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OBJECTIVES: To investigate unacceptable pain (UP; visual analogue scale [VAS] >40 mm) and uncontrolled inflammation (C-reactive protein [CRP] ≥1.0 mg/dL) in patients with active rheumatoid arthritis (RA) receiving sarilumab (SAR) as monotherapy or in combination with non-methotrexate conventional synthetic disease-modifying antirheumatic drugs (SAR+csDMARDs). METHODS: In the HARUKA phase 3 study (NCT02373202), Japanese patients received either SAR monotherapy (n=61) or SAR+csDMARDs (n=30). In this post-hoc analysis, changes in the proportions of patients with/without UP and controlled/uncontrolled inflammation were assessed over 52 weeks. RESULTS: At baseline, 80.3% (49/61) of patients receiving SAR monotherapy had UP and this proportion decreased with treatment to 55.9% (33/59) at Week 4 and 15.5% (9/58) at Week 52. The SAR+csDMARDs group achieved a reduction in UP from 73.3% (22/30) at baseline to 34.5% (10/29) at Week 4 and 0% (0/24) by Week 52. At baseline, 34.4% (21/61) and 50% (15/30) of patients had both UP and uncontrolled inflammation in the SAR monotherapy and SAR+csDMARDs groups; by Week 2, the proportions decreased to 6.6% (4/61) and 3.3% (1/30), respectively; and 0% in both groups by Week 52. CONCLUSION: UP and inflammation were reduced in patients with active RA in Japan in both SAR monotherapy and SAR+csDMARDs treatment groups.
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OBJECTIVES: This study aimed to assess the efficacy and safety of sarilumab in older patients with active rheumatoid arthritis (RA). METHODS: This is a post-hoc analysis of KAKEHASI (NCT02293902) and HARUKA (NCT02373202) trials with stratification by age (<65 and ≥65 years). Patients with moderately-to-severely active RA were treated with sarilumab in combination with methotrexate (MTX) or with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy. The primary endpoints in KAKEHASI and HARUKA trials were the American College of Rheumatology 20% improvement criteria (ACR20) responses at Week 24 and safety, respectively. Secondary endpoints were other RA disease activity measures, including Clinical Disease Activity Index (CDAI). RESULTS: Approximately 20% of patients were aged ≥65 years in treatment arms across both trials, except the sarilumab+csDMARDs arm (40%, 12/30). ACR20 response rates were similar between age groups across sarilumab treatment arms and similar results were obtained for CDAI scores. Safety profiles were similar between age groups except for a higher incidence of serious adverse events in patients aged ≥65 years in the sarilumab+MTX arm. CONCLUSIONS: In Japanese patients with RA enrolled in phase 3 studies for sarilumab, no clear difference in efficacy or safety was observed between patients aged <65 and ≥65 years.
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OBJECTIVES: Using data from a post-marketing surveillance, this interim subgroup analysis investigated the safety of sarilumab in younger (<65 years) and older patients (≥65 and ≥75 years) with rheumatoid arthritis. METHODS: During this interim analysis, patients who were treated with sarilumab in Japan were enrolled between June 2018-2021. Data collected by 12 January 2022 were analysed, with adverse drug events monitored over 52 weeks. RESULTS: Of 972 patients with available data, proportion of patients aged <65 years, ≥65 years and ≥75 years were 40.8%, 59.2% and 27.8%, respectively. Most patients (95.5%) received the standard 200 mg dose of sarilumab as the initial dose. Adverse drug reactions were reported in 24.6% of patients, with serious events accounting for 6.4% of cases. No malignancy and low incidences of adverse drug reactions of special interest were reported across all age groups (<65 years, 7.8%; ≥65 years, 8.2%; ≥75 years, 8.5%). When stratified by absolute neutrophil count above and below the lower limit of normal, there were no numerical differences in incidences of serious and non-serious infections between age groups. CONCLUSIONS: Regardless of age, sarilumab therapy was well tolerated by patients with rheumatoid arthritis, with no new safety signals reported in this study.
