Effectiveness of Baricitinib in Refractory Seronegative Rheumatoid Arthritis and Uveitis: A Case Report

Baricitinib is a Janus kinase (JAK) inhibitor used to treat refractory rheumatoid arthritis and blocks the subtypes JAK1 and JAK2. A 35-year-old man with seronegative rheumatoid arthritis complicated by bilateral severe non-granulomatous panuveitis was resistant to steroid treatment, multiple conventional disease-modifying antirheumatic drugs (methotrexate and salazosulfapyridine), and TNF-α inhibitors (adalimumab and infliximab). Therefore, the TNF-α inhibitors were switched to baricitinib to decrease the activity of systemic arthritis. Along with the amelioration of inflammatory activity in seronegative rheumatoid arthritis, the inflammatory activity of uveitis was decreased. Vitreous opacity, serous retinal detachment, and anterior chamber cells showed improvement. Baricitinib was effective not only in refractory systemic arthritis but also in uveitis, which may provide a new treatment option for patients with refractory uveitis.

The Efficacy of Sequential Biologic Agents in Refractory Rheumatoid Arthritis after Failure of Initial DMARD and anti-Tumor Necrosis Factor Therapy

Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent had failed in this open-label observational study. These patients were all treated with a second biologic agent and 27 ultimately required treatment with a third. The response to the therapy and disease activity were assessed at 6 and 12 months after each switch. Results: The remission rates at 6 months were lower than previously reported and the initiation of a second biologic agent resulted in significant improvement at 12 months, including DAS remission in 36% of patients. The response in those receiving a third biologic was less pronounced, as might be expected in this relatively treatment-refractory population. In this group, only patients treated with tocilizumab had maintained remission at one year. Conclusion: Patients who do not respond to an anti-TNF agent often benefit from being switched to a second, or even third, biologic. Importantly, it may take longer than expected to fully assess the effectiveness of a second or third agent in patients with refractory disease.

Photodynamic therapy for synovial hyperplasia in patients with refractory rheumatoid arthritis: a study protocol for a randomized, double-blind, blank-controlled prospective trial

Background Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis. Methods and analysis This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the “PDT once” group, and the “PDT twice” group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively. Ethics and dissemination The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital. Trial registration number ChiCTR1800014918.

AB0225 TUMOR NECROSIS FACTOR ALPHA (TNF-Α) INHIBITORS IN PATIENTS WITH REFRACTORY RHEUMATOID ARTHRITIS: REASONS FOR WITHDRAWAL

