Discussion

Our study demonstrated that a significant reduction in GC exposure could be achieved during the first six months following biologic therapy initiation in patients with RA, regardless of the treatment line. More than half of patients (31, 51.7%) achieved a GC dose of ≤5 mg/day, reflecting a substantial GC-sparing effect of biologic therapies in routine clinical practice. The mean GC dose decreased from 8.74 ± 1.93 mg/day at M0 to 6.07 ± 2.07 mg/day at M6. However, complete GC withdrawal remained uncommon, occurring in only one patient (1.7%). Baseline DAS28-CRP was significantly lower in patients who achieved a GC dose ≤5 mg/day at M6 than in those who remained on >5 mg/day (4.82 ± 0.77 vs. 5.36 ± 0.96, p = 0.02). The low rate of complete GC withdrawal observed in our study may be explained by the relatively short follow-up period, the long-standing nature of RA in our cohort, previous biologic exposure, and the high prevalence of comorbidities such as fibromyalgia. These findings highlight that although biologic therapies facilitate GC tapering, complete discontinuation remains challenging to achieve in a substantial proportion of patients. Nevertheless, the observed reduction in GC dose is clinically relevant, as it may reduce the risk of GC-related adverse effects and is consistent with current EULAR recommendations to minimize GC exposure whenever possible.

The challenges associated with GC withdrawal observed in our cohort have also been highlighted in the SEMIRA trial [11]. Although GC tapering was feasible in a substantial proportion of patients with well-controlled RA receiving biologic therapy, maintenance of low-dose prednisone (5 mg/day) was associated with better disease control and fewer disease flares compared with complete withdrawal. Overall, our findings are consistent with those of the SEMIRA trial, supporting the feasibility of GC dose reduction while highlighting the persistent challenges of achieving complete discontinuation despite effective biologic treatment.

Evidence from the international TOCERRA and PANABA collaborative studies further supports our observations. In these large international TOCERRA and PANABA collaborative cohorts, GC use decreased significantly following initiation of TNF inhibitors, tocilizumab, or abatacept. Nevertheless, the median time required to achieve complete GC withdrawal remained approximately two years or longer in most countries, emphasizing the persistent difficulties of complete GC withdrawal despite effective biologic therapy [13]. Similarly, complete withdrawal remained uncommon at M6 in our cohort despite a significant reduction in GC doses.

Additional evidence comes from the recent STAR trial, which compared two GC withdrawal strategies in patients with RA and low disease activity. Despite a structured tapering protocol and stable disease control, only 47% to 55% of patients achieved complete GC withdrawal after 12 months [14]. These results confirm that, even under optimized management conditions, successful GC withdrawal remains difficult to achieve.

Similar observations have been reported in real-world cohorts of patients receiving biologic therapy. In a study of patients with low disease activity treated with stable biologic or targeted synthetic DMARD therapy, 54% successfully achieved GC tapering. In contrast, complete prednisone discontinuation was observed in only 33% of cases. These findings further illustrate the gap between treatment recommendations and routine clinical practice and are consistent with the low rate of complete GC withdrawal observed in our study [15].

One possible explanation for the persistence of low-dose GC therapy in our cohort relates to the increased risk of flare associated with intensive tapering strategies. Adami et al. reported that tapering GCs to doses ≤2.5 mg/day or complete discontinuation was associated with a significantly increased risk of flare in patients receiving biologic therapy, whereas tapering to doses >2.5 mg/day was not associated with a significantly higher flare risk [16]. These findings suggest that maintaining low-dose GC therapy may contribute to disease stability in selected patients and may partly explain the limited rate of complete GC withdrawal observed despite significant improvement in disease activity.

The clinical relevance of the 5 mg/day prednisone threshold deserves particular attention. The GLORIA trial [12], conducted in elderly patients with RA, demonstrated that the addition of low-dose prednisolone (5 mg/day) resulted in improved disease control and reduced radiographic progression compared with placebo. However, these benefits were accompanied by an increased incidence of adverse events, particularly infections and other GC-related complications. These findings suggest that although a daily prednisone dose of 5 mg may contribute to maintaining disease control, it cannot be considered entirely risk-free. In our study, more than half of the patients achieved a GC dose ≤5 mg/day at M6, whereas complete GC withdrawal remained uncommon. Together, these findings highlight the clinical challenge of balancing optimal disease control with minimization of long-term GC exposure.

Our findings are further supported by the study of Spinelli et al. [17], which evaluated GC tapering and discontinuation in patients with RA treated with tofacitinib. The authors reported that a substantial proportion of patients were able to discontinue GCs as early as week 12 following treatment initiation, with approximately one-third achieving complete GC withdrawal during follow-up. These findings suggest that, despite the effectiveness of targeted therapies, complete GC withdrawal remains challenging in a considerable proportion of patients. This observation is consistent with our results, where a significant reduction in GC doses was achieved, whereas complete withdrawal was observed in only one patient.

Additional evidence supporting the GC-sparing effect of biologic therapies comes from the SPARE-1 study [18], which evaluated patients with RA treated with tocilizumab while receiving more than 5 mg/day of prednisone. After 12 months of treatment, 40% of patients achieved a GC dose below 5 mg/day without intensification of their disease-modifying therapy. However, complete GC withdrawal remained difficult to achieve, highlighting that dose reduction is often more feasible than full discontinuation. These findings further emphasize the persistent challenges associated with GC withdrawal despite effective control of disease activity with biologic therapies.

Strengths and limitations

To our knowledge, this is among the few longitudinal studies specifically evaluating the GC-sparing effect of biologic therapy in patients with RA in routine clinical practice in Morocco. The longitudinal design allowed for standardized data collection at predefined time points (M0, M4, and M6) and enabled assessment of GC dose evolution over time. Additionally, the inclusion of two biologic treatment groups (rituximab and anti-TNF agents) provided an opportunity to compare GC-sparing outcomes between different therapeutic classes. Furthermore, the concomitant assessment of disease activity (DAS28 and SDAI), inflammatory markers, pain intensity, and functional status strengthened the clinical relevance and interpretation of the observed results.

However, some limitations should be acknowledged. First, this was a single-center observational study with a relatively limited sample size, which may restrict the generalizability of the findings. Second, the follow-up period was limited to six months and therefore did not allow evaluation of the long-term sustainability of GC reduction or the maintenance of complete GC withdrawal. Finally, GC tapering strategies were not standardized. Additionally, no multivariable analysis was performed to identify independent predictors of successful GC tapering.