J Rheum Dis.  2024 Apr;31(2):86-96. 10.4078/jrd.2023.0045.

Real-world effectiveness of a single conventional diseasemodifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study

• So MW
• Kim SH
• Kim DW
• Sung YK
• Choe JY
• Lee SI
• Hur JW
• Lee HS
• Lee SH
• Kim JR

• KMID: 2554324
• DOI: http://doi.org/10.4078/jrd.2023.0045

Abstract

Objective
The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea.
Methods
At the treating physicians’ discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months.
Results
Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs −0.18, −0.38, and −0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus antiTNF therapy than with multiple cDMARDs (BGD −0.18, −0.19, and −0.19 points, respectively; all p≤0.024).
Conclusion
In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Keyword

Rheumatoid arthritis; Disease-modifying anti-rheumatic drugs; Tumor necrosis factor inhibitors

Figure

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  Figure 1 Patient disposition. Anti-TNF: anti-tumor necrosis factor agent, cDMARD: conventional disease-modifying anti-rheumatic drug, FAS: full analysis set, PPS: per-protocol set.

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  Figure 2 Change from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR) scores at 3, 6, and 12 months (per-protocol set). Results of ANCOVA of LSMs using patient age, duration of rheumatoid arthritis, and baseline DAS28-ESR score as covariates. Bars indicate 95% confidence intervals for each treatment group. Values above bars indicate the difference between the cDMARD+anti-TNF and cDMARDs groups. Baseline mean DAS28-ESR scores were 5.62 points in the points in the cDMARD+anti-TNF group vs 4.77 points in the multiple cDMARD group (p<0.001). ANCOVA: analysis of covariance, anti-TNF: anti-tumor necrosis factor agent, cDMARD: conventional disease-modifying anti-rheumatic drug, LSM: least square.

• 

  Figure 3 Effect of treatment on baseline disease activity status (per-protocol set). Proportion of patients with low, moderate or high disease activity at months 3, 6, and 12 in patients with (A) moderate disease activity at baseline, and (B) high disease activity at baseline. Based on European League Against Rheumatism (EULAR) response criteria, disease activity was classified as low (DAS28-ESR ≤3.2), moderate (DAS28-ESR >3.2 to ≤5.1) or high (DAS28-ESR >5.1) at baseline, then reclassified at each timepoint. There were no significant between-group differences in disease activity status at any timepoint. Anti-TNF: anti-tumor necrosis factor agent, cDMARD: conventional disease-modifying anti-rheumatic drug, DAS28-ESR: disease activity score 28-joint count with erythrocyte sedimentation rate.

• 

  Figure 4 Change from baseline in quality-of-life, as measured by KHAQ-20 scores, at 3, 6, and 12 months (per-protocol set). Results of ANCOVA of LSMs means using patient age, duration of rheumatoid arthritis, and baseline KHAQ-20 scores as covariates. Bars indicate 95% confidence intervals for each treatment group. Values above bars indicate the difference between the cDMARD+anti-TNF and cDMARDs groups. Baseline mean KHAQ-20 scores were 0.95 points in the cDMARD+anti-TNF group vs 0.59 points in multiple cDMARD group (p=0.013). ANCOVA: analysis of covariance, anti-TNF: anti-tumor necrosis factor agent, cDMARD: conventional disease-modifying anti-rheumatic drug, KHAQ: Korean Health Assessment Questionnaire, LSM: least square mean.

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