Comparison of tocilizumab and tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective analysis of 1603 patients managed in routine clinical practice
Marina Backhaus
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Jrg Kaufmann
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Constanze Richter
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Siegfried Wassenberg
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Anne-Eve Roske
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Peter Hellmann
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Markus Gaubitz
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C. Richter Internistisch-rheumatologische Schwerpunktpraxis
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Stuttgart
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Germany
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J. Kaufmann Praxis Dr. med Jorg Kaufmann
,
Ludwigsfelde
,
Germany
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) Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie
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Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin
,
Germany
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M. Gaubitz Akademie fur Manuelle Therapie an der WWU Munster, Interdisziplinare Diagnostik und Therapie
,
Munster
,
Germany
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P. Hellmann Chugai Pharma
,
Frankfurt
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Germany
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A.<E. Roske Roche Pharma AG
,
Grenzach-Wyhlen
,
Germany
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S. Wassenberg Fachkrankenhaus Ratingen - Rheumatologische Klinik, Rheumazentrum Ratingen
,
Ratingen
,
Germany
Tocilizumab (TCZ) and tumour necrosis factor inhibitors (TNFi) are recommended for the treatment of rheumatoid arthritis (RA) in patients with inadequate response (IR) to prior disease-modifying antirheumatic drugs (DMARDs). This retrospective analysis assessed the efficacy of TCZ and TNFi, alone or in combination with DMARDs, in 1603
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patients with IR to previous treatment with either DMARDs
(DMARD-IR) and/or TNFi (TNFi-IR), initiating treatment
with TCZ or a TNFi, managed in routine clinical practice.
Patients were grouped according to treatment history and
treatment initiated: DMARD-IR patients initiating treatment
with TCZ + DMARD (DMARD-IR TCZ) or TNFi + DMARD
(DMARD-IR TNFi), DMARD-IR and/or TNFi-IR patients
initiating treatment with TCZ monotherapy (TCZ mono) or
TNFi monotherapy (TNFi mono), and TNFi-IR patients
initiating treatment with TCZ + DMARD (TNFi-IR TCZ) or TNFi
+ DMARD (TNFi-IR TNFi). Patients initiating treatment with
TCZ generally had more severe disease and longer disease
duration compared with the corresponding TNFi group.
Significantly more patients achieved remission (DAS28 ESR
<2.6) in the TCZ groups compared with corresponding TNFi
groups (DMARD-IR, TCZ 44.0 % vs. TNFi 29.6 %;
monotherapy, TCZ 37.2 % vs. TNFi 30.2 %; TNF-IR, TCZ 41.3 %
vs. TNFi 19.2 %; p<0.001 for all comparisons). More patients
achieved moderategood responses (EULAR criteria) in the
TCZ treatment groups (7985 %) compared with TNFi
treatment groups (6581 %). Patient-reported outcomes showed
greater improvements in TCZ compared with TNFi groups.
In patients with inadequate response to DMARDs and/or
TNFi treated in routine clinical practice, TCZ in combination
with DMARDs or as monotherapy resulted in significantly
more patients achieving remission and more marked
improvements in patient-reported outcomes compared with TNF
inhibitors.
Rheumatoid arthritis (RA) is a common chronic
inflammatory disease associated with progressive joint
destruction, pain, fatigue and disability. Current treatments target
the inflammatory response using disease-modifying
antirheumatic drugs (DMARDs) and biological agents, in
combination or as monotherapy. Five classes of biologics
with differing modes of action are currently used in the
treatment of RA: tumour necrosis factor inhibitors (TNFi)
(adalimumab, certolizumab, etanercept, golimumab and
infliximab), an interleukin (IL)-1 receptor antagonist
(anakinra), a selective T-cell costimulatory modulator
(abatacept), a chimeric anti-CD20 monoclonal antibody
(rituximab) and a humanised antiIL-6 receptor antibody
(tocilizumab (TCZ)). Treatment guidelines recommend
DMARDs (initially methotrexate [MTX]) as immediate
first-line therapy in patients with RA, followed by
combination therapy with conventional DMARDs, or with
biological agents in combination with DMARDs, should
patients fail to achieve remission or low disease activity
on DMARDs alone [1, 2]. Monotherapy with biologics is
not generally recommended for all agents in current
guidelines, although in German guidelines, TCZ is
recommended as monotherapy particularly in patients with
intolerance to MTX or when the continuation of MTX
therapy is considered inappropriate for other reasons [3]. The
majority of available data on biologics in RA have been
from studies of TNFis, and although shown to be more
effective in combination with MTX than MTX alone,
TNFi monotherapy was also shown to be less effective
than combination therapy [48]. In more recent studies,
TCZ has been shown to be effective both in combination
with DMARDs and also as monotherapy in patients who
had previously had an inadequate response to DMARDs
(DMARD-IR) [913] or to TNF inhibitors (TNFi-IR)
[1416]. Most recently, the large Phase IV ADACTA trial
demonstrated superior efficacy for monotherapy with TCZ
as compared to monotherapy with the TNFi adalimumab
in patients who were intolerant to, or unsuitable for,
treatment with methotrexate [17]. However, such suitably
powered randomised clinical head-to-head trials for
biologics in RA are rare. Due to strict inclusion and
exclusion criteria, a randomised trial might not reflect cl (...truncated)