Biologic Dose Cuts Feasible in RA Save

Many patients with rheumatoid arthritis (RA) who achieved remission or low disease activity on biologic treatment were able to reduce the dose of their biologic, particularly if they were also on methotrexate, a retrospective study found.

Among 332 RA patients treated at the Brussels UCLouvain clinic from 2000 to 2018, 140 (42.1%) received a reduced dose of their biologic treatment, while 192 (57.9%) continued on full doses. During a mean follow-up of 14.6 years, 125 of those receiving reduced doses were able to maintain the lower dose and only 15 experienced a relapse that necessitated increasing the dose, according to Patrick Durez, MD, of Université Catholique de Louvain in Brussels, Belgium, and colleagues.

In addition, more patients in the reduced-dose group were receiving concurrent methotrexate (86.7% vs 73.8%), which was a "highly significant" difference (P=0.005), they reported online in Arthritis Research & Therapy.

The success of biologic disease-modifying antirheumatic drug (DMARD) medications in controlling the signs and symptoms of RA and other autoimmune inflammatory diseases has led to broad interest in whether these drugs can be stopped or tapered once remission or low disease activity has been established, which could limit the likelihood of adverse events over the long term, and also lower the cost accrued with these expensive agents.

Stopping entirely often has been associated with risks of relapse, but approaches involving lowering the dose or extending the interval between doses have shown more promise.

Accordingly, Durez and colleagues reviewed the records of RA patients who had received treatment with a biologic for at least 1 year at their clinic, comparing the characteristics of those who remained on full doses and those who reduced their doses.

They found that patients in the reduced-dose group were older at the time of the analysis in 2017 (60.7 vs 55.7, P=0.02), and also at the time of diagnosis (43.1 vs 38.7, P=0.04). More patients in the reduced-dose group were positive for rheumatoid factor (83.3% vs 72.9%, P=0.04), and the duration of disease at the time the current biologic was started was lower in the reduced-dose group (9.7 vs 12.1 years, P=0.034).

Scores on the Health Assessment Questionnaire (HAQ) at the time the current biologic was initiated were lower in the reduced-dose group (1.3 vs 1.5, P=0.048), as were scores on patient global assessment (60.1 vs 67.1, P=0.024).

"Our study showed that different baseline RA characteristics were correlated with the success of the biologic DMARD dose decrease, such as the age at diagnosis, presence of rheumatoid factor, disease duration at the introduction of the first biologic DMARD, HAQ score, patient global assessment score, and combination with methotrexate," the researchers wrote.

Patients who continued to receive full doses had been exposed to more different biologics. About 32% of patients in the full-dose group had received two biologics compared with 26.6% of those in the reduced-dose group. "This likely reflects a better primary response to biologic DMARDs in the reduced-dose group than in the stable-dose group," the researchers observed.

The most commonly used biologics in the overall cohort were tumor necrosis factor (TNF) inhibitors (68%). Infliximab (Remicade) was used by 29%, etanercept (Enbrel) by 18%, adalimumab (Humira) by 13%, golimumab (Simponi) by 7%, and certolizumab (Cimzia) by 1%.

Non-TNF biologics included tocilizumab (Actemra) in 15%, rituximab (Rituxan) in 10%, and abatacept (Orencia) in 7%.

Almost 67% of patients on adalimumab were able to reduce the dose, as were 51.4% of those on rituximab, 50.8% of those taking etanercept, 50% of those on abatacept, 43.1% of those given tocilizumab, 29.2% of those on infliximab, and 13.6% of those on golimumab.

Among the 140 patients in the reduced-dose group, 11 were able to lower the biologic dose by more than 50%, 39 reduced it by 50%, and 75 reduced the dose by less than 50%. Those who experienced a relapse while on a reduced dose did so at a mean time of 1.9 years after the reduction.

The researchers also examined the cost impact of dose reduction, finding these annual cost differences between full and reduced doses:

• Rituximab: $9,527 vs $5,070
• Etanercept: $10,660 vs $6,052
• Adalimumab: $13,585 vs $7,783

Factors that might contribute to cost reductions include the specific medication's half life and insurance reimbursement. For example, the reimbursed dosage for infliximab is only for 3 mg every 8 weeks, and reducing that already low dose further might encourage the development of antidrug antibodies.

A limitation of the study was its retrospective design, according to the authors. "Further large prospective trials in daily clinical practice are needed to confirm the benefits of this [reduced-dose] approach for patients, physicians, and payers," they concluded.

Durez and co-authors disclosed no relevant relationships with industry.

Primary Source: Arthritis Research & Therapy: Dierckx S, et al "Tapering of biological antirheumatic drugs in rheumatoid arthritis is achievable and cost-effective in daily clinical practice: data from the Brussels UCLouvain RA cohort" Arthritis Res Ther 2020; DOI: 10.1186/s13075-020-02165-4.