Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01–5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19–8.66) and 12 months (OR = 6.62; 95% CI = 1.25–46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01–2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02–1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01–1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98–0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46–523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02–0.47), monotherapy (OR = 19.22; 95% CI = 2.05–343.00), lower initial patient’s visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92–0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87–0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results.

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of unknown etiology which causes progressive deterioration of the joints, leading to severe pain and functional disability. Vitamin D and its receptor (VDR) play a significant part in the onset of autoimmune diseases such as RA. The purpose of this study was to evaluate the association between VDR gene polymorphisms and risk of developing RA.Material and methodsA retrospective study was performed, including 214 RA cases and 748 controls of Caucasian origin. FokI (rs2228570), BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232) and Cdx2 (rs11568820) gene polymorphisms were analyzed by TaqManResultsThe recessive logistic regression model showed that the VDR FokIAA genotype was associated with lower risk of RA (p = 0.0255; OR = 0.58; 95% CI: 0.35–0.92). No other genetic polymorphism showed any association with RA in any of the models tested. Haplotype analysis revealed that the haplotypes ACGAG (p = 0.033; OR = 1.62; 95% CI: 1.04–2.53) and GTGCA (p < 0.01; OR = 2.77; 95% CI: 1.53–4.98) for BsmI, Cdx2, FokI, ApaI and TaqI were associated with higher risk of RA.ConclusionsVDR FokI gene polymorphism showed a trend for risk of RA, taking into account the variables of gender, age and tobacco use, and preventing false positives. Among our patients we found no influence of VDR BsmI, TaqI, ApaI and Cdx2 on the risk of developing RA. However, haplotype analysis indicated that the haplotypes ACGAG and GTGCA were associated with higher risk of RA.

Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in these patients. The objective of our study was therefore to investigate the role of polymorphisms of the CTLA-4, CD80 and CD86 genes, as well as that of clinical factors of the disease, in the response to ABA in patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan® probes. The patients were classified according to the European League Against Rheumatism (EULAR) criteria at 6 and 12 months from start of treatment. The independent variables associated with higher EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower baseline patient’s visual analogue scale (PVAS) after 12 months. In addition, a significant association was found between duration of ABA treatment, non-administration of concomitant glucocorticoids and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical variables, with remission of the disease after 6 months’ treatment with ABA. Finally, remission of the disease after 12 months’ treatment with ABA was associated with earlier age at start of ABA therapy and lower number of previous biologic therapies (BTs). The CTLA-4rs5742909-T allele and the CTLA-4rs231775-G allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months’ treatment with ABA (CTLA-4rs5742909 T vs. CC; OR = 5.88; CI95% = 1.48–23.29 and OR = 4.75; CI95% = 1.35–17.94, respectively, and CTLA-4rs231775 G vs. AA, OR = 3.48; CI95% = 1.20–10.09 and OR = 4.68; CI95% = 1.49–17.94, respectively). In conclusion, patients with RA treated with ABA showed better EULAR response and LDA rate when they had the CTLA-4 rs5742909-T or CTLA-4 rs231775-G polymorphisms; furthermore, this remission rate increased in patients that began ABA treatment earlier, those with a lower number of previous BTs and those with a lower PVAS value.

IntroductionMethotrexate (MTX) is the treatment of choice for patients with rheumatoid arthritis (RA). However, it has been found to produce toxicity in some patients. Different polymorphisms can play a part in inter-individual differences in toxicity. Our aim is therefore to determine the influence of gene polymorphisms in the MTX metabolic pathway, such as MTHFR (rs1801133 and rs1801131), MTHFD1 (rs2236225), MTR (rs1805087), and ABCC2 (rs4148396), on toxicity in MTX treatment among Caucasian patients diagnosed with RA.Material and methodsReal-time polymnerase chain reaction (PCR) analysis with TaqMan probes was performed on these polymorphisms in 200 patients in a retrospective study.ResultsPatients with TT genotype and C allele for MTHFR rs1801133 gene polymorphism presented a higher risk of anaemia (p = 0.0304; OR = 3.70; 95% CI: 1.10–12.34) and dizziness (p = 0.0438; OR = 8.15; 95% CI: 1.61–148.68). Patients with MTHFR rs1801131-C allele or CC genotype presented a higher risk of mucositis (p = 0.0188; OR = 3.02; 95% CI: 1.22–7.91), acneiform rash (p = 0.0322; OR = 5.74; 95% CI: 1.34–39.21), and alopecia (p = 0.0072; OR = 5.11; 95% CI: 1.37–17.70). Patients with MTR rs1805087-CC genotype presented a higher risk of anosmia (p = 0.0038; OR = 98.00; 95% CI: 3.16–infinite); patients with the TT genotype or T allele for MTHFD1 rs2236225 presented a higher risk of liver failure (p = 0.00229; OR = 2.34; 95% CI: 1.14–4.96) and alopecia (p = 0.0248; OR = 3.83; 95% CI: 1.10–13.30), and patients with the TT genotype for ABCC2 rs4148396 polymorphism (p = 0.0466; OR = 2.67; 95% CI: 0.98–6.94) presented a higher risk of headaches.ConclusionsPharmacogenomic analysis of these polymorphisms may facilitate decision-making in relation to MTX treatment toxicity among RA patients.

