthritis ein (16 Frauen, 6 Männer, Durchschnittsalter 62 Jahre, durchschnittliche Krankheitsdauer 11 Jahre). 19 Patienten/Innen erhielten eine Kombinationstherapie von TOZ (8 mg/kg KG alle 4 Wochen) in Kombina­tion mit Methotrexat (durchschnittlich 15 mg/Woche) und 3 Patienten/Innen eine TOZ-Monotherapie aufgrund von MTX-Unverträglichkeit. Alle Pa­tienten hatten zu Studienbeginn≥10 mg Prednisolonäquivalent täglich. Folgende Outcomeparameter wurden zu Beginn und 1 Jahr nach Beginn der TOZ-Therapie erhoben: Knochendichte mittels dualer Photonenabsorptionsmetrie (DXA; am gesamten rechten Schenkelhals und der LWS), Marker des Knochenstoffwechsels (Osteocalcin, N-Terminales Telopeptid des Typ I Kollagens – NTx), C-reaktives Protein und Blutsenkung, Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ) und Funk­tionsfragebogen Hannover (FFbH). Es zeigte sich bei der axialen Knochendichte eine tendenzielle, nicht signifikante Zunahme, bei konstanten Werten am gesamten rechten Schenkelhals. Bei den Markern war ein signifikanter Anstieg beim Osteocalcin objektivierbar (P<0,021), und eine tendenzielle, nicht signifikante Abnahme beim NTx als Abbaumarker (P<0,054). Die Akut-Phase-Reaktanten (BSG, CRP) zeigten erwartungsgemäß einen Abfall, passend hierzu die signifikante Verbesserung im DAS28 (P<0,0001), bei gleichbleibenden Werten im HAQ und FFbH. Die 1-jährige TOZ-Therapie, z.T. in Kombination mit MTX, resultierte bei aktiver – mit anti-TNF-α vortherapierter – rheumatoider Arthritis in osteoprotektiven Effekten sowie einer signifikanten Abnahme der Krankheitsaktivität.

Abstract

The aim of this study was to analyse the effects of a tocilizumab (TOZ) therapy, an anti-IL-6 receptor antibody, on bone mineral density, markers of bone metabolism, parameters of disease activity and function in active rheumatoid arthritis (RA) with inadequate response to tumour necrosis factor inhibition. 37 patients were included in the study, 15 of them terminated the study prematurely because of side effects/persistent infections (9), pregnancy (1), allergic reaction (3), change of residence (2). Finally, 22 patients with active RA could be evaluated (16 females and 6 males, average age 62 years, average disease duration 11 years). 19 patients received a combination medication with TOZ (8 mg/kg BW every 4 weeks) and methotrexate (average dose 15 mg/week) and 3 patients a monotherapy with TOZ because of MTX intolerance. All patients were on prednisolone≥10 mg/day prior to initiation of the trial. The following outcome parameters were determined at baseline and after 1 year under TOZ therapy: bone mineral density (DXA; right total hip and lumbar spine), markers of bone metabolism (osteocalcin, N-terminal telopeptide of type I collagen – NTx), C-reactive protein und erythrocyte sedimentation rate (ESR), Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ), and function questionnaire Hannover (FFbH). The bone mineral density of the lumbar spine showed a tendency to increase, whereas the total hip showed constant values. The bone markers showed a significant increase of osteocalcin (P<0.021), and a tendency of decreased NTx as a resorption marker (P<0.054). The acute phase reactants (ESR, CRP) showed the expected decline. Furthermore, there was a significant improvement of the DAS28 (P<0.0001), whereas HAQ and FFbH remained constant. The 1-year TOZ therapy, in mono- as well as in combination therapy with MTX, resulted in osteoprotective effects and a decrease in disease activity in patients with RA and an inadequate response to TNF-α inhibition.

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