Development and verification of a rapid detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line / 中国生物制品学杂志

@#Objective To develop and verify a rapid detection method for the biological activity of adalimumab based on U937-NF-κB-Luc cell line. Methods Using U937-NF-κB-Luc cell line as the detection cells,a method for detecting the biological activity of adalimumab was developed based on luciferase luminescence principle. The method was optimized for the concentration of tumor necrosis factor-α(TNF-α)(160 ng/mL as initial concentration,2 times serial dilution,10dilutions),the initial concentration of antibody(2 000 ng/mL,2 times serial dilution,20 dilutions),the dilution multiple of antibody(1. 5,2,3,4 times),the inoculation amount(8 × 103,2 × 104,4 × 104,6 × 104cells/well)and the incubation time(0. 5,1,2,3 h),and verified for the specificity,accuracy,precision and linear range. The relative potency of five batches of adalimumab was detected by using the optimized method and TNF-α neutralization activity method based on L929cells respectively. Results The dose-response curve of adalimumab international standard showed a typical S-type,and the data complied with the four-parameter equation y =(A-D)/[1 +(x/C)B]+ D,R2> 0. 99. The optimum concentration of TNF-α was 5 ng/mL,the initial concentration of antibody was 800 ng/mL,the dilution ratio for adalimumab was 1∶2,the inoculation amount was 2 × 104cells/well,and the induction time was 2 h. Three therapeutic monoclonal antibodies of TNF-α target,such as adalimumab,obtained good dose-response curves,while therapeutic monoclonal antibodies of other non-TNF-α targets did not show this curve. The linear regression equation of the logarithmic value of theoretical potency and the logarithmic value of the corresponding measured potency had a slope of 1. 037,and the relative bias was within the range of ± 12%. The geometric coefficient of variation(GCV)of the relative titer measured value of each sample was less than20%. The theoretical potency ranged from 64% to 156%,showing a good linear relationship with the measured values,and the fitting linear regression equation was y = 1. 037 4 x-0. 023 7,R2= 0. 998 4. There was no significant difference in the relative potency measured results of five batches of adalimumab by the two methods(t = 1. 198,P = 0. 265 1). Conclusion The developed detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line has good specificity,accuracy and precision with short time consumption(3 h),which can be used as a rapid evaluation method for the biological activity of adalimumab.

Adalimumab combined with Dexamethasone intravitreal implant in the treatment of refractory noninfectious uveitis macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of adalimumab combined with dexamethasone intravitreal implant in the treatment of refractory non-infectious uveitis macular edema(UME).METHODS: A total of 92 cases(131 eyes)of refractory non-infectious UME patients admitted to our hospital from January 2020 to January 2022 were selected and randomly divided into control group, with 46 cases(63 eyes)treated with dexamethasone intravitreal implant and observation group, with 46 cases(68 eyes)treated with adalimumab subcutaneous injection combined with dexamethasone intravitreal implant. The best corrected visual acuity(BCVA), central retinal thickness(CRT), vitreous opacity and Th17/Treg cytokines were measured before and after treatment, and the occurrence of adverse reactions was recorded.RESULTS: Totally 3 cases(4 eyes)were lost to follow-up. After treatment for 1, 3, 6 and 12 mo, BCVA was improved in both groups compared with that before treatment, and CRT, vitreous opacity score, serum interleukin(IL)-17 and IL-22 levels were decreased compared with those before treatment, and serum transforming growth factor-β(TGF-β)and IL-10 levels were increased compared with those before treatment. BCVA in the observation group was better than that in the control group, and CRT, vitreous opacity score, serum IL-17 and IL-22 levels were lower than those in the control group, and serum TGF-β and IL-10 levels were higher than those in the control group(all P<0.05). During treatment and follow-up, no serious adverse reactions occurred in both groups.CONCLUSION: Adalimumab combined with dexamethasone intravitreal implants in the treatment of refractory non-infectious UME can significantly subside the macular edema, reduce vitreous opacity and improve visual acuity.