underwent surgery twice for wound debridement and samples were taken. After 6 days of empirical treatment, microbiological culture of exudate revealed Streptococcus pyogenes, and directed antibiotic therapy with penicillin and clindamycin was given. Skin lesions improved progressively with the treatment and lymphocyte count was 1.12×10×3/mL. However, he had to undergo plastic surgery for loss of granulated substance in the affected tissue. Clindamycin was suspended after 7 days and penicillin G after 14 days of treatment. One month later, a significant improvement in cutaneous injuries caused by baricitinib was observed, although he continued to need daily cures for sequels. Conclusion and relevance This adverse reaction was reported to the pharmacovigilance centre and caused baricitinib discontinuation. Immunosuppression caused by baricitinib and probable subsequent infections should be taken into account when starting this treatment in susceptible patients.

was 70 (57-83) years. Background: 50% had arterial hypertension, 37.5% heart disease, 25% diabetes, 25% chronic obstructive pulmonary disease and 12.5% active neoplasia. The diagnosis was severe pneumonia in all cases. The average duration of hospitalisation was 29 (4-73) days. 50% of patients were admitted to the ICU and required mechanical ventilation. In 75%, the dose was 600 mg and the rest required 400 mg, all single doses. The average time from symptom onset to drug administration was 15 (10-30) days. Concomitant drug therapy for SARS-CoV-2: 100% hydroxychloroquine with azithromycin, 87.5% lopinavir/ritonavir, 37.5% methylprednisolone boluses, 25% oral methylprednisolone and 12.5% interferon-ß-1b. 87.5% of patients were discharged. No adverse reactions were reported. Conclusion and relevance Treatment with tocilizumab could be considered a safe and effective option in patients with severe SARS-CoV-2 pneumonia. Further studies are necessary to confirm these preliminary results. Adjustment of the treatments to the criteria established by the regulatory agencies and the recording of health outcomes could contribute to more efficient therapies.

was 70 (57-83) years. Background: 50% had arterial hypertension, 37.5% heart disease, 25% diabetes, 25% chronic obstructive pulmonary disease and 12.5% active neoplasia. The diagnosis was severe pneumonia in all cases. The average duration of hospitalisation was 29 (4-73) days. 50% of patients were admitted to the ICU and required mechanical ventilation. In 75%, the dose was 600 mg and the rest required 400 mg, all single doses. The average time from symptom onset to drug administration was 15 (10-30) days. Concomitant drug therapy for SARS-CoV-2: 100% hydroxychloroquine with azithromycin, 87.5% lopinavir/ritonavir, 37.5% methylprednisolone boluses, 25% oral methylprednisolone and 12.5% interferon-ß-1b. 87.5% of patients were discharged. No adverse reactions were reported. Conclusion and relevance Treatment with tocilizumab could be considered a safe and effective option in patients with severe SARS-CoV-2 pneumonia. Further studies are necessary to confirm these preliminary results. Adjustment of the treatments to the criteria established by the regulatory agencies and the recording of health outcomes could contribute to more efficient therapies.

Background:Concomitant use of methotrexate (MTX) in abatacept (ABA) therapy is associated with good clinical response in patients with rheumatoid arthritis (RA) who are naïve to biological disease-modifying antirheumatic drugs (bDMARDs)1,2. However, it is unclear when abatacept is used in patients with prior bDMARDs use3.Objectives:We compared the effectiveness of abatacept monotherapy versus abatacept combined with methotrexate therapy in rheumatoid arthritis patients with prior bDMARDs use.Methods:Retrospective cohorts study. Rheumatoid arthritis patients treated with abatacept between 2009 and 2019 (n=86). Socio-demographic, clinical and pharmacological characteristics of patients were collected. We compared clinical effectiveness between ABA monotherapy patients (n=49) and abatacept concomitant methotrexate therapy patients (n=37), prior treated with bDMARDs. The effectiveness was measured according toThe European League Against Rheumatism(EULAR) response withDisease Activity Score(DAS28) like satisfactory (DAS28<3.2) or unsatisfactory (DAS28≥3.2), after 12 months of ABA therapy in RA patients.Results:49 RA patients have been evaluated in ABA monotherapy group; 83.67% (41/49) were women, disease duration was 16 (10-22) years and age of RA diagnosis was 48 (38.25-57.00). Concomitants glucocorticoids were administrated in 81.63% (40/49). Rheumatoid factor (RF) was positive in 75.51% (37/49) patients and cyclic citrullinated peptide antibodies (ACPA) in 71.43% (35/49). At 12 months, 40.82% (20/49) of patients had satisfactory EULAR response.In the combination therapy group, the age of RA diagnosis was 42.5 (35.75-53.50), 75.68% (28/37) were women and the disease duration was 12 (7-21) years. 89.19% (33/37) had concomitants glucocorticoids and the RF was positive in 72.97% (27/37) of patients. EULAR response was satisfactory at 12 months in 43.24% (16/37) of patients. No difference in treatment effectiveness was found in patients receiving abatacept in combination therapy with MTX compared with ABA monotherapy (p=0.829; IC95=0.35-2.35).Conclusion:Abatacept plus methotrexate therapy did not improve the effectiveness in rheumatoid arthritis patients with prior bDMARDs use, compared with abatacept monotherapy.References:[1]Genovese M, Schiff M, Luggen M, Becker J, Aranda R, Teng J, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Annals of the rheumatic diseases. 2008;67(4):547-54.[2]Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020.[3]Walker UA, Jaeger VK, Chatzidionysiou K, Hetland ML, Hauge E-M, Pavelka K, et al. Rituximab done: what’s next in rheumatoid arthritis? A European observational longitudinal study assessing the effectiveness of biologics after rituximab treatment in rheumatoid arthritis. Rheumatology. 2016;55(2):230-6Disclosure of Interests:None declared