Portuguese recommendations for the use of biological and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis - 2020 update.

OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Safety and Effectiveness of Biologic Disease-Modifying Antirheumatic Drugs in Older Patients with Rheumatoid Arthritis: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: The number of older patients with rheumatoid arthritis is increasing, but data on drug effectiveness and safety in these patients are scarce. This study assessed the effectiveness and safety of biologic disease-modifying antirheumatic drugs in older patients with rheumatoid arthritis. METHODS: This prospective cohort study was based on data recorded in the Rheumatic Diseases Portuguese Register (Reuma.pt). Treatment persistence, European League Against Rheumatism response at 6 and 12 months, and adverse events were compared between adult (age < 65 years), old (age 65-74 years), and very old (age ≥ 75 years) patients. RESULTS: In total, 2401 patients were included, of which 379 were old and 83 were very old. Older patients had higher disease activity at baseline (Disease Activity Score 28: 5.5 in adults, 5.7 in old patients, and 6 in very old patients; p = 0.02) and more comorbidities, with patients aged 65-74 years beginning biologic disease-modifying antirheumatic drugs later in the course of rheumatoid arthritis. Treatment persistence was similar in the three patient groups (p = 0.07). The European League Against Rheumatism response rates were comparable in the three groups at 6 months (81.6% of adults, 75.2% of old patients, and 81.8% of very old patients; p = 0.19), and inferior in old patients at 12 months. The proportion of patients who experienced adverse events was also similar in the three groups (21% of adults, 22.5% of old patients, and 22.9% of very old patients; p = 0.76), but the rate of serious adverse events was higher in old patients (1.94/100 patient-years) and very old patients (4.29/100 patient-years) compared with 1.03/100 patient-years in adult patients with rheumatoid arthritis (p < 0.05). CONCLUSIONS: Adults, old patients, and very old patients with rheumatoid arthritis benefit similarly from biologic disease-modifying antirheumatic drug treatments, although older patients have more active disease at baseline and more comorbidities. However, it is necessary to consider the risk of serious adverse events in older patients when prescribing a biologic.

Anti-müllerian hormone and ovarian reserve in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic immune-mediated inflammatory disease that affects predominantly females during childbearing age (Lateef and Petri Best Pract Res Clin Rheumatol 27(3):435-447, 2013). Fertility in SLE patients is considered to be normal (Clowse et al. Arthritis Care Res (Hoboken) 64(5):668-674, 2012; Ekblom-Kullberg et al. Scand J Rheumatol 38:375-380, 2009) but several known factors may negatively influence fertility. Immune mechanisms are also thought to be an important cause of premature ovarian senescence, characterized by reduced ovarian reserve markers such as anti-Müllerian hormone (AMH) (Oktem et al. Obstet Gynecol Surv 70(3):196-210, 2015; Bermas and Sammaritano Fertil Res Pract 1:13, 2015; Østensen Int J Clin Rheumtol 8(1):27-37, 2013; Ulug et al. Am J Reprod Immunol 72(1):85-88, 2014; Lawrenz et al. Lupus 20(11):1193-1197, 2011). We evaluated the ovarian reserve of women in reproductive age with SLE, by measuring AMH levels and we compared it to that of non-SLE women. We also analyzed the association of SLE disease characteristics with AMH levels. AMH levels were decreased in this population of SLE women, accounting for a high proportion of women with criteria for low ovarian reserve. Age and SLE damage were associated with abnormally lower AMH levels in our SLE patients. In this way, SLE may have a negative influence on the ovarian reserve.

Protein Quality Assessment on Saliva Samples for Biobanking Purposes.

Biobank saliva sample quality depends on specific criteria applied to collection, processing, and storage. In spite of the growing interest in saliva as a diagnostic fluid, few biobanks currently store large collections of such samples. The development of a standard operating procedure (SOP) for saliva collection and quality control is fundamental for the establishment of a new saliva biobank, which stores samples to be made available to the saliva research community. Different collection methods were tested regarding total volume of protein obtained, protein content, and protein profiles, and the results were used to choose the best method for protein studies. Furthermore, the impact of the circadian variability and inter- and intraindividual differences, as well as the saliva sample stability at room temperature, were also evaluated. Considering our results, a sublingual cotton roll method for saliva collection proved to produce saliva with the best characteristics and should be applied in the morning, whenever possible. In addition, there is more variability in salivary proteins between individuals than in the same individual for a 5-month period. According to the electrophoretic protein profile, protein stability is guaranteed for 24 hours at room temperature and the protein degradation profile and protein identification were characterized. All this information was used to establish an SOP for saliva collection, processing, and storage in a biobank. We conclude that it is possible to collect saliva using an easy and inexpensive protocol, resulting in saliva samples for protein analysis with sufficient quality for biobanking purposes.