Background:Refractory rheumatoid arthritis (RRA) is a subtype of rheumatoid arthritis (RA), in which the sequential administration of optimal methotrexate doses in combination with glucocorticoids, and at least - two biologic disease-modifying antirheumatic drugs (bDMARDs) with different mechanisms of action during 18-24 months does not lead to a significant decrease in the inflammatory activity of RA.Objectives:to determine the reasons for the withdrawal of TNF-α inhibitors in patients with RRA.Methods:The retrospective study included data of 95 RRA patients (80 females, 80.8%), aged 23 to 80 years (mean age 57 years), treated with TNF-α inhibitors. Mean RA duration was 11.9±7.6 years. All patients were divided into 6 groups depending on the number of the lines of therapy received. A total of 154 cases of TNF-α were studied.Results:Infliximab (INF) was most often prescribed as the first line of therapy - 40 prescriptions. The reasons for the withdrawal of INF as the first bDMARDs were: insufficient effectiveness (IE) - 20 cases (50% of appointments), administrative reasons (AdmR) - 13 cases (32.5% of appointments), adverse reactions (AR) - 6 cases (15% of appointments), remission - 1 case (2.5% of appointments). In the 2nd line of therapy, INF was prescribed in only 3 cases, the drug was canceled in all cases due to IE. In 3 lines of therapy, INF was prescribed in 4 cases, the reasons for withdrawal in these cases were IE (50%, 2 cases) and AR (50%, 2 cases).Etanercept (ETC) was prescribed as the first line of therapy in 10 cases. The most common reason for withdrawal was IE in 5 cases (50% of appointments), AR - 4 cases (40%), AdmR - 1 case (10%). ETC was prescribed as a 2 line in 15 cases, the reasons for withdrawal then were: IE - 11 cases (73.3%), AR - 1 case (6.7%), AdmR - 3 cases (20%). ETC was prescribed as a 3-line therapy in 20 cases. The reasons for withdrawal were as follows: IE - 8 cases (40%), AR - 4 cases (20%), AdmR - 8 cases (40%). As a drug of 4 lines of therapy, ETC was prescribed 1 time and was canceled due to the development of AR. As the 5th line, ETC was appointed in 1 case and was canceled due to IE. ETC was assigned as line 6 in 1 case. The reason for the withdrawal was AR.Adalimumab (ADA) was prescribed as the first line of therapy in 19 cases, the reasons for withdrawal were: IE - 14 cases (73.7%), AR - 2 cases (10.5%), AdmR - 3 (15.8%). On line 2, ADA made 20 appointments, the reasons for withdrawal were: IE - 13 (65%), AR - 3 (15%), AdmR - 4 (20%). ADA was prescribed as line 3 in 8 cases, the reasons for withdrawal were: IE - 6 (75%), AR - 1 (12.5%), AdmR - 1 (12.5%). As a 4-line drug, ADA was prescribed in 4 cases and was canceled in all cases due to IE. On line 5, ADA was assigned 1 time and was discontinuation due to IE.Golimumab (GLM). He was appointed as the first line in 5 cases. The reasons for withdrawal were: IE - 1 case (20%), AdmR - 4 appointments (80%). As a 2-line drug, GLM was prescribed once and was canceled due to AdmR. The drug was not prescribed for the 3rd and 4th lines. As a 5-line therapy, it was prescribed once and was canceled due to IE.When assessing the frequency of drug withdrawal due to IE or AR, no significant differences were found between the lines of therapy. Discontinuation rates were also not statistically different in the study groups.Conclusion:The most common reason for the withdrawal of TNF-α in patients with RRA is IE. With an increase in the lines of TNF-α therapy, remission as a reason for withdrawal was not identified. As a result of the increase in the number of sequentially prescribed bDMARDs, the frequency of discontinuation of TNF-α in connection with IE did not decrease. A significant reason for cancellation is AdmR, to which we attributed the absence of the drug in the pharmacy network, financial reasons limiting the continuation oDisclosure of Interests:None declared

Photodynamic Therapy For Synovial Hyperplasia in Patients With Refractory Rheumatoid Arthritis : A Study Protocol For A Randomised Double-Blind Blank-Controlled Prospective Trial

Background Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is the main cause of refractory rheumatoid arthritis (RRA). As a means of local treatment, photodynamic therapy (PDT) confers less trauma, stronger targeting, and more durable curative effects than steroid injections or arthroscopic synovectomy. The aim of this trial will be to evaluate the short-, medium- and long-term clinical efficacy of PDT in the treatment of RRA synovial hyperplasia and synovitis. Methods and analysis This is a single-centre, randomised, double-blind, blank-controlled, prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the PDT once group, and the PDT twice group, 42 per group. The trial will be conducted at the Rheumatology and Immunology Department of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. Assessments at baseline, the first operation, the second operation (4th week), and then at three follow-ups (8th week, 24th week, 48th week) will be performed. The Ultrasound Compound Score of Synovitis (UCSS), knee joint clinical assessments, Disease Activity Score in 28 Joints (DAS28), serological inflammation indexes and specific antibody levels, pathological biopsies of synovial tissue and X-ray assessments of bone destruction will be evaluated. An improvement in the UCSS will be the main endpoint, and the UCSS at the 8th week versus the baseline value will reflect the short-term outcome of the operation. The results of the 24th week and 48th week follow-up will reflect the medium- and long-term curative effects, respectively. Ethics and dissemination The protocol was approved by the Medical Ethics Committee of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. of the ethics committee: NFZXYEC-2017-005) and later registered in the Chinese Clinical Trials Registry with Registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures will be in accordance with Chinese laws and regulations, as well as the WMA Declaration of Helsinki. Any modifications to the protocol will be approved by the Ethics Committee of our hospital. Trial registration number ChiCTR1800014918.