"I'm so hard!" - Where do patients with rheumatoid arthritis and spinal arthritis in biological treatment severatins go in special periods?

In the current epidemic situation, how can rheumatologists help patients get rid of the worry that "they do not want to relapse due to drug withdrawal, and do not want to increase the risk of cross infection due to frequent hospital treatment"? Novel coronavirus pneumonia is novel coronavirus pneumonia during the epidemic of public health care, which is released by China CDC.however, for rheumatoid arthritis (RA) and spinal arthritis (SPA) patients who need to go to the hospital for biological treatment in the past, this is undoubtedly worse.taking RA as an example, the 2018 guidelines for the diagnosis and treatment of rheumatoid arthritis in China suggests that biological agents should be standardized as far as possible after the start of biological agents treatment, and drug withdrawal or reduction is not allowed at will.after 6 months of treatment, the biological agents can be gradually reduced and the clinical remission state can be maintained for more than 1 year, and the biological agents can be stopped.at present, how can rheumatologists help patients get rid of the worry that "they don't want to relapse because of drug withdrawal, and they don't want to go to the hospital frequently for treatment and increase the risk of cross infection"? Today, I would like to review two classic literatures published in the journal rheumatology, hoping to enlighten you.tumor necrosis factor (TNF) antagonists have become an effective treatment for active RA in recent years.the sustained efficacy of adalimumab, etanercept and infliximab has been demonstrated to significantly improve the symptoms of RA patients, limit the progression of joint damage and subsequent disability [2-4].the therapeutic effects of all three TNF antagonists were inferred from their ability to bind to soluble TNF and block its binding to natural TNF receptors.the combination of TNF antagonist and methotrexate can significantly reduce the clinical disease activity of patients with early or long-term RA, and prevent joint damage [5-8].even if the disease activity is not substantially reduced, TNF antagonists have been shown to reduce joint damage, which indicates that inflammation and joint destruction can be blocked and independently controlled by TNF antagonists [9].these effects are attributed to the role of TNF in synovitis and osteoclast activation and differentiation [9].although TNF antagonists are an important progress in RA treatment, some RA patients may not tolerate these drugs or may not achieve clinically significant treatment response [10].a practical problem faced by clinicians and patients is whether conversion of TNF antagonists can improve clinical response and tolerance.in fact, there are data showing that switching between the three available TNF antagonists (adalimumab, etanercept and infliximab) is safe and effective, and rarely falls off due to intolerance or lack of efficacy after dressing change [11-28].current data suggest that failure to respond to one TNF antagonist does not affect the response to another TNF antagonist, and it may be necessary to test another TNF antagonist before switching to another biological agent.in clinical practice, more data are needed to prove the safety and effectiveness of conversion between TNF antagonists, so as to guide clinicians in the treatment selection after failure of anti TNF treatment.1 in July 2007, S. bombardieri et al. Published the results of a study in rheumatology [29], which aimed to evaluate the clinical efficacy and safety of adalimumab in RA patients who had previously discontinued TNF antagonists for any reason.(Rheumatology, Rheumatology (Oxford). 2007 Jul; 46 (7): 1191-9. EPub 2007 May 15.) react Research (Research in active rheumatoid arthritis) is a large-scale, open label trial, which is the largest study for TNF antagonists in routine clinical practice, to evaluate the safety and efficacy of adalimumab combined with various disease improving antirheumatic drugs (DMARDs) or alone [30].patients with active RA who had been treated with traditional DMARDs or biological agents were enrolled.patients were given adalimumab (40mg, once every other week) for 12 weeks, and they were allowed to enter the optional long-term extended period trial.the ACR response rate, EULAR response rate, 28 joint disease activity score (DAS28) and disability index (HAQ DI) of patients treated with adalimumab were evaluated.in this study, 899 out of 6610 patients were previously treated with etanercept and / or infliximab; these patients achieved substantial clinical benefits after adalimumab treatment.at week 12, 60% of patients achieved ACR20 response, 33% achieved acr50 response, 76% achieved moderate EULAR response and 23% achieved good EULAR response (Figure 1).in addition, 12% of patients achieved DAS28 & lt; 2.6 (indicating clinical remission) and 13% achieved HAQ Di score & lt; 0.5.in terms of the incidence of allergic adverse events, regardless of the relationship with adalimumab, the incidence of patients with previous exposure to TNF antagonists was 6.5/100 patient years, and the incidence rate of patients without previous use of TNF antagonists was 4.3/100 patient years.multiple regression analysis showed that the risk of severe infection was not significantly increased in patients with previous treatment of TNF antagonists compared with those who had not previously used TNF antagonists.Figure 1: the efficacy of adalimumab in the treatment of previously treated patients with TNF