COVID-19 vaccination, dengue hepatitis, and recurrent unilateral anterior uveitis

A 36-year-old Asian Indian male presented with redness and pain in his right eye of 1 week duration. He was diagnosed to have right acute anterior uveitis and had a history of being admitted at a local hospital for dengue hepatitis a month earlier. He had been on adalimumab 40 mg three weekly once and oral methotrexate 20 mg/week for human leucocyte antigen (HLA) B27 spondyloarthropathy and recurrent anterior uveitis. Our patient had re-activation of his anterior chamber inflammation on three distinct occasions: first, 3 weeks following recovery from coronavirus disease 2019 (COVID-19), the second after the second dose of COVID-19 vaccination, and the third after recovery from dengue fever-associated hepatitis. We propose molecular mimicry and bystander activation as the postulated mechanisms for the re-activation of his anterior uveitis. In conclusion, patients with auto-immune diseases can have recurrent ocular inflammation following COVID-19 or its vaccination or dengue fever as seen in our patient. The anterior uveitis is usually mild and responds to topical steroids. Additional immuno-suppression may not be needed. Mild ocular inflammation following vaccination should not deter individuals from getting COVID-19 vaccination.

The efficacy of anti–TNF-? agents in the treatment of juvenile idiopathic arthritis-associated uveitis in a pediatric cohort

Purpose: Biologic therapy has shown promising control in children with often intractable juvenile idiopathic arthritis (JIA)?associated uveitis (JIA?U). Methods: This is a retrospective cohort study of 35 eyes of 35 children who received biologics for JIA?U. Pretreatment and posttreatment data (at 3, 6, 9, 12, 18, 24, and >24 months) were analyzed to determine functional success (stable/improved visual acuity), quiescence success (?0.5 cells in the anterior chamber), complete steroid success (termination of systemic, periocular therapy and decreased topical drops to ?2/day) or systemic steroid success (termination of systemic steroids only), and complete success (all of the above). Results: This study included 35 eyes up to 12 months and 21 eyes beyond 24 months. Steroid?sparing, functional, and quiescence success showed a rate of success of 52.43%, 77%, and 91%, respectively, at 12 months and 66.67%, 85.7%, and 76.2%, respectively, beyond 24 months. Complete success was 34.29% at 12 months, peaking at 18 months (65.62%) and reached 57.14% beyond 24 months. In their final follow?up, the best corrected visual acuity (BCVA) remained the same in 45.71%, improved in 37.14%, and worsened in 17.14% children. Conclusion: Biologic therapy is effective in JIA?U, especially in termination of systemic steroids, stabilization of vision, and maintaining quiescence

Clinical profile and management with immunosuppressants and biologics in Behcet’s uveitis: A cohort of 25 patients from a tertiary eye care center in South India

Purpose: To report the clinical profile of Behcet’s disease and its management with immunosuppressants and biologics in a cohort of 25 patients from a tertiary eye care center in South India. Methods: This was a retrospective, observational study. Records of 45 eyes of 25 patients between January 2016 and December 2021 were retrieved from the hospital database. Complete ophthalmic evaluation and systemic examination by the rheumatologist with appropriate investigations had been done. Results were analyzed using Statistical Package for the Social Sciences (SPSS) software. Results: Males (19, 76%) were found to be more affected than females (6, 24%). Mean age of presentation was 27.68 ± 11.08 years. Twenty patients had bilateral involvement (80%), and unilateral involvement was seen in five patients (20%). Seven eyes of four patients (16%) had isolated anterior uveitis, out of which one patient had unilateral and three patients had bilateral involvement. Twenty?six eyes of 16 patients (64%) had posterior uveitis, out of which six patients had unilateral and 10 had bilateral involvement. Twelve eyes of seven patients (28%) had panuveitis, out of which two patients had unilateral and five had bilateral involvement. Hypopyon was seen in five eyes (11.1%) and posterior synechiae in seven eyes (15.55%). Posterior segment findings included vitritis (24.44%), vasculitis (17.78%), retinitis (17.78%), disc hyperemia (11.11%), and disc pallor (8.89%). Steroids alone were given in five patients (20%) and intravenous methylprednisolone (IVMP) was given in four patients (16%). Immunosuppressive agents along with steroids were given in 20 patients (80%), of which azathioprine alone was given in seven patients (28%), cyclosporin alone was given in two patients (8%), mycophenolate mofetil alone was given in three patients (12%), combination of azathioprine and cyclosporin was given in six patients (24%), and combination of methotrexate and mycophenolate mofetil was given in one patient (4%). Biologics were given in 10 patients (40%) – adalimumab in seven patients (28%) and infliximab in three patients (12%). Conclusion: Behcet’s disease is an uncommon uveitis in India. Addition of immunosuppressants and biologics to conventional steroid therapy gives better visual outcomes.

