An increased number of elderly patients with rheumatoid arthritis (RA) has been observed in the last years mainly due to the increase of life expectancy. In this group it is possible to include two different categories: patients with onset of RA in advanced age (60-65 years old), and patients with an early occurrence of RA aged with the disease. For all elderly patients many factors such as: comorbidities and polytherapy, extra-articular manifestations of RA, and the process of immune-senescence can increase frailty and difficulties for rheumatologist in management of RA. Although patients with late onset of RA frequently show more aggressive articular involvement and systemic manifestations, literature data suggest that rheumatologists tend to treat elderly patients less aggressively. Moreover, they delay treat to target approach with less frequent use of biologic drugs and prolonged use of steroids or NSAIDsThe improvement of knowledge about persistence of different drugs and associated patients' profiles could suggest more specific treatment strategies encouraging the correct management of RA elderly patients in clinical practice.
Objectives
Aim of the study was to evaluate the retention rate at two years of treatment with biologic or targeted synthetic (ts) DMARDs, namely TNF inhibitors, anti-IL6, anti-CD20, Abatacept and Janus kinases inhibitors (JAKis), in patients with RA who received a targeted therapy over 65 years of age.
Methods
Data were extracted from the GISEA registry (Gruppo Italiano Studio Early Arthritis), selecting RA patients in which biologic- or ts-DMARDs were prescribed over 65 years of age. Global persistence in therapy and 2-year retention rate were evaluated by mean of Cox regression. Then, a multivariate analysis was performed to evaluate factors associated to the discontinuation of the treatment.
Results
We analysed data of 1221 patients (F/M ratio 966/255). Therapies prescribed were: TNFis in 362 pts (29.6%), anti-IL6 in 199 pts (16.3%), JAKi in 304 pts (24.9%), anti-CD20 in 53 pts (4.3%), abatacept in 303 pts (24.8%). Median time of persistence in therapy was 181 weeks (confidence interval 95% 158-205), with a significant difference among different classes of drugs (abatacept 254 weeks, CI95% 219-289; anti-CD20 221, 104-337; TNFis 184, 151-217; JAKis 139, 115-164; and anti-IL6 136, 105-167; p<0.001). Retention rate at two years was 66.3%± 3.8 for abatacept, 59.7%± 8.8 for anti-CD20, 54.9%± 3.7 for TNFis, 49.2%±0.5 for anti-IL6, 52.7%±3.7 for JAKis (Figure 1). A multivariate analysis including age, gender, class of drug, line of treatment, disease activity index on 28 joints (DAS28) was performed. Anti-citrullinated peptides antibodies, rheumatoid factor, combination therapy with glucocorticoids or methotrexate were excluded from the model, since not significant at univariate analysis. Multivariate analysis revealed that treatment with TNFis (HR 1.63 CI 1.01-2,63, p=0.044), treatment with anti-IL6 (HR 1.43 CI 1.11-1.85, p=0.006), an increase of 1 point of DAS28 (HR 1.21 CI 1.08-1.35, p=0.001) correlated with lower retention rate at two years. Among 1220 pts considered, 33.5% discontinued therapy. The most frequent cause of discontinuation for all drugs was a secondary loss of efficacy in 49.3% of cases.
Conclusion
In our study abatacept resulted the drug with the highest retention rate among drugs prescribed in elderly patients. On the other side, anti-IL6 showed the lowest persistence. Disease activity and the therapeutic choice may influence the retention rate. Our results on a very large population represent interesting points to consider for the choice of treatment for elderly RA patients. Prospective studies should be advisable to confirm these data.
References
[1] Boots AM, et al Nat Rev Rheumatol. 2013 Oct 9(10):604-13 [2] Murata K et al Int J Rheum Dis. 2019 Jun;22(6):1084-1093. [3] Sugihara T. et al Mod Rheumatol. 2022 Apr, 32(3):493-499.
The treatment to adopt when (Interstitial Lung Disease)ILD is detected in Rheumatoid Arthritis (RA) patients has always been a matter of debate. The management and treatment of RA-ILD is challenging because there is still little information available on this topic, and the main literature comes from observational studies. No clinical trials have been dedicated to this topic, however its consideration is increasing in guidelines. There is relatively limited data on the use of JAKi in patients with RA-associated ILD.
Objectives
The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAKi in patients with RA-ILD.
Methods
We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centres from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months before the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests.
Results
We included 43 patients with RA-ILD, 23 males (53.48%) with median age (interquartile range, IQR) of 68.87 (61.46-75.78) treated with JAKi. Clinical and disease characteristics have been reported in Table 1. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing Capacity of Lung for Carbon Monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%) (Figure 1).