antagonists at 12 weeks showed that adalimumab was still effective in 899 patients with moderate to severe RA who had previously failed to receive infliximab, etanercept or both TNF antagonists.there was only a slight difference in the efficacy of adalimumab in patients who had previously used infliximab and etanercept, especially in the ACR response rate (previous medication did not affect the efficacy of adalimumab).over time, more patients who lost initial response to previous TNF antagonists chose to continue adalimumab treatment compared with patients who did not respond or tolerate previous TNF antagonists.adalimumab is generally safe and well tolerated in all patient subgroups; patients who switch from etanercept or infliximab to adalimumab have no additional risk.the safety results of this trial are consistent with the results of previous clinical trials of adalimumab in the treatment of RA.in addition, the results of this open label clinical study indicate that adalimumab is still effective in RA patients who are not responsive or intolerant to other TNF antagonists, and suggest a good risk-benefit ratio in such a population.as observed in the REACT study above, adalimumab remained effective in patients with RA who had previously failed to receive infliximab or etanercept. however, these data can not be directly extrapolated to spa, because the treatment duration rate of conversion to adalimumab after the first use of TNF antagonists in spa patients was not clear at that time, and the relevant data were lacking. 2 after three years, in March 2010, a. Spadaro et al. Published a research result in rheumatology [31], which aims to explore the feasibility of converting adalimumab to adalimumab in spa patients with ineffective infliximab or etanercept treatment or adverse events. (rheumatology 2010; 49:1107 – 1111) this is a retrospective study from nine Italian secondary referral rheumatic centers participating in the spa study. this study collected data on the efficacy and safety of patients with spa who switched from infliximab or etanercept to adalimumab due to ineffective treatment or adverse events between January 2005 and December 2008, and were followed up for at least 6 months. Kaplan Meier survival curve was drawn to compare the drug retention rate between initial treatment (infliximab or etanercept) and adalimumab conversion therapy. in this study, 1619 spa patients were treated with infliximab (35.3%), etanercept (43.7%) and adalimumab (20.9%). among them, 38 patients (2.34%) started treatment with adalimumab as the second TNF antagonist, and 9 patients (0.56%) started treatment with adalimumab as the third TNF antagonist. for whatever reason, the drug retention rate of patients with spa who failed the first anti TNF treatment to switch to adalimumab (second anti TNF treatment) was significantly better than that of the first anti TNF treatment [overall: P & lt; 0.0001 (Fig. 2); infliximab: P & lt; 0.0011 (Fig. 3); etanercept: P & lt; 0.02 (Fig. 4)]. Figure 2 km survival curve of 38 patients with spa: adalimumab treatment (second TNF antagonist) vs infliximab or etanercept (first TNF antagonist) Figure 3 km survival curve of 19 spa patients: adalimumab treatment (second TNF antagonist) vs infliximab (first TNF antagonist) figure 4 Km survival curve of 19 patients with spa: adalimumab treatment (second TNF antagonist) vs etanercept (first TNF antagonist). The results of a real-world retrospective study showed that, regardless of the reason, the switch to adalimumab was effective in patients with spa who did not respond to the first TNF antagonist (such as infliximab or etanercept). this suggests that, regardless of the mechanism of action, switching from one TNF antagonist to another is effective. therefore, adalimumab seems to be a feasible treatment option for patients with spa who have failed to respond to the other two TNF antagonists. in view of the above two research results, it is not difficult to find that patients with RA / spa who have failed to receive biological agents in the past can also obtain ideal efficacy and safety by using another biological agent adalimumab. the 2016 EULAR RA guidelines suggest that for "non-medical reasons", it is not recommended to replace effective biological agents with other biological agents [32]. however, in the current special period of domestic epidemic situation, the delay of treatment due to limited treatment in hospital has become an "irresistible medical factor" that seriously affects the disease control of patients in clinical practice. Therefore, it seems more appropriate to consider the use of biological agents with stable long-term efficacy, good safety and not enough to be injected at home. xiumeile (adalimumab injection) is known as the "king of drugs in the world". It is the first human monoclonal antibody against TNF α in the world. It has been officially included in the national medical insurance drug list in 2019. At present, it has approved five indications for rheumatoid arthritis, ankylosing spondylitis, dandruff disease, polyarthritic juvenile idiopathic arthritis and Crohn's disease in China. in special period, "where is the way?" You can advise your patients to reduce the number of trips to and from the hospital as much as possible. After taking the medicine, the patients can complete the self injection under the professional guidance. in addition, you can also guide patients to inquire about pharmacy information. At present, some pharmacies provide intra city delivery services. in a word, the epidemic affects you and me. I wish the rheumatologists peace of mind and health