Rituximab, a Safer Option for Rheumatoid Arthritis: A Comparison of the Reported Adverse Events of Approved Monoclonal Antibodies

Monoclonal antibodies (mAbs), which are commonly used to treat rheumatoid arthritis (RA), have been linked to a variety of adverse events (AEs). The objective of the study was to compare the safety profiles of six FDA approved mAbs (sarilumab, tocilizumab, adalimumab, golimumab, infliximab, and rituximab) marketed for the treatment of RA. A systematic review of the literature was conducted using the databases PubMed, Cochrane Library, and Science Direct. The manuscript comprised a total of 23 clinical studies. The percentage of patients who had AEs was calculated and presented using box-whisker and forest plots. Infections and infestations were found to be the most common AEs in RA patients treated with mAbs. Raised alanine aminotransferase (ALT), aspartate aminotransferase (AST), upper respiratory tract infection (URTI), and nasopharyngitis were frequently reported. The most common AEs were reported with adalimumab. The highest percentage of patients reporting AEs was associated with golimumab (52%), while rituximab had the fewest AEs (4.9%). In conclusion, rituximab appears to be a safer treatment option for RA as it is found to be associated with a lower risk of AEs, particularly respiratory infections.

Vedolizumabe comparado a agentes anti-TNF-α para indução e manutenção da remissão na doença de Crohn refratária a medicamentos biológicos: revisão rápida / Vedolizumab compared to anti-tnf-α agents for induction and maintenance of remission in biologic-refractory crohn's disease: a rapid review of systematic reviews

Vedolizumabe e anticorpos anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol). Indicação: Tratamento pessoas com doença de Crohn com falha a um agente biológico anti-TNF-α em tratamento prévio. Pergunta: Para adultos com doença de Crohn moderada a grave com falha terapêutica para anticorpos monoclonais anti-TNF-α, em tratamento de segunda linha, Vedolizumabe tem efeitos superiores aos anti-TNF-α para induzir e manter a remissão da doença? Objetivo: Investigar a eficácia e segurança do vedolizumabe, comparado aos agentes anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol), na indução e manutenção da remissão em pacientes refratários aos anti-TNF-α com doença de Crohn moderada a grave. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version) Resultados: Foi selecionada uma revisão sistemática, que atendida aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: Adalimumabe, disponível no Sistema Único de Saúde, é mais eficaz que vedolizumabe para induzir remissão clínica em pacientes tratados previamente com biológicos. Vedolizumabe não é mais eficaz que placebo para induzir remissão clínica. Vedolizumabe e adalimumabe são similares entre si e são mais eficazes que placebo para manter a remissão clínica. Não foram encontradas evidências comparando vedolizumabe a infliximabe ou certolizumabe pegol

Vedolizumab and anti-TNF-α antibodies (infliximab, adalimumab, certolizumab pegol). Indication: Treatment of people with Crohn disease who have failed an anti-TNF-α biological agent in previous treatment. Question: For adults with moderate to severe Crohn disease with treatment failure for anti-TNF-α monoclonal antibodies, in second-line treatment, does vedolizumab have superior effects to anti-TNF-α in inducing and maintaining disease remission? Objective: To investigate the efficacy and safety of vedolizumab, compared to anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), in the induction and maintenance of remission in moderate to severe Crohn disease refractory to anti-TNF-α previous treatment. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library databases and in registries of systematic reviews and clinical trials. The search has followed predefined strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: A systematic review was selected, which met the eligibility criteria, but no clinical trials were chosen as they did not meet the inclusion criteria. Conclusion: Adalimumab, available in the Brazilian Public Health System, is more effective than vedolizumab to induce clinical remission in patients previously treated with biologics. Vedolizumab is no more effective than placebo in inducing clinical remission. Vedolizumab and adalimumab are similar to each other and are more effective than placebo in maintaining clinical remission. No evidence was found comparing vedolizumab to infliximab or certolizumab pegol