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OBJECTIVES: To report up to 3-year safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a postmarketing surveillance study. METHODS: Patients enrolled previously completed 24 weeks of CZP in the 24-week postmarketing surveillance study. Adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes were 28-joint Disease Activity Score with erythrocyte sedimentation rate and European Alliance of Associations for Rheumatology response. Week 24-156 safety and Week 0-52 effectiveness data are reported here. RESULTS: A total of 781 patients were enrolled, with 735 and 376 patients evaluated for safety and effectiveness, respectively. Within the safety set, 17.8% (131/735) of patients reported ADRs; 9.4% (69/735) reported serious ADRs. Among patients with history of respiratory, thoracic, and mediastinal disorders, 38.4% (28/73) reported ADRs. The most frequent ADRs were infections and infestations (11.8%; 87/735); skin and subcutaneous tissue disorders (1.9%; 14/735); respiratory, thoracic, and mediastinal disorders (1.6%; 12/735). Mean 28-joint Disease Activity Score with erythrocyte sedimentation rate reduced from 4.6 (Week 0) to 2.8 (Week 52). At Week 52, 51.8% (161/311) of patients achieved European Alliance of Associations for Rheumatology Good response. CONCLUSIONS: The long-term safety and effectiveness of CZP in the real-world setting in Japan were consistent with previously reported data; no new safety signals were identified.
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OBJECTIVES: A quality indicator for the treatment of systemic lupus erythematosus during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a quality indicator for systemic lupus erythematosus associated with pregnancy and childbirth. METHODS: To identify candidate quality indicators, we conducted a systematic literature review on the development of quality indicators for systemic lupus erythematosus related to pregnancy and childbirth and on clinical practice guidelines. Candidate quality indicator items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as quality indicators. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related systemic lupus erythematosus quality indicators. RESULTS: Four articles on systemic lupus erythematosus-quality indicator development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate quality indicators were extracted that were limited to items related to pregnancy and childbirth, and 41 items were selected on which all panel members agreed. CONCLUSION: We developed pregnancy-related systemic lupus erythematosus quality indicators using the RAND/UCLA method and selected 41 items, which could be used clinically.
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OBJECTIVES: An interim analysis of post-marketing surveillance data to assess the safety and effectiveness of sarilumab in Japanese patients with rheumatoid arthritis refractory to previous treatment. METHODS: The interim analysis included patients who initiated sarilumab therapy between June 2018 and January 2021. The primary objective of this surveillance was safety. RESULTS: In total, 1036 patients were enrolled and registered by 12 January 2021 (interim cut-off date). Of these, 678 were included in the safety analysis [75.4% female; mean age (± standard deviation) 65.8 ± 13.0 years]. Adverse drug reactions, defined as adverse events classified as possibly or probably related to sarilumab, were reported in 170 patients (incidence: 25.1%), with white blood cell count decreased (4.4%) and neutrophil count decreased (1.6%) most frequently reported. Serious haematologic disorders (3.4%) and serious infections (including tuberculosis) (2.5%) were the most frequently reported priority surveillance items. No malignant tumour was reported. An absolute neutrophil count (ANC) below the minimum standard value did not increase the incidence of serious infections. CONCLUSIONS: Sarilumab was well tolerated, and no new safety signals were noted in this analysis. There was no difference in the frequency of serious infections between patients with an ANC below or above normal.
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Anticuerpos Monoclonales Humanizados , Antirreumáticos , Artritis Reumatoide , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Antirreumáticos/efectos adversos , Japón , Resultado del Tratamiento , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Vigilancia de Productos ComercializadosRESUMEN
Patients with psoriatic arthritis (PsA) often experience comorbid, irreversible joint destruction, therefore early diagnosis and treatment of PsA are important. The diagnosis requires a comprehensive assessment, which includes an interview, a physical examination, a visual examination of the skin and nails, a blood test, and an imaging test. To clarify how patients with PsA are actually diagnosed and how physicians collaborate among clinical departments, we conducted a web-based questionnaire survey of 500 physicians (dermatologists, rheumatologists, and orthopedists) frequently involved in PsA treatment in Japan. The survey showed that those patients are rarely confirmed to have axial arthritis, peripheral arthritis, enthesitis, or dactylitis by general dermatology practitioners (GP dermatologists). Overall, <60% of patients suspected of having PsA underwent PsA examination by GP dermatologists more than once every 6 months; this percentage is lower than that of patients who underwent PsA examination by rheumatologists and orthopedists. The Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire is the most commonly used for PsA screening. However, users of PASE were only 11.0%, 25.3%, 14.8%, and 24.1% of GP dermatologists, attending dermatologists in hospitals (HP dermatologists), rheumatologists, and orthopedists, respectively. While >80% of HP dermatologists, rheumatologists, and orthopedists used imaging tests (ultrasound, X-ray, and magnetic resonance imaging) for PsA screening, only 40% of GP dermatologists performed imaging tests. Regarding the demands on the healthcare environment of PsA treatment, early diagnosis and treatment for PsA are crucial in every clinical department. The present study showed that GP dermatologists rarely perform imaging tests or confirm a PsA diagnosis, thus patients may miss out on appropriate treatment through collaboration among clinical departments and step-up therapy. Because patients with PsA present diverse comorbid clinical symptoms, early diagnosis, including routine imaging tests, and appropriate treatment in collaboration with other experts are necessary.
