Very low dose glucocorticoid therapy in rheumatoid arthritis: Impact of b/tsDMARDs initiation timing on glucocorticoid withdrawal.

OBJECTIVES: We investigated the effectiveness and safety of very low-dose (<5 mg daily) glucocorticoids (GCs) in patients with RA treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very low-dose GCs on safety was also evaluated. RESULTS: We enrolled 229 RA patients, of whom 68% were prescribed very low-dose GCs and 32% received no GCs. After three years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off, and 23% had permanently discontinued very low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very low-dose GCs cessation (OR 1.1, 95% CI 1.03-1.14 for any 1-year decrease; p= 0.001). A significant association existed between ongoing utilization of very low-dose GCs and persistent moderate disease activity. Use of very low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%). CONCLUSION: A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.

Controversies in in rheumatology and autoimmunity: Is CORA meeting a good educational tool to increase the scientific knowledge?

Rheumatology and Autoimmunity are closely related fields and are among the most exciting areas in Medicine. Many conditions once regarded as mysterious and incurable are better understood and managed nowadays. Part of the great interest in these subjects derives from the fact that many controversial issues have arisen due to the rapid progression of knowledge, which means they are debatable. Over the years, the Controversies in Rheumatology and Autoimmunity (CORA) meetings promoted critical discussions not as an end but as a tool to increase the scientific knowledge of Rheumatologists and Clinical Immunologists. Beyond pursuing knowledge, being critical means questioning our inveterate beliefs and evaluating new conjectures and hypotheses. Thus, the approach to the debates in Medicine should be done with an open mind and free from all prejudices. Freedom of thought and speech are the fundamental values of our University, as exemplified by the motto "Universa Universis Patavine Libertas" which means "Padua freedom is universal for everyone". Patavine libertas initially referred to freedom from political and religious power but also freedom in research and teaching. For these reasons, Galileo Galilei moved to Padua in 1592, where he spent the most prosperous years of his life before being accused of heresy by the catholic church. We aim for the CORA congress to be an open-minded forum where active participation and exchange of ideas are promoted without prejudice. This special Issue of Autoimmunity Reviews is devoted to some controversies debated during the 7th CORA conference held in Turin, Italy, on March 16-18, 2023. Here we will discuss controversial entities, the use of old and new drugs, and insights into the classification, assessment of disease activity, and management of rheumatic diseases.

To treat or not to treat rheumatoid arthritis with glucocorticoids? A reheated debate.

The therapeutic landscape of rheumatoid arthritis (RA) has rapidly evolved in the last few decades. At the same time, recommendations for the management of the disease suggest to minimize glucocorticoids (GCs) use in RA patients. Major concerns are the risk of long-term adverse events and the difficulties in discontinuing GCs once initiated. However, real-world data show that up to 50% of RA patients continue to take GCs during the disease course. Adverse events of GCs usually occur after a long-term use, which can limit the generalizability of randomized controlled trials (RCTs) proving no or minimal harm. Observational studies show conflicting results regarding the safety of GSs and are subjected to a high risk of bias, including indication bias. Thus, whether or not GCs should be used in the management of RA is still a matter of debate. The main reasons to support GCs use are the ability to rapidly suppress joint inflammation while waiting for the full effect of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and the acknowledged efficacy on radiographic progression in early RA. The main reasons to avoid GCs use in RA are that their potential risks may outweigh their benefits and there is no agreement on the minimal daily dosage of GC which can be considered safe.

Early characterization of difficult-to-treat rheumatoid arthritis by suboptimal initial management: a multicentre cohort study.

OBJECTIVES: To demonstrate that unsuccessful treatment optimization in early disease is associated with difficult-to-treat RA (D2T-RA). METHODS: In this retrospective multicentre cohort study conducted from 09/2021-03/2022, we enrolled individuals fulfilling the 2010 ACR/EULAR RA criteria diagnosed 2000-2019. The outcome was D2T-RA by the EULAR definition. We used robust regression to examine the associations with delay, dose, duration of methotrexate and discontinuation of glucocorticoids. We tested through multinomial regression which factors were associated with persistent inflammatory refractory RA (PIRRA) or non-inflammatory refractory RA (NIRRA). Sensitivity analysis included a case-control study matching the year of diagnosis. RESULTS: We enrolled 48 D2T-RA patients and 145 non-D2T-RA controls. Methotrexate was started within 3 months in 16.7% of D2T-RA vs 33.1% of non-D2T-RA (P = 0.011). Adequate duration of methotrexate was obtained in significantly fewer D2T-RA patients (70.8% vs 85.5%). Glucocorticoids were continued beyond 6 months in a higher proportion of D2T-RA patients (70.8% vs 33.8%, P < 0.001). In multiple regression, treatment delay beyond 3 months (OR 0.3; 95% CI 0.1, 0.9) and non-discontinuation of glucocorticoids after 6 months (OR 4.6; 95% CI 2.2, 9.5) were significantly associated with D2T-RA. Treatment delay was significantly associated with PIRRA only, while non-discontinuation of glucocorticoids was significantly associated with PIRRA and NIRRA. Results were replicated in sensitivity analyses. CONCLUSION: Failure to start methotrexate within 3 months and not being off glucocorticoids within 6 months are early predictive features of D2T-RA.

Duration of clinical remission and low disease activity impacts on quality of life and its domains in psoriatic arthritis patients: results from an Italian multicentre study.

OBJECTIVES: Long-term quality of life (QoL) is significantly compromised in patients with psoriatic arthritis (PsA) and only partially improves achieving remission or low disease activity. The main aim of this study is to evaluate the QoL in PsA patients and to investigate their possible relationship with clinical remission and low disease activity, and with its duration over time. METHODS: A multicentre cross-sectional observational study has been performed. QoL domains considered were analysed through PROs. Chi2 test was used for analysis of contingency tables, while Mann-Whitney test and Kruskal-Wallis test with Holm's pairwise comparison corrections were used to compare ranks. To evaluate variables associated to the different QoL domains, univariate and multiple linear regressions were used. RESULTS: 143 participants were included in this study. The physical component of the Short Form-36 or Functional Assessment of Chronic Illness Therapy-Fatigue tends to improve with short duration of low or minimal disease activity. However, this is not confirmed for the mental component of SF-36 (MCS), which improved only with longer duration of low/minimal disease activity. CONCLUSIONS: This study proves the existence of an inverse relation between disease activity and QoL domains. Apart from low or minimal disease activity, also its persistence over time has a great influence on the patient's perception of their clinical condition; therefore, persistence over time of clinical remission/low disease activity should be added to the latest definition of treat-to-target in PsA.