Actinomicosis orofaríngea complicada secundaria al tratamiento farmacológico / Complicated oropharyngeal actinomycosis secondary to pharmacotherapy

Anti-tumor necrosis factor (TNF)-α treatment is an effective therapeutic option in intestinal inflammatory chronic disease in cases of the ineffectiveness of other drugs, but it promotes the development of opportunistic infections in their severe forms, due to the profound suppression of T-cell mediated immunity it produces. Among the most frequent are bacterial granulomatous infections, such as mycobacteria (especially tuberculosis), and fungal infections. Actinomycosis is a rare suppurative granulomatous chronic opportunistic infection, which in states of immunosuppression, such as the one caused after treatment with TNF blockers, is complicated by more severe clinical pictures.We present the clinical case, not previously described, of cervicofacial actinomycosis complicated with pneumonia, secondary to treatment with adalimumab in a patient with Crohn's disease.

El tratamiento con anticuerpos anti-factor de necrosis tumoral (TNF) es una opción terapéutica efectiva en la enfermedad inflamatoria crónica intestinal, en casos de ineficacia a otros fármacos, pero favorece la aparición de infecciones oportunistas en sus formas graves, debido a la gran inmunodepresión de células T que produce. Entre las más frecuentes se encuentran las infecciones granulomatosas bacterianas, como las causadas por micobacterias (en la que se destaca la tuberculosis), y las fúngicas. La actinomicosis es una infección oportunista crónica, granulomatosa, supurativa e infrecuente que, en estados de inmunosupresión, como el provocado tras el tratamiento con anticuerpos monoclonales anti-TNF, puede complicarse con cuadros clínicos más graves. Se presenta el caso clínico, no descrito anteriormente, de actinomicosis cervicofacial complicada con neumonía, secundaria al tratamiento con adalimumab, en una paciente con enfermedad de Crohn.

Biotherapy for acne inversa / 中华皮肤科杂志

With the increasing understanding of inflammatory pathogenesis of acne inversa, as well as with the development and application of biological agents in the treatment of autoimmune inflammatory diseases, some biological agents have shown good efficacy and potential for the treatment of acne inversa in clinical research and practice. This review mainly summarizes the research progress in biotherapy of acne inversa in recent years.

Recent advances in efficacy and safety evaluation of adalimumab in non-infectious uveitis / 中华实验眼科杂志

Non-infectious uveitis (NIU) is a serious sight-threatening disease caused by chronic inflammation and its complications.First-line treatment of NIU consists of topical and/or systemic corticosteroids and/or immunosuppressive drugs.Tumor necrosis factor-α inhibitors are recommended in cases of ineffectiveness or intolerance to conventional treatment of NIU.Adalimumab is a fully human monoclonal antibody that is widely used in the treatment of uveitis.Adalimumab is very effective in the treatment of NIU in several prospective and retrospective studies.Adalimumab has also been shown to be safe and effective in the treatment of NIU associated with various systemic diseases in many studies.The application of adalimumab in children, pregnant women, lactating women and other special populations has shown clear efficacy and acceptable side effects.The long-term safety of adalimumab is relatively stable, and no new adverse events have been reported.Compared with other tumor necrosis factor-α inhibitors, adalimumab also has a clear efficacy and better tolerability.This article reviewed the efficacy and safety of adalimumab in the treatment of NIU.

First-line biologic therapy with tumor necrosis factor inhibitors for psoriatic arthritis: a prospective observational study

ABSTRACT BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.

Atualização do custo-efetividade por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe no tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / An update of a cost-effectiveness per response of adalimumab, etanercept, guselcumab, infliximab, ixekizumab, secukinumab and ustekinumab for treatment of moderate to severe plaque psoriasis from the perspective of the Brazilian Supplementary Health System

