Can people with rheumatoid arthritis stop their medications?

Rheumatoid arthritis (RA) is a chronic autoimmune disease that requires long-term treatment with disease-modifying anti-rheumatic drugs (DMARDs
).
The key goal of treatment for RA is to achieve clinical remission
.
Clinical remission has become an achievable treatment goal
due to early diagnosis and treatment of the disease, wider use of DMARDs, and the implementation of rigorous on-target treatment strategies.
Currently, 40-50% of patients with RA can achieve a stable response
.
While this number indicates substantial progress in the management of RA disease, remission does not imply cure, and patients often need to continue long-term treatment
after they have achieved remission.
For patients with long-term remission with RA, whether the drug can be stopped and the impact of the drug on the disease has always been a concern of doctors and patients
.
A multicenter, randomized controlled clinical trial (RETRO) from Germany conducted a study of patients with RA who had sustained remission and was published in the October 2021 issue of Lancet Rheumatol.
(IF=8.
136).

Research Objectives:

To assess the effects of three different treatment strategies (maintenance/dose reduction/discontinuation) on disease recurrence in patients with RA who have sustained remission, and to explore the possibility of no drug remission

Study Design:

The RETRO study is a multicenter, prospective, randomized controlled, open-label trial involving 303 adult RA patients (duration of disease> 12 months, at least three follow-up visits in the past 6 months) from 14 centers in Germany, randomly divided into three groups: continuous treatment group, dose reduction group (50% dose) and discontinuation group (50% dose treatment for 6 months + discontinuation for 6 months), observed for a total of 12 months, followed up every 3 months, the primary endpoint is 12 months of relapse-free remission rate
。 In patients taking JAKi and rituximab, the dose reduction regimen was divided into halving (csDMARDs, hormones, tocilizumab) and prolonged dosing intervals (abatacept, TNFi), and recurrence was defined as DAS28-ESR>2.
6
.

Key Results:

:Snowflake: A total of 282 patients entered the trial: 93 patients in the continuous treatment group, 93 patients in the dose reduction group, and 96 patients in the discontinuation group; After 12 months of follow-up, a total of 173/282 (61%) patients maintained DAS28-ESR remission, and 109/282 (39%) patients experienced relapse, with recurrence rates of 17%, 43%, and 55% in the three groups, and median recurrence time of 30.
6, 24.
3, and 26.
1 weeks, respectively;

:Snowflake: The relapse-free survival rate at 12 months was highest in the continuous treatment group (81.
2%), followed by the dose reduction group (58.
6%), and the relapse-free survival rate was lowest in the discontinuation group at 43.
3%;

:snowflake: The risk ratio (HR) of recurrence in the dose reduction group was 3.
02 (p=0.
0003) compared with the continuous treatment group; The HR for recurrence in the discontinuation group was 4.
34 (p<0.
0001);

:snowflake: 85% of patients in each group were in remission or low disease activity at the visit, few patients had moderate-high disease activity due to relapse, and most resumed remission after restarting the original regimen with full-dose DMARDs;

:snowflake: higher recurrence rates in female, bDMARD use, positive autoantibodies, longer course of disease, higher baseline DAS28 and health assessment questionnaire scores;

Snowflake: Safety was comparable in all three groups, with the most common serious adverse event being injury or surgical complications (n=9), and none of them were considered related to pharmacological interventions or led to patient withdrawal from the study
.

Conclusion:

The study showed that drug reduction and discontinuation of patients with long-term deep remission led to a significantly increased risk of RA recurrence, but about 50% of patients can still maintain remission, and most patients with relapse restarted remission after restarting treatment, so it is feasible
to reduce the dose of drugs in patients with RA who are in stable response.

References:

Tascilar K, Hagen M, Kleyer A,et al.
Treatment tapering and stopping in patients with rheumatoid arthritis in stable remission (RETRO): a multicentre, randomised, controlled, open-label, phase 3 trial.
Lancet Rheumatol.
Published online October 1, 2021.
https://doi.
org/10.
1016/S2665-9913(21)00220-4