TNFi Combination Therapy vs Monotherapy Improves Drug Survival in Psoriatic Arthritis

Researchers compared the effectiveness of tumor necrosis factor inhibitor combination therapy vs monotherapy in psoriatic arthritis.

Compared with tumor necrosis factor inhibitor (TNFi) monotherapy, combination therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) may not improve disease activity, but may improve drug survival, in psoriatic arthritis (PsA), according to study results published in The Journal of Rheumatology.

Researchers assessed the differences in effectiveness and treatment outcomes for patients with PsA receiving TNFi monotherapy or combination therapy with csDMARDs. Using 5 biologic cohorts investigated between 2000 and 2015, the researchers analyzed data from patients across the ATTRA registry in the Czech Republic, the Swiss Clinical Quality Management PsA registry, the Hellenic Registry of Biologics Therapies in Greece, the University of Bari, Italy, PsA biologics database, and the Bath, United Kingdom, PsA cohort. Researchers performed separate analyses on the combined Italian/Swiss cohorts for change in rate of disease progression, as measured by the well-validated 28-item Disease Activity Score (DAS28), and the combined Italian, Swiss, and Bath cohorts for rate of change in physical function, measured using the Health Assessment Questionnaire (HAQ). The study analyzed persistence on TNFi monotherapy or combination therapy with TNFi and csDMARDS using the Kaplan-Meier method, and equality of survival using logrank tests.

The final cohort included 2293 patients with PsA. Analysis of the Swiss (P =.002), Greek (P =.021), and Bath (P =.014) cohorts revealed that compared with patients who received only TNFis, those who received TNFis in combination with the most widely used csDMARD, methotrexate, had longer drug survival. However, in the Italian cohort, the monotherapy group persisted longer (P =.030) than the combination therapy group. In the combined Italian/Swiss dataset (n=1066), there was no significant differences in rates of change of DAS28 between the 2 groups. Similarly, among the Italian/Swiss and Bath cohorts (n=1205) combined, there were no significiant differences in rates of change in the HAQ with monotherapy or combination therapy.

Researchers noted that sex was a major risk factor for TNFi survival, with men persisting for longer; patients mostly discontinued TNFi monotherapy due to adverse effects and lack of treatment efficacy. Findings from the study also showed that a lower percentage of patients receiving both TNFi and methotrexate discontinued combination therapy potentially because of inhibition of the development of antidrug antibodies from the combination of drugs. However, the researchers concluded that the reason for this finding was not clear and further investigation needs to be conducted.

Study limitations included the fact that HAQ was the only outcome measure commonly recorded across all cohort registries, and that patients enrolled in the registries across Europe had differing baseline disease activity and severity scores; however, the researchers created comparable clinical outcome measures by analyzing the rates of change rather than absolute change in DAS28 or HAQ from baseline. In addition, effectiveness assessment of TNFi treatment applied only to physical function and not to the other assessments, as a result of which efficacy of TNFi-only vs combination therapy with TNFi and csDMARDs did not include factors that might affect quality of life in PsA.

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Researchers concluded, “[W]e have demonstrated the feasibility of combining biologics registry and database data to investigate the comparative effectiveness of TNFi treatment for PsA but as with all observational studies the results need to be interpreted with caution.”


Thomas ML, Shaddick G, Charlton R, et al. Tumor necrosis factor inhibitor monotherapy versus combination therapy for the treatment of psoriatic arthritis: combined analysis of European biologics databases [published April 1, 2020]. J Rheum. doi:10.3899/jrheum.190815