Patient Characteristics Influence Choice of Biologic Disease-Modifying Antirheumatic Drugs

Patient characteristics appear to influence the choice of biologic disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA), as significant channeling of older and less healthy individuals to non-tumor necrosis factor inhibitor (non-TNFi) bDMARDs was demonstrated in a large register-based study published in the Annals of the Rheumatic Diseases.¹

Although there has been rapid availability of a wide range of bDMARDs for the treatment of RA, TNFi drugs remain the most common choice as first bDMARD. Often, perceived or established differences between bDMARDs may lead to a nonrandom allocation of treatment, and such channeling may bias direct comparisons of treatment outcomes.^2,3 

Therefore, researchers in Sweden evaluated the baseline characteristics of 6481 patients with RA starting a TNFi, rituximab, abatacept, or tocilizumab as their first bDMARD, and 2829 patients after a switch from a TNFi as their first bDMARD from 2011 to 2015.¹ The researchers found that patients initiating non-TNFis were older than those starting TNFis and had lower socioeconomic status, higher disease activity, and a greater burden of other diseases (eg, malignancy, serious infections, and diabetes). 

These differences were found to be most prominent at first bDMARD initiation and were linked to treatment outcome independent of therapy producing worse apparent safety and effectiveness for non-TNFi biologics. However, adjusting for age and sex of the TNFi group reduced these differences considerably.

This study demonstrated that there are substantial differences in baseline characteristics among patients assigned to different bDMARDs and that a direct comparison across therapies would not give accurate estimates of the treatments’ relative effect but would be biased toward TNFis.¹ The authors concluded that, “Unless differences in age, medical history, and RA disease activity are taken into account in studies of the relative safety and effectiveness of bDMARDs, most results will be severely confounded.”

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References

1. Frisell T, Baecklund E, Bengtsson K, Di Giuseppe D, Forsblad-d’Elia H, Askling J, on behalf of the ARTIS Study group. Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics [published online December 13, 2017]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-212395
2. Wolfe F, Flowers N, Burke TA, et al. Increase in lifetime adverse drug reactions, service utilization, and disease severity among patients who will start COX-2 specific inhibitors: quantitative assessment of channeling bias and confounding by indication in 6689 patients with rheumatoid arthritis and osteoarthritis. J Rheumatol. 2002;29:1015-1022.
3. Petri H, Urquhart J. Channeling bias in the interpretation of drug effects. Stat Med. 1991;10:577-581.