Should we combine biologics with methotrexate in axial spondyloarthritis?
Introduction
Historically, the benefit of a combination therapy of bDMARDs and methotrexate (MTX) is based on clinical trials and real life experience in patients with rheumatoid arthritis and an inadequate response to MTX, in whom TNF inhibitors and a variety of other bDMARDs were explored initially. Despite the clinical efficacy of bDMARDs and tsDMARDs in monotherapy, the overall benefit of combining these agents with MTX is further supported by the EULAR recommendations for the management of rheumatoid arthritis [[1], [2]]. A synergistic mechanism of action and the prevention of the development of drug-neutralizing antibodies seem to favour the combination treatment strategy [2]. Whether this concept can be transferred to the management of other inflammatory diseases such as axial spondylarthropathy, is still under debate.
Section snippets
CONS
There are several reasons, why biological disease modifying drug (bDMARD) with methotrexate should not be routinely combined with methotrexate.
Firstly, in contrast to rheumatoid arthritis or psoriatic arthritis, there is no evidence that methotrexate has any meaningful effect on axial or peripheral manifestations of spondyloarthritis (SpA). In a Cochrane review, initially performed in 2004 and updated in 2013, only 3 randomized controlled trials with methotrexate in ankylosing spondylitis (AS,
Pros
Patients with spondyloarthropathies manifest notable clinical responses with bDMARDs therapy [[22], [23], [24], [25]]; yet inhibition of radiographic progression in these patients following blockage of TNFα or IL-17 still seems to be a challenging goal to be achieved [26,27]. In contrast to the rapid clinical response to bDMARDs, their inhibitory effects of on axial radiographic progression appears only following several years of continuous therapy [28]. Interestingly, continuous daily
Declaration of Competing Interest
DP: research grants from Abbvie, MSD, Novartis, Pfizer; consultancy/speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB.
HA: research grants from Abbvie, Pfizer, Yansen; consultancy/speaker fees from: Abbvie, BMS, Illy Lilly, MSD, Novartis, Pfizer, Roche, Neopharm, Perigo.
References (41)
- et al.
Increased efficacy of infliximab associated with methotrexate in ankylosing spondylitis
Joint Bone Spine
(2007 May) - et al.
Immunogenicity and autoimmunity during anti-TNF therapy
Autoimmun Rev
(2013 May) - et al.
Paradoxical immune-mediated inflammation in inflammatory bowel disease patients receiving anti-TNF-α agents
Autoimmun Rev
(2014 Jan) - et al.
New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: a systematic analysis
Autoimmun Rev
(2015 Sep) - et al.
An update on biomarkers in axial spondyloarthritis
Autoimmun Rev
(2016 Jun) - et al.
Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial
Lancet
(2004 Feb 28) - et al.
Clinical utility of random anti-tumour necrosis factor drug testing and measurement of anti-drug antibodies on long-term treatment response in rheumatoid arthritis
Lancet
(2015 Feb 26) - et al.
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
Ann Rheum Dis
(2017 Jun) - et al.
Monotherapy with biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis
Rheumatology (Oxford)
(2017) - et al.
Methotrexate for ankylosing spondylitis
Cochrane Database Syst Rev
(2004)
Methotrexate for ankylosing spondylitis
Cochrane Database Syst Rev
Clinical investigation of methotrexate in the treatment of ankylosing spondylitis
Scand J Rheumatol
Is methotrexate effective in ankylosing spondylitis?
Rheumatology (Oxford)
Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial
J Rheumatol
Methotrexate in the treatment of ankylosing spondylitis
Scand J Rheumatol
No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial
Ann Rheum Dis
Efficacy of SLZ and MTX (alone or combination) on the treatment of active sacroiliitis in early AS
Rheumatol Int
Maintenance of infliximab treatment in ankylosing spondylitis: results of a one-year randomized controlled trial comparing systematic versus on-demand treatment
Arthritis Rheum
Short-term efficacy of combination methotrexate and infliximab in patients with ankylosing spondylitis: a clinical and magnetic resonance imaging correlation
Rheumatology (Oxford)
Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study
Ann Rheum Dis
Cited by (1)
Toxicological considerations in the treatment of axial spondylo-arthritis
2020, Expert Opinion on Drug Metabolism and Toxicology