ABSTRACT
BackgroundJanus kinase inhibitors (JAKinibs) have demonstrated efficacy in the treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA), although their safety profile continues to be analysed due to the possible increase in adverse events (AEs) in relation to anti-TNFs (mild and severe infections, haematological alterations, thromboembolism, increase in neoplasms).ObjectivesTo evaluate in real clinical practice the AEs of JAKinibs in a cohort of patients with RA and SpA. In addition, adherence and reasons for discontinuation (1st or 2nd failure, AE) are analysed.MethodsObservational study of 116 patients diagnosed with RA or SpA who received treatment with JAKinibis (tofacitinib, baricitinib, upadacitinib) after failure of treatment with different classical synthetic (FAMEsc) or biological (FAMEb) disease-modifying drugs. The following data were analysed: demographic characteristics of the patients, years of disease progression, 1st or 2nd failures and AE.ResultsMean age was 52 years, with Baricitinib being older (60 years -SD 13.6), higher prevalence of females in all groups, and a disease progression time of about 10 years. Mean number of FAMEsc was 1.6 and mean number of FAMEb was 2,3 to Tofacitinib(Tofa), 2,76 to Baricitinib(Bari) and 4,4 to Upadacitinib(Upa). 71 (63%) patients had active corticosteroid therapy. The median treatment time with Tofa was 8.8 months, Bari 9.5 and Upa 2.4 months.Most frequent AEs with Tofa were urinary tract infections(UTI) (11.9%, 7 cases) and headaches (8.47%, 5 cases). There were 3 cases of herpes zoster (5.1%), one of which was recurrent, and 2 cases respectively of tachycardia and gastrointestinal intolerance (3.4%). With Baricitnib, 2(5%) cases of UTI and 2(5%) of influenza A were reported. Most frequent AEs related to Upadacitinb are gastrointestinal intolerance, labialis and facial herpes, anterior uveitis and recurrent UTI, with 1 case for each adverse event. There were 4 success with Baricitinib treatment: 2 due to severe COVID, 1 influenza A and 1 due to stroke. 17 patients had 1st failure to Tofa(28.81%), 8 to Bari20.0%) and 3 to Upa(18.75%);7(11.86%) and 2(5%) patients had 2nd failure to Tofa and Bari respectively, no with Upa.Mean CRP to Tofa-SD 18.9-was 17.19, 20-SD 22.7- to Bari and 24.2-SD 27.40- to Upa. Mean ESR-SD 15.3- was 25.4, -SD 26.4 and 44.3 -SD 32-, respectively. At 6 months, 36(62%) were continuing on Tofa, 22(56%) on Bari and 4(27%) on Upa. At 12 months, 27(46.6%) were still on Tofa and 12 on Bari(30.8%) and no patients were on upa.Table 1.TofaBariUpaMean age496047Male19%18%20%Female81%82%80%Time course of disease(years)81111Permanence 6 months62%56%27%Permanence 12 months46,6%31%0%Patients with corticotherapy62%64%60%Previous biological drugs2,3 SD 22,8 SD 2,34,4 SD 2,9Patients who discontinued the drug62%59%33%Mean CRP at the end of treatment172024Mean end-of-treatment ESR252644Repeated AEsUTI(7) Headache(5) Shingles(3) Nephritic colic(2) Gastrointestinal intolerance(2) Tachycardia(2)UTI(4) Headache(2)Serious AEsShingles (3)Varicella encephalopathy(1) Stroke(1) Shingles (1)1st failure28,8%20%18,7%2nd failure11,9%5%0%SuccessSARS-Cov2(2) Influenza(1) Stroke(1)Figure 1. Months stay pharmacoConclusionMost frequent adverse events with JAKinibs are mild infections, except gastrointestinal complaints with upadacitinib. Serious adverse events, including 3 deaths from viral infections, were observed, mostly in patients over 65 years. Most frequent cause of discontinuation was treatment failure. We believe that further observational studies are needed to stratify and profile the risk of infection with JAKinibs.References[1]Atzeni F, Popa CD, et al. Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events. Expert Rev Clin Immunol. 2022 Mar;18(3):233-244. Doi: 10.1080/1744666X.2022.2039630 Epub 2022 Feb 17.PMID: 35129033[2]Alves C, Penedones A,et al. The Risk of Infections Associated With JAK Inhibitors in Rheumatoid Arthritis: A Systematic Review and Network Meta-analysis. J Clin Rheumatol. 2022 Mar 1;28(2):e407-e414 PMID:33902098Ackn wledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
Background: Interstitial Lung Disease (ILD) is the most common lung involvement in rheumatoid arthritis (RA) and leads to increased morbidity and mortality. Some retrospective observational studies suggest that abatacept (ABT) could be effective and safety, although there are no clinical trials and prospectively collected data are scarce. Objectives: To evaluate prospective the effectiveness and safety of ABT in patients with ILD associated RA (ILD-RA). Methods: Design and Protocol: We performed a multicenter, prospective, observational study of patients with interstitial lung disease secondary to rheumatoid arthritis (ILD-RA) receiving ABT between 2015 and 2021. The patients were assessed using high-resolution computed tomography and lung function tests at the beginning of treatment (V0), at 12 months (V12), and at the end of follow-up in 2021 (fV). The study was approved by the Ethics Committee (Code 1719-N-15). Main variable: effectiveness of ABT according to evolution of ILD at the end of follow-up: (1) improvement (ie improvement of FVC ≥10% or DLCO ≥15% and no radiological progression), (2) no progression (stabilization or improvement in FVC ≤ 10% or DLCO <15% and no radiological progression), (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression) or (4) death. Other variables: clinical and analytical characteristics, treatments and safety (infections, hospitalization and mortality). Statistical analysis: Cox regression analysis to identify factors associated with worsening of ILD-RA treated with ABT. Results: Thirty-eight ILD-RA patients started ABT treatment during prospective follow-up. A total of 22/38 (57.9%) were men and the mean (SD) age was 66.1 (9.1) years. The mean (SD) evolution of ILD was 43.9 (30.0) months and the median (IQR) time with ABT was 17.0 (12.1-34.8) months. The baseline clini-cal-epidemiological characteristics and pulmonary progression of the patients are shown in Table 1. At the end of follow-up (fV) 28/38 (73.6%) had improvement/stabilization and 7/38 (18.4%) progressed and 3/38 (7.8%) of them died (COVID-19 pneumonia, respiratory infection and ILD progression, respectively). There were no signifcant differences in FVC (75.3 [8.7] vs 77.7 [14.6];p=0.775) or in FEV1 (83.9 [10.7] vs 84.7 [13.2];p=0.416) nor in the DLCO (61.0 [17.4] vs 60.7 [15.2];p=0.789) at the end of follow-up. There was a greater numberwith improvement/stabilization among the patients who were in combination with Methotrexate compared to those who were in monotherapy (83.3% vs 39.1%;p=0.046). The baseline variables that were independently associated with progression-mortality of ILD-RA in fV were: baseline FVC (OR [95% CI], 0.895 [0.805-0.996];p=0.042) and duration of ILD-RA (OR [95% CI], 1.204 [1.148-2.112;p=0.046]). Two patients discontinued ABT during follow-up due to insufficient joint and pulmonary response. Conclusion: More than half of the patients with ILD-RA treated with ABT manage to stabilize or improve their lung disease after a median follow-up of 17 months. Patients who worsen or die have lower baseline FVC values and ILD-RA with a longer evolution time.