Conclusion
This study seems to confirm that JAKi therapy might be a safe therapeutic option for patients with RA-ILD.
References
[1]Manfredi, A.; Cassone, G.; Luppi, F.; Atienza-Mateo, B.; Cavazza, A.; Sverzellati, N.; González-Gay, M.A.; Salvarani, C.; Sebastiani, M. Rheumatoid Arthritis Related Interstitial Lung Disease. Expert Rev Clin Immunol 2021, 17, 485–497, doi:10.1080/1744666X.2021.1905524. [2]Holroyd, C.R.; Seth, R.; Bukhari, M.; Malaviya, A.; Holmes, C.; Curtis, E.; Chan, C.; Yusuf, M.A.; Litwic, A.; Smolen, S.; et al. The British Society for Rheumatology Biologic DMARD Safety Guidelines in Inflammatory Arthritis. Rheumatology (Oxford) 2019, 58, e3–e42, doi:10.1093/rheumatology/key208.
Poster: ESCR 2015 / P-0021 / Late Gadolinium Enhancement is useful not only in the heart: a new tool to reveal skeletal muscle involvement in idiopathic inflammatory myopathies by: G. Benedetti 1, A. Esposito1, M. Cava1, M. colombo1, G. A. Ramirez1, D. Velardo1, A. Manfredi2, E. Bozzolo1, S. Previtali1, P. Rovere Querini1, A. Del Maschio1, F. De Cobelli1; 1Milan/IT, 2Milano/IT
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by chronic symmetrical erosive synovitis and extra-articular manifestations, including interstitial lung disease (ILD), whose treatment is nowadays challenging due to high infectious risk and possible pulmonary iatrogenic toxicity. Janus kinase inhibitors, namely, tofacitinib, baricitinib, and upadacitinib, are the latest drug class for the treatment of RA with a good safety profile. We present the case of a patient with RA-ILD successfully treated with tofacitinib. A 52-year-old man was referred to our multidisciplinary clinic for rheumatic and pulmonary diseases for an active erosive seropositive RA and progressive ILD. Previous treatments were GC, hydroxychloroquine, methotrexate, etanercept, withdrawn after ILD detection, and tocilizumab, discontinued due to relapsing infections. After our evaluation, we proposed rituximab in addition to low-dose GC and hydroxychloroquine, ineffective on joint involvement. Therefore, we proposed tofacitinib which allowed us to control joint involvement, stabilize ILD improving respiratory symptoms, and manage the frequent infectious episodes that occurred initially. The short half-life and rapid-acting of tofacitinib are two helpful characteristics regarding this aspect. Despite limited data from randomized trials and real-life, tofacitinib could represent a safe therapeutic option for RA-ILD patients. Longitudinal studies are required to confirm this encouraging report.
Introduction. Acute exacerbation of interstitial lung disease (ILD) and COVID-19 pneumonia show many similarities, but also COVID-19 sequelae, mainly when fibrotic features are present, can be difficult to distinguish from chronic ILD observed in connective tissue diseases. Case Report. In 2018, a 52-year-old woman, was diagnosed with primary Sjogren's syndrome (pSS). The patient did not show respiratory symptoms, and a chest X-ray was normal. During March 2020, the patient was hospitalized for acute respiratory failure related to COVID-19 pneumonia. Three months later, follow-up chest high-resolution computed tomography (HRCT) showed ground glass opacity (GGO) and interlobular interstitial thickening. Pulmonary function tests (PFTs) showed slight restrictive deficit and mild reduction in diffusion lung of carbon monoxide (DLCO). The patient complained of asthenia and exertional dyspnoea. A multidisciplinary discussion including rheumatologist, pulmonologist, and thoracic radiologist did not allow a definitive differential diagnosis between COVID-19 persisting abnormalities and a previous or new-onset pSS-ILD. A "wait and see" approach was decided, monitoring clinical conditions, PFTs, and chest HRCT over time. Only 2 years after the hospitalization, improvement of clinical symptoms was reported; PFT also improved, and HRCT showed almost complete resolution of GGO and interlobular interstitial thickening, confirming the diagnostic hypothesis of long-COVID lung manifestations. Discussion. In the above-reported case report, 3 differential diagnoses were possible: a COVID-19-related ILD, a preexisting pSS-ILD, or a new-onset pSS-ILD triggered by COVID-19. Regardless of the diagnosis, the persistence of clinical and PFT alterations, suggested a chronic disease but, surprisingly, clinical and radiologic manifestations disappeared 2 years later.
