Drivers of First- and Second-Line Treatment in Rheumatoid Arthritis Identified

Using real-life data, investigators were able to identify factors that influence clinicians’ choice of first- and second-line biologic therapy in rheumatoid arthritis (RA).

A study published in Clinical Rheumatology used a large cohort of real-life RA patients enrolled in the Italian Lombardy Rheumatology Network (LORHEN) Registry.

The goal was to retrospectively analyze the factors influencing the choice of first-line biologic disease modifying anti-rheumatic drugs (bDMARDs) or the switching strategy, with a primary focus on abatacept (Orencia) or tocilizumab (Actemra) compared with tumor necrosis factor (TNF) inhibitors (TNFi).

In the study, investigators analyzed individuals enrolled in the LORHEN Registry, including patients treated with bDMARDs in 8 rheumatologic centers in Northern Italy. The analysis was limited to patients enrolled after January 1, 2010.

A total of 1910 patients were included in the study, and divided into first-line and second-line bDMARD.

Comorbidities were categorized into the following organ systems groups: arterial hypertension, cardiovascular disease, diabetes, dyslipidemia, osteoporosis, peripheral neuropathy, pulmonary disease, thyroid autoimmune disease, and other unrelated comorbidities.

There were 1264 patients in the first-line bDMARD treatment group, of whom 115 received abatacept first-line, 130 received tocilizumab first-line, and 1019 received TNFi first-line.

Second-line bDMARD treatment included a total of 646 patients, of whom 143 received abatacept, 97 received tocilizumab, and 406 received TNFi.

At the time of first bDMARD initiation, mean age was statistically different for abatacept versus TNFi (58.74 ± 13.39 versus 53.42 ± 13.66; P = 0.0003) and for tocilizumab versus TNFi (57.84 ± 10.89 versus 53.42 ± 13.66; P = 0.002).

The results of the study showed that abatacept was associated with a higher prevalence of positive LTBI status (29.63%) compared with tocilizumab (16.26%) and TNFi (15.64%). Treatment preceding the initiation of first-line bDMARD showed tocilizumab was significantly more prescribed as a monotherapy compared with abatacept (P = 0.02) and TNFi (P = 0.01).

Regarding comorbidity prevalence, the findings showed dyslipidemia occurred in 14.78% of patients treated with abatacept compared with 10% of patients treated with tocilizumab, and 7.16% who started TNFi. Furthermore, arterial hypertension was more present in the abatacept group compared with the TNFi group.

Pulmonary comorbidities were statistically more represented in the abatacept group compared with the TNFi group, and did not reach statistical significance for the tocilizumab group.

Comorbidity prevalence categorized as “other” in the LORHEN Registry affected 67.83% of patients in the abatacept group, 47.69% in the tocilizumab group, and 41.51% in the TNFi group.

Pulmonary extra-articular involvement of disease was found in 4 patients in the abatacept-treated group, 4 in the tocilizumab group, and 18 in the TNFi group. Rheumatoid vasculitis was found in only 1 patient in the TNFi group. Rheumatoid nodules occurred in 6 patients treated with first-line abatacept, 1 in the tocilizumab group, and 25 in the TNFi group. Ocular involvement was reported in 6 patients treated with TNFi and none in the 2 other groups.

The results of the study also found that having 2 or more comorbidities was significantly associated with the prescription of abatacept versus both tocilizumab and TNFis.

Adverse events (AEs) in first-line bDMARD were found to influence the choice of second-line treatment in favor of abatacept compared with TNFi. However, neither the choice of abatacept nor tocilizumab as second-line drugs was influenced by the discontinuation of the prior bDMARD due to primary or secondary inefficacy, according to the study.

Age was significantly higher in the abatacept second-line group compared with the TNFi group, although it was not higher compared with tocilizumab. No significant difference in age was found between the tocilizumab group and the TNFi group.

Disease activity at the time of switch was significantly higher when investigators compared abatacept versus TNFi, and tocilizumab versus TNFi. The difference in DAS28 between abatacept and tocilizumab was not significant, according to the study.

MTX combination therapy with a second-line bDMARD were prescribed in 54.64% of patients in the tocilizumab arm compared with 67.98% in the TNFi arm, and 64.34% of patients on abatacept. No significant difference of concomitant MTX rates were observed between abatacept and TNFi.

Second-line therapy with abatacept was primarily selected according to age, suspension of first-line bDMARD due to AE, extra-articular nodulosis, and neuropathy. However, high DAS28 disease activity, positive LTB screening, pulmonary or cardiovascular comorbidities, and neuropathy were all factors influencing the choice of second-line tocilizumab compared with TNFI.

Limitations in the analysis were its retrospective nature, which may be prone to assignment for treatment and patient selection bias; detailed information may be missing and comorbidity classification may not have been fully useful for the study purposes; the relatively high percentage of missing data on anti-citrullinated protein antibodies and/or rheumatoid factor positivity prevented the investigators from accurately analyzing their potential role in the biologic drug choice; rituximab was not included in the study due to the relatively smaller size of the treatment population, the well-known and unusual potential drivers of choice associated with the drug, and the different frequency of administration and maintenance compared with other bDMARDs.

Lastly, the registry design prevented investigators from evaluating the influence of costs or the patient’s preferences for a specific route of administration in guiding therapeutic decisions.

The results of the study indicated that age, infection risk, number and type of comorbidities, and preference for monotherapy are the main factors that influence the choice of abatacept or tocilizumab compared with TNFi. Furthermore, interruption of previous bDMARDs due to AEs influenced choice towards abatacept, while failing a first-line TNFi encouraged the switch to agents with a different mechanism of action.