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INTRODUCTION: Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved to treat rheumatoid arthritis (RA). This study aimed to investigate patients' characteristics, prescription patterns, effectiveness, and treatment persistence in patients receiving baricitinib in real-world practice in Spain. METHODS: This retrospective longitudinal cohort study conducted in five rheumatology units included adults with RA initiating baricitinib (Sep-2017-May-19) with at least a 6-month-follow-up. Demographic/clinical characteristics, prescription patterns, and changes in disease activity and pain level were collected until treatment discontinuation/end of follow-up. Treatment persistence was estimated by Kaplan-Meier methods. RESULTS: Data from 182 patients were included (mean (SD)): 83.5% women, 62.2 (12.3) years, body mass index 26.8 (5.1), disease duration 13.2 (10.8) years and Charlson Comorbidity Index score 2.4 (2.0). All patients had received at least one conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) before starting baricitinib and 78.0% at least one biologic disease-modifying anti-rheumatic drugs (bDMARD). Furthermore, 90.1% started with baricitinib 4 mg/day; 43.4% in monotherapy. One hundred and twelve (61.5%) of patients continued baricitinib at data collection time; mean persistence was 14.1 (0.5) months. Overall treatment persistence was 79.7/64.8/59.1% at 6/12/18 months. Seventy (38.5%) patients discontinued baricitinib during follow-up due to loss of efficacy (68.6%) or adverse events (18.6%). In those patients with available scores at the different observed cut-off points, remission or low disease activity was reported in 71.6 and 76.3% of patients at 6/12 months at any index: Disease Activity Score 28 joints using erythrocyte sedimentation rate (DAS28-ESR) (73.1 and 73.5%), Simplified Disease Activity Index (SDAI) (62.4 and 75.0%), and Clinical Disease Activity Index (CDAI) (66.7 and 78.1%). Good or moderate European League Against Rheumatism (EULAR)-response was noted in 80.0 and 78.2% of patients, respectively. Improvement from baseline in pain (Visual Analog Scale) was 2.5 cm and 3.0 cm at 6/12 months, respectively. CONCLUSIONS: This Spanish cohort of patients treated with baricitinib had a long-standing and refractory disease. Nevertheless, high persistence and improvements in disease activity and pain were found at 6 and 12 months after treatment initiation, independently of the composite disease activity measure used, reinforcing the effectiveness of baricitinib in routine clinical practice.
ABSTRACT
Background: Gout is the most common type of inflammatory arthritis. Nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine are the first-line agents, although they are contraindicated in many patients. Blockade of IL-1 with anakinra can be an alternative. Objective: To present a case series of 10 difficult-to-treat gout patients treated with anakinra and perform a scoping review of the effectiveness and safety of anakinra in gout patients. Methods: A total of 1,519 citations were screened. The reviewers ran a two-stage screening process by title/abstract and full-text reading. Thirty-eight articles finally met the selection criteria and were included for data extraction and synthesis. Experience in difficult-to treat and complex clinical scenarios, such as active infection, hemodialysis, and transplantation, were specifically described. Results: The study sample comprised 551 patients, from whom 648 flares were finally analyzed. The mean age was 57.9 years, and 82.9% were men. The clinical presentation was polyarticular in 47.5% and tophaceous in 66.9%. Sixty-five patients with an active infection, 41 transplanted patients and 14 in haemodyalisis treated with anakinra are described. More than half of the patients had >1 associated comorbidity. Anakinra was effective both for flares (94%) and for long-term treatment (91%) and well tolerated. In the case of flares, 34 (6.7%) adverse effects were registered. Adverse events were more prevalent in long-term treatment. Conclusion: Anakinra was effective and safe for management of gout flares in difficult-to-treat patients. It has been used in multiple complex scenarios, such as active infections, dialysis, transplantation, chronic kidney disease, and polyarticular gout. Anakinra has also proven effective as long-term treatment, although there are more concerns about its safety.
ABSTRACT
OBJECTIVE: To study subclinical inflammation in intercritical gout patients and its relation to the estimated size of monosodium urate crystal deposition and cardiovascular risk factors. METHODS: We performed a secretome analysis and the quantification of cytokine and adipokine plasma levels [IL-1ß, IL-18, IL-6, soluble IL-6 receptor (sIL-6R), TNF-α, C-X-C motif chemokine 5, RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted), leptin, resistin and adiponectin] to analyse subclinical inflammation in intercritical gout patients. Since it is currently not feasible to determinate the whole body deposit of monosodium urate crystals, we created an indirect clinical classification to estimate it. Then we compared cytokine levels in controls and gout patients and in patients with different crystal deposition sizes. We also studied the association between cytokine-levels and the number of cardiovascular risk factors. RESULTS: Ninety consecutive patients attending a crystal arthritis unit were studied. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in intercritical gout patients than in controls. An association was observed between IL-18, sIL6-R and RANTES levels and the size of crystal deposition. IL-18, sIL6-R, RANTES and leptin were higher in patients with no cardiovascular risk factors compared with controls with no risk factors. CONCLUSION: Our results showed that the levels of some pro-inflammatory cytokines and metabolic proteins are elevated in intercritical gout patients. The levels of certain cytokines were related to the estimated size of the monosodium urate crystal deposition and to the number of cardiovascular risk factors. These cytokine changes may help to explain the increase in cardiovascular events in gout patients.
