Combination biologics or targeted synthetic disease-modifying anti-rheumatic drugs in the treatment of spondyloarthritis: a systematic literature review

ABSTRACT

Introduction

The advent of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have transformed the management of immune-mediated rheumatic diseases, including spondylarthritis (SpA). However, the data about combining b/ts DMARDs in the treatment of SpA are scarce. The study objectives were to assess the efficacy and safety of combination b/tsDMARD in SpA.

Methods

We conducted systematic literature review (PubMed and Medline) with two independent reviewers, one adjudicator, exploring the efficacy and safety of combination b/tsDMARDs in the treatment of SpA. Inclusion criteria were studies published in last 20 years, English language, interventions included use of two b/tsDMARDs, and minimal three-month follow-up.

Results

Out of 1936 initial hits, 28 manuscripts fulfilled the inclusion criteria. Two were randomized controlled trials, and the remaining were retrospective cohort studies or case series. Combination of apremilast with bDMARD, or TNF inhibitor plus IL12/23 inhibitor were the commonest and reported good efficacy with no increased safety signal.

Conclusions

There is not enough data to fully evaluate efficacy and safety of combination b/tsDMARDs in SpA treatment. Limited information shows apremilast plus bDMARD, or TNF inhibitor plus IL12/23 inhibitor combination to be efficacious and safe. Randomized controlled trials and larger cohort with a longer follow-up are required.

KEYWORDS:

• Spondyloarthritis
• combination biologics
• targeted synthetic DMARDs
• TNF inhibitors
• IL-17 inhibitors
• JAK inhibitors
• PDE4 inhibitor
• IL-23 inhibitors

Article highlights

• This pioneering systematic literature review assesses the efficacy and safety of combining biologic DMARDs (bDMARDs) or pairing a bDMARD with a targeted synthetic DMARD (tsDMARD) in the treatment of Spondyloarthritis (SpA).

• This review includes various randomized controlled trials, retrospective cohort studies, and case series.

• It underscores the need for randomized controlled trials or larger cohort studies with extended follow-up periods.

• More data is needed to gain comprehensive insights into the effectiveness and safety of combination biologics for patients with ‘difficult-to-treat’ spondyloarthritis.

• Promisingly, in cases where standard single biologic or tsDMARD treatments have failed, combination therapy demonstrates efficacy, as indicated by case reports and small case series, without compromising safety.

Declaration of Interest

A Deodhar declares the following conflicts of interest: Consulting, Advisory Boards: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, UCB, and Research Grants: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.