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Drug survival of second biological disease-modifying anti-rheumatic drug therapy in patients with rheumatoid arthritis: a retrospective non-interventional cohort analysis

Clinical Research 7 min 6

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Created On: 15/02/2020

Drug survival of second biological disease-modifying anti-rheumatic drug therapy in patients with rheumatoid arthritis: a retrospective non-interventional cohort analysis

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Key take away

Only 56.8% of rheumatoid arthritis (RA) patients continued second biological disease-modifying anti-rheumatic drug (bDMARD) treatment after 12 months (60% if re-start was included). Non-anti-TNF patients had a higher probability of continuing second bDMARD therapy.

Background

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease that causes severe progressive joint damage, functional disability, thereby affecting the overall health-related quality of life. The current treatment guidelines recommend the use of methotrexate (MTX), a synthetic disease-modifying anti-rheumatic drug (sDMARD), in combination with glucocorticoids in newly diagnosed RA patients. If MTX therapy fails to reach the treatment goal, it is recommended to switch to another sDMARD (e.g., sulfasalazine, leflunomide, hydroxychloroquine) or to add a biological DMARD (bDMARD) to MTX therapy. The bDMARDs are distinguished into two broad classes (based on the mechanism of action), anti-TNFs (e.g., Infliximab, Etanercept, Adalimumab, Golumumab, Certolizumab) and non-anti TNFs (e.g., Abatacept, Anakinra, Tocilizumab, Rituximab). According to evidences, the first line DMARDs are usually discontinued after a period of 12 months due to loss of efficacy of the drugs over time and their intolerable side effects. This discontinuation leads to treatment failure and various side effects. It is always a matter of debate whether after using an anti-TNF therapy, treatment with a second-line anti-TNF or treatment with a non-anti-TNF biological is a strategy that maximizes drug survival of a second bDMARD therapy. Therefore, this study was conducted to assess drug survival of a second bDMARD therapy in RA patients hypothesizing that there is a difference in drug survival between a second anti-TNF versus non-anti-TNF therapy.

Rationale behind the research:

There was little known about treatment persistence of the second-line bDMARD and association of the mode of action of such a treatment with different persistence rates. Thus, this study was conducted to determine the drug survival of a second bDMARD therapy in RA patients.

Objective:

To evaluate the discontinuation-, re-initiation- or continuation-rates of a second bDMARD therapy as well as switching-rates to a third bDMARD therapy in RA patients.

Method

Study outcome measures:

Baseline characteritiscs: patient’s age, gender, comorbidity index, duration of first anti- TNF.
The other study outcomes: the rates of switch, discontinuation, and continuation of second bDMARD therapy during the 12-month follow-up period and factors associated with second bDMARD drug survival using multivariate Cox regression analysis

Time Points: At baseline and 12-month

Result

Study outcomes

Baseline: There were no significant differences in baseline characteristics between the groups.

The switch, discontinuation, and continuation rates were estimated to be 24.6% (95% CI: 20.8–28.8), 18.8% (95% CI: 15.5–22.7), and 56.8% (95% CI: 52.1–61.3), respectively
Treatment continuation rates were significantly lower in the anti-TNF group (53.5%, 95% CI: 48.2–58.8) than in the non-anti-TNF group (66.7%, 95% CI: 57.3–74.9)
Treatment discontinuation rates was somewhat lower in the anti-TNF group (17.9%, 95% CI: 14.2–22.4) than in the non-anti-TNF group (21.6%, 95% CI: 14.9–30.3)
Patients who received at least one prescription for a painkiller in the 6 preceding months before index date had a lower risk of discontinuing or switching therapy and patients who started a second bDMARD therapy with an anti-TNF had a higher risk of a switch or discontinuation of therapy than patients who started with a non-anti-TNF

Conclusion

The results of this study indicated that substantial number of RA patients discontinued or switched their second bDMARD therapy within 12 months. This was the first study to analyse drug survival of a second bDMARD therapy in RA patients. The study also showed that discontinuation of a bDMARD therapy does not always leads to therapy failure or serious adverse events. The reasons for switching of therapy were not clearly understood in this study, but according to previous studies the discontinuation of current therapies were due to lack of disease remission and side effects.

Limitations

The results of the comparison of drug survival between anti-TNF and non-anti-TNF agents may be biased due to unobserved patient and treatment characteristics
There was limited data used in this therapy with regard to potential factors associated with second bDMARD discontinuation, so there is a need of detailed data about RA disease severity and disease characteristics

Clinical take-away

Patients on non-anti TNF bDMARDs as second bDMARD therapy have a lower probability to discontinue their treatment. Thus, this study allows a better understanding and interpretation of drug survival observed in clinical practice settings.