Objetivo: Os agentes biológicos representam um grande avanço no tratamento da psoríase em placas moderada a grave. No entanto, variações de eficácia, segurança e custos dos tratamentos podem dificultar a escolha do agente terapêutico. Este estudo teve como objetivo atualizar o custo por resposta dos agentes biológicos disponíveis para psoríase no ROL de Procedimentos e Eventos em Saúde (ROL) da Agência Nacional de Saúde Suplementar (ANS). Métodos: Uma análise de custo por resposta foi utilizada para avaliar a razão de custo pelo desfecho Índice de Gravidade e Área da Psoríase (PASI) 90. Os resultados foram apresentados para o primeiro ano (ano I), que compreende a fase de indução e a fase manutenção até completar 52 semanas e foi realizada uma análise da efetividade do tratamento num cenário de orçamento fixo. Os custos dos tratamentos foram calculados com base nos preços de fábrica (PF18%) da Tabela da Câmara de Regulação do Mercado de Medicamentos de junho de 2021. Resultados: Para o ano I, o guselcumabe apresentou melhor resultado para custo por resposta (R$ 130.467) PASI 90, seguido por ixequizumabe, ustequinumabe, secuquinumabe, adalimumabe, infliximabe e etanercepte. No cenário com orçamento fixo, o guselcumabe demonstrou ser o agente capaz de tratar com sucesso (PASI 90) o maior número de pacientes. Atualização do custo-efetividade por resposta para psoríase em placas moderada a grave. Conclusão: Sob a perspectiva do Sistema de Saúde Suplementar do Brasil, o guselcumabe apresentou o melhor custo por resposta PASI 90, sendo, assim, a terapia com melhor custo-efetividade no tratamento da psoríase em placas moderada a grave disponível no ROL.

Objective: Biological agents represent a major advance in the treatment of moderate-to-severe plaque psoriasis. However, variations of efficiency, safety and costs of treatments make it difficult to select the drug. This study aims to update the cost per response of biological agents available in the Health Procedures and Events Roll (ROL) of the National Supplementary Health Agency (ANS). Methods: A cost-per-response analysis was used to assess the cost per outcome of Psoriasis Area and Severity Index (PASI) 90. Results were presented for the first year (I), which comprises induction and maintenance for 52 weeks and a fixed budget scenario analysis. Treatment costs were calculated based on the prices of the 2021 Medicines Market Regulation Chamber Table. Results: Analysis of year I, guselkumab showed the best result for cost per cost (R$ 130,467) PASI 90, followed by ixekizumab, ustekinumab, secukinumab, adalimumab, infliximab, and etanercept. In the fixedbudget analysis, guselkumab is the therapy capable of successfully treating (PASI 90) the largest number of patients. Conclusion: From the perspective of the Supplementary Health System in Brazil, guselkumab showed the best cost per response PASI 90, thus being the most cost-effective therapy in the treatment of moderate to severe plaque psoriasis available in the Brazilian ROL.

Overwhelming response to tumor necrosis factor-? inhibitor infliximab “innovator” versus adalimumab “bio-similar” in a previously therapy naive adult: A case report

Therapeutic options for the patient with spondyloarthritis (SpA) are limited. The pharmacotherapy for SpA comprises immunomodulator/suppressive drugs. In this case report, we describe the case of a 29-year-old postgraduate resident in medicine who was diagnosed with SpA and was managed by a combination of various disease-modifying drugs such as methotrexate and sulfasalazine, and immunomodulators such as systemic corticosteroids and tumor necrosis factor (TNF)-? inhibitors. After a series of therapeutic trials with them, the chimeric TNF blocker infliximab led to significant clinical improvement in symptoms and reduction in disease activity

Efficacy and safety of adalimumab in the treatment of Crohn′s disease / 中华消化杂志

Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.

The efficacy of adalimumab for the treatment of refractory active Takayasu arteritis / 中华风湿病学杂志

