Initial Combination Strategy for Arthritis Could Increase Risk of Low Persistence, Adverse Events

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A study of more than 2500 patients with chronic inflammatory arthritis suggests an initial targeted therapy strategy using combination therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) and conventional synthetic DMARDs could place patients at greater risk of decreased treatment persistence and increased risk for adverse events.

A nested cohort study of patients within the BIOBADASER III registry, results of the study, which compared the effects of monotherapy and combination therapy as initial treatment strategies in rheumatoid arthritis [RA], psoriatic arthritis [PsA], and ankylosing spondylitis [AS], suggest an initial strategy of combination therapy was associated with decreased treatment persistence and increased risk of adverse events relative to an initial treatment strategy favoring monotherapy.¹

“Analysis of a large database collected under real- world conditions shows that initiation of targeted therapy in monotherapy has a significantly better persistence and safety profile than in combination with csDMARD in patients with PsA and AS,” wrote investigators.¹ “In patients with RA, the results also suggest that monotherapy should be considered as a therapeutic option with a higher chance of persistence.”

According to the 2019 guidelines from the European Alliance of Associations for Rheumatology, when a bDMARD is indicated, it should be used in combination with a csDMARD due to the improved efficacy and reduced immunogenicity of the combination.² However, as investigators note, more recent data has questioned whether this is the most efficacious strategy for management of chronic inflammatory arthritis.¹

In the current study, a team led by Federico Díaz-González, MBBS, and a team of colleagues from institutions in Spain launched the current study to better understand the potential risk of decreased treatment persistence and increased risk of adverse events associated with each initial treatment strategy. To do so, investigators designed their study as an analysis of data from the BIOBADASER III registry. The primary outcome of interest was the persistence of the treatment initial strategy, which investigators defined as the time elapsed from date of initiation until discontinuation of the initial strategy.¹

Overall, the BIOBADASER III registry included 4051 patients. Of these, 2589 met selection criteria for the current study. Among this cohort, 1192 patients had RA, 697 had PsA, and 632 has AS. The median duration of the initial treatment strategy was 20 (12-32) months for patients with RA, 22 (12-40) months for patients with PsA, and 24 (14-43) months for patients with AS.¹

In the RA group, 245 had monotherapy as an initial treatment strategy and 947 had combination strategy as their initial treatment strategy. In the PsA group, 248 had monotherapy as an initial treatment strategy and 449 had combination therapy as their initial treatment strategy. In the AS group, 485 had monotherapy as an initial treatment strategy and 147 had combination therapy as their initial treatment strategy.¹

Upon analysis, results suggested the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58; 95% confidence interval [CI], 1.00-2.50; P = .049), PsA (HR, 2.48; 95% CI, 1.65-3.72) and AS (HR 16.77; 95% CI 7.37– 38.16; P < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use, or type of b/tsDMARD. Investigators also pointed out an initial combination strategy was associated with an increased incidence of adverse events in pooled analyses of the patient cohort (Incidence rate ratio, 1.13; 95% CI, 1.05-1.21).¹

“The main objective of this work was to analyse patient and disease characteristics associated with persistence on initial targeted therapy strategy, either as monotherapy or in combination with csDMARD, in RA, PsA and AS patients using a national registry database under real-world conditions,” investigators wrote.¹ “The pattern of b/tsDMARD use in routine clinical practice shown in our study is somewhat consistent with clinical practice guideline recommendations.”

References:

1. Exposito L, Sánchez-Piedra C, Vela-Casasempere P, et al. Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis [published online ahead of print, 2023 Sep 16]. Eur J Clin Invest. 2023;e14095. doi:10.1111/eci.14095
2. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. doi:10.1136/annrheumdis-2019-216655