Objective:To explore the efficacy and safety of adalimumab (ADA) in Chinese Takayasu arteritis (TAK) patients.Methods:This study prospectively included ten refractory active TAK patients. The clinical, laboratory and imaging data of these patients before and after ADA treatment were collected and compared. Statistical analysis was carried out with the statistical product and service solutions (SPSS) program V.24.0. We performed univariate analysis by Wilcoxon-Mann-Whitney test for numerical data according to normality. The P value <0.05 was interpreted as statistically significant. Results:Ten TAK patients recruited in this study were all female, with a median age of 27.5 [25.0, 36.0] years. Fever or fatigue (6/10, 60%), neck pain (6/10, 60%), and limb claudication (4/10, 40%) were the most common clinical manifestations. The most common pattern of vascular involvement was Numano type V (7/10, 70%). The serum erythrocyte sedimentation rate (ESR) [22.0(4.5, 37.5) mm/1 h vs 7.0(4.5, 31.0) mm/1 h, Z=-2.04, P=0.042] and IL-6 level [12.3(3.6, 57.7) ng/L vs 2.8(2.0, 24.0) ng/L, Z=-2.19, P=0.028] reduced significantly after ADA treatment. The thickness of the common carotid artery intima decreased from 2.7(2.2, 4.0) mm to 2.3(1.6, 3.4) mm after ADA treatment ( Z=-1.99, P=0.046). The lumen diameter of the common carotid artery increased from 0.31(0.20, 0.42) cm to 0.37(0.29, 0.43) cm ( Z=-2.02, P=0.043). The glucocorticoid dosage was reduced from [11.2(6.9, 15.0) mg to 10.0(5.0, 13.1) mg, Z=-1.89, P=0.059]. In the 10 patients, 6 patients (60%) reached complete response, 2 patients (20%) reached the partial response, and the total effective rate was 80%(8/10). Pneumonia in one TAK patient was recorded. Conclusion:The results of this study suggest, that ADA can be used for refractory active TAK patients, and is safe.

Study on the effect of functional movement on the recurrence of patients with ankylosing spondylitis after treat-to-target therapy / 中华风湿病学杂志

Objective:To investigate the effect of functional movement assessment on the recurrence of patients with ankylosing spondylitis (AS) after treat-to-target therapy.Methods:The clinical data of 61 patients with AS in Chengdu were collected including clinical symptoms and AS disease activity (ASDAS). After 24 weeks adalimumab treatment, motor function score of AS patients(ASDAS<1.3) was assessed by functional movement screen (FMS), then adalimumab was discontinued and the rest of the concurrent drugs were continued until the disease relapse or up to 1 year. The data of the two groups were compared using t-test analysis and Cox proportionate hazard model. Results:① The recurrence rate of patients with AS after treat-to-target therapy within 1 year follow-up was 57.4%; ② The recurrence group was younger [(27±7) vs (31±6), t=5.96, P=0.02], the ASADAS value was at the high end when adalimumab was withdrawal [(1.29±0.07) vs (0.87±0.16), t=177.31, P<0.01], and the FMS value was lower after treat-to-target [(12.9±2.7) vs (16.2±1.9), t=29.23, P<0.01], The time to reaching the treatment target was longer [(2.9±1.2) month vs (1.7±0.6) month, t=19.89, P<0.01] than the stable group; ③ The cut-off value of the FMS test of AS patients after treat-to-target therapy was 14.25 (sensitivity was 84.6%, specificity was 80%) . The time to treat-to-target was a risk factor for recurrence ( RR=2.285, P<0.05), and the FMS value after treat-to-target was a protective factor ( RR=0.625, P<0.05). Conclusion:After discontinuing the adalimumab, about half of the patients relapse. The time reaching the treatment target and the FMS value after treat-to-target therapy are the risk factors for disease recurrence.

Influence of function movement on the outcome of ankylosing spondylitis under the treat-to-target stratery / 中华风湿病学杂志

Objective:To investigate the effect of baseline function movement assessment of ankylosing spondylitis (AS) on treatment outcomes.Methods:The clinical data of 90 patients with AS who met the medical insurance treatment for major disease in Chengdu were collected including clinical symptoms, functional movement screen (FMS) and ankylosing spondylitis disease activity score (ASDAS) after 24 weeks adalimumab treatment. They were divided into the non-treat-to-target group and the non-treat-to target group based on the ASDAS score, t-test or χ2 test was used to compare the differences between the two groups. Logistic regression model was used to analyze the influence of baseline FMS on the outcome of patients reaching the treatment target. Results:① The two groups were different in the FMS [(15.8±2.3) vs (12. 6±2.5), t=6.17, P<0.001], squat [(2.2±0.6) vs (1.7±0.5), t=3.57, P=0.001], hurdle spanning [(2.2±0.7) vs (1.8±0.6), t=2.11, P=0.038], straight lunge [(2.3±0.7) vs (1.7±0.5), t=4.23, P<0.001], shoulder flexibility [(2.5±0.6) vs (2.2±0.8), t=2.21, P=0.037], active straight leg raise [(2.1±0.6) vs (1.8±0.6), t=2.35, P=0.021], spinal stabilization pushups [(2.4±0.7) vs (1.8±0.8), t=3.76, P<0.001], body rotation stability [(2.2±0.7) vs (1.6±0.8), t=3.42, P=0.001] at baseline. ② The two groups were different in ASDAS score [(0.96±0.28) vs (2.19±0.52), t=14.69, P=0.000], FMS [(17.4±1.9) vs (12.7±2.8), t=9.77, P<0.001], deep squat [(2.6±0.5) vs (1.5±0.5), t=9.09, P<0.001], hurdle step [(2.2±0.6) vs (1.8±0.8), t=2.80, P=0.006], straight lunge [(2.6±0.6) vs (1.8±0.9), t=4.85, P<0.001], shoulder flexibility [(2.8±0.4) vs (2.5±0.5), t=2.10, P=0.038], active straight leg raise [(2.2±0.6) vs (1.9±0.8), t=2.46, P=0.016], spinal stability push-ups [(2.8±0.4) vs (1.6±0.7), t=10.36, P<0.001], and body rotation stability [(2.3±0.7) vs (1.6±0.8), t=4.76, P<0.001] at the end of the observation. ③ The cut-off value of the FMS for predicting whether AS patients meet the standard at baseline was 14.25 points (Sensitivity 0.733, specificity 0.800). ④ Logistic regression results showed that in the baseline, FMS series of action tests, squat [ OR (95% CI)=0.155 (0.035, 0.677), P=0.013], straight lunge [ OR (95% CI)=0.375 (0.148, 0.953), P=0.039], spinal stability push-ups [ OR(95% CI)=0.136(0.043, 0.436), P=0.001], and body rotation stability [ OR(95% CI)=0.308 (0.121, 0.780), P=0.013] were the influencing factors of the AS patient's treatment outcome ( P<0.05). Conclusion:The AS patients in the non-treat-to-target group have better FMS tests at baseline and at the end of the study than the non-treat-to-target group. Squats, straight lunges, remember stable push-ups, and body rotation stability are the influencing factors for the treatment outcomes of AS patients at baseline.

Efficacy and safety of Adalimumab in treating pediatric Crohn′s disease / 中华实用儿科临床杂志

Objective:To evaluate the efficacy and safety of Adalimumab(ADA) in the treatment of pediatric Crohn′s disease (CD).Methods:The clinical data of 20 CD patients treated with ADA at Beijing Children′s Hospital, Capital Medical University from September 2016 to September 2021 were retrospectively analyzed.The disease activity status and mucosal inflammation in CD patients were evaluated using the Pediatric Crohn′s Disease Activity Index (PCDAI) and Crohn′s Disease Endoscopic Severity Index(CDEIS). Data were compared between groups using the rank sum test or Fisher′ s exact test. Results:A total of 20 CD patients were recruited, including 12 males and 8 females.The mean age at diagnosis of CD was (9.5 ± 4.9) years old, ranging from 0.9-15.1 years old.The mean age of the first use of ADA was (10.4 ± 4.8) years old, ranging from 1.2-16.7 years old.The median duration of CD symptoms before ADA treatment was 0.9 (0.4, 1.7) years.The mean PCDAI score of 20 CD patients before ADA treatment was (28.5±19.8) points (range: 0-65.0 points). Of the 20 cases, 8 cases (40.0%) had severe disease activity, and 4 cases (20.0%) were in remission.A total of 15 CD patients underwent CDEIS assessment.The results showed that 9 patients had moderate to severe disease activity, and the symptoms were improved in 1 case under endoscopy.Ten patients (10/20 cases, 50.0%) received Infliximab (IFX) treatment preceding ADA treatment.IFX discontinuation was due to the loss of response(8/10 cases, 80.0%) and allergic reactions (2/10 patients, 20.0%). After 6 weeks of ADA treatment, the median PCDAI score of the 20 CD patients was 5.0 (0, 10.0) points, which was significantly lower than that before ADA treatment ( P<0.001). The clinical remission rate and clinical response rate of 16 patients with active CD treated with ADA for 6 weeks were 62.5% (10/16 cases) and 87.5% (14/16 cases), respectively.There were no significant differences in the clinical remission rate and clinical response rate between the patients who did not receive IFX and those who had previously received IFX(all P> 0.05). The median ADA treatment period was 5.5 (2.6, 17.8) months.During the follow-up period, 6 patients (6/20 cases, 30.0%) suffered from clinical recurrence of CD.At the end of the follow-up visit, seventeen patients(17/20 cases, 85.0%) maintained clinical remission, one had primary non-response and two experienced secondary non-response.Adverse events were reported in 7 patients, mainly including pneumonia (4 cases) or upper respiratory tract infection (2 cases). No tumor or other serious adverse events were recorded. Conclusions:ADA has good efficacy in inducing and maintaining clinical remission in pediatric CD patients, and does not cause serious adverse events.

Risk signal mining of adverse event related to adalimumab based on FAERS / 中国药房

OBJECTIVE To provide reference for clinical safe and rational use of adalimumab by mining the risk signals of adverse event （AE）. METHODS AE reports related to adalimumab were collected from FDA adverse event reporting system （FAERS）from Jan. 1st，2015 to Dec. 31th，2021. The reporting odds ratio （ROR）method and the Medicines and Healthcare Products Regulatory Agency （MHRA） method were adopted to mine the AE risk signals related to adalimumab ，AEs were classified and described by using the preferred system organ class （SOC）and preferred term （PT）of Medical Dictionary for Regulatory Activities （23.0）. RESULTS A total of 149 203 AE reports related to adalimumab were screened ，among which 65 218 cases（43.71％）were severe AE reports. A total of 2 660 PTs were mined ，involving 27 SOCs. PTs related to primary disease （arthralgia，Crohn’s disease ，rheumatoid arthritis ，abdominal pain ，osteoarthritis，intestinal obstruction ，psoriasis，joint swelling ， arthritis，etc.）were more frequently reported ，followed by PTs related to inflammation and pain （procedural pain ，inflammation， etc.）. The main SOC included musculoskeletal and connective tissue diseases （68 227 cases），gastrointestinal diseases （50 682 cases），injury，poisoning and procedural complications （32 404 cases），infections and infestations （15 651 cases），general disorders and administration site conditions （15 424 cases），etc. CONCLUSIONS It is suggested to pay attention to the possible occurrence of paradoxical psoriasis and lupus-like syndrome related to the autoimmune system when using adalimumab clinically ； at the same time ，the attention should be paid to serious infection ，tuberculosis，malignant tumors ，demyelination，congestive heart failure and other AEs. If related AEs occurs ，intervention measures should be taken in time. Great importance should be paid to intracranial aneurysms ，ovarian cysts ，coronary artery occlusion ，thyroid masses and other AEs not mentioned in the instrcution ，to ensure the medication safety of patients.

Adalimumab combined with acitretin in the treatment of five children with generalized pustular psoriasis: a retrospective clinical observation / 中华皮肤科杂志

Objective:To evaluate the clinical efficacy and safety of adalimumab combined with acitretin in the treatment of childhood generalized pustular psoriasis.Methods:Five children with generalized pustular psoriasis were collected from Department of Dermatology, Tianjin Children′s Hospital from October 2019 to August 2020. After admission, the patients received oral acitretin at a dose of 0.5 mg·kg -1·d -1. After relevant laboratory examinations, these patients additionally received subcutaneous injections of 20- or 40-mg adalimumab at weeks 0 (the initial dose) , 1, and every 2 weeks thereafter; when patients obtained a 50% improvement in the Japanese Dermatology Association (JDA) severity index score, the dose of acitretin would be reduced to 0.3 mg·kg -1·d -1, and acitretin would be discontinued after a 75% improvement. The disease condition was evaluated at weeks 0, 1, 2, 4, 8, 12 and 24 after the start of adalimumab treatment, and adverse reactions were monitored during treatment. Results:All the 5 patients received drug treatment for at least 40 weeks. After 2-week treatment, 3 patients achieved a 50% reduction in JDA severity index score (JDA50) ; after 4-week treatment, 4 achieved JDA75, and 1 achieved JDA100; after 8-week treatment, all the 5 patients achieved JDA100. By June 2021, all the 5 children received follow-up for at least 40 weeks, no recurrence was observed during the treatment period, and no infections, malignant tumors or other serious adverse reactions occurred.Conclusion:Adalimumab combined with acitretin shows rapid onset of action and high safety in the treatment of childhood generalized pustular psoriasis.