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Artritis Psoriásica , Médicos , Psoriasis , Humanos , Artritis Psoriásica/terapia , Artritis Psoriásica/tratamiento farmacológico , Estudios Transversales , Japón , Tamizaje Masivo , Psoriasis/diagnósticoRESUMEN
Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for the treatment of RA in Japan in 1999 at a recommended dose of 6-8 mg/week. The approved maximum dose of MTX has been 16 mg/week since February 2011 when MTX was approved as a first-line drug in the treatment of RA. Recent evidence of MTX-polyglutamate concentration in the red blood cells of Japanese patients with RA justifies the current daily use of MTX in Japan. Additionally, after a nationwide clinical trial, a subcutaneous MTX injection formula (7.5-15 mg/week) was approved for RA treatment in September 2022. Therefore, in March 2023, a subcommittee of the Japan College of Rheumatology updated the guidance (formerly 'guidelines') for the use of MTX in Japanese patients with RA. This article, an abridged English translation summarizing the 2023 update of the Japan College of Rheumatology guidance for the use of MTX and management of patients with RA, will be helpful to both Japanese and global rheumatology communities.
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Antirreumáticos , Artritis Reumatoide , Reumatología , Humanos , Metotrexato , Japón , Antirreumáticos/efectos adversos , Resultado del Tratamiento , Artritis Reumatoide/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
INTRODUCTION: The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial. METHODS: Patients were treated with placebo, ixekizumab 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), or adalimumab 40 mg Q2W for 24 weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression. RESULTS: In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified. CONCLUSIONS: In patients with severe psoriatic arthritis, 24 weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01695239.
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BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study. METHODS: Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported. RESULTS: Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population. CONCLUSIONS: Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure. TRIAL REGISTRATION: NCT02049138.
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Antirreumáticos , Espondiloartritis , Espondilitis Anquilosante , Humanos , Antirreumáticos/efectos adversos , Terapia Biológica , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Espondilitis Anquilosante/tratamiento farmacológico , Inhibidores del Factor de Necrosis TumoralRESUMEN
A 20-year-old woman with bilateral common carotid artery stenosis was diagnosed with Takayasu arteritis (TA). She suffered from a recurrent stroke, and repeated transient ischemic attacks (TIAs) occurred due to middle cerebral artery (MCA) stenosis. The clinical course indicated that TA contributed to MCA stenosis despite the negative results for serological inflammation markers. Immunotherapy with tocilizumab and methotrexate effectively reduced disease activity and improved symptoms. Bed rest and hydration prevented further TIAs and ischemic stroke progression. Long-term monitoring of neurological symptoms and angiography findings is essential to evaluate disease severity and treatment efficacy in TA patients with negative inflammatory markers.
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AIM: Intravenous tocilizumab (TCZ-IV) was approved for the treatment of adult Still's disease (ASD) in Japan in May 2019 based on its efficacy and safety in a phase III randomized controlled trial. This study determined treatment patterns in patients with ASD and assessed oral glucocorticoid (GC) dose changes after TCZ-IV administration in Japanese clinical practice. METHODS: Patients in the Medical Data Vision database aged 16 years or older with one or more of International Classification of Diseases, 10th revision codes M061 (ASD) or M082 (systemic juvenile idiopathic arthritis) during January 2017-March 2021 (cohort 1) and those initiating TCZ-IV during May 2019-March 2021 (cohort 2) were included. RESULTS: In cohort 1, the proportion of patients who were prescribed interleukin-6 inhibitors (mainly TCZ-IV) increased from 10.8% (January-April 2019 [before TCZ-IV approval]; n = 2002) to 18.3% (January-March 2021 [after TCZ-IV approval]; n = 2008). In cohort 2 (n = 193), 84.5% of patients were on oral GCs (≤5 mg/day: 23.8%) at index date (initial TCZ-IV prescription date); 46/70 (65.7%) were on oral GC at 5 mg/day or higher 12 months after TCZ-IV treatment (primary outcome). After 12 months of treatment, the TCZ-IV retention rate was 73.6% and the TCZ-IV administration interval was every 4 weeks and every 2 weeks in 31.9% and 27.7% of patients, respectively. CONCLUSION: The use of interleukin-6 inhibitors increased by 7.5% points in Japanese patients with ASD ~2 years after TCZ-IV approval, suggesting that an unmet medical need existed. This study suggests the potential GC-sparing effect of TCZ-IV in patients with ASD in clinical practice.
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This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)-4 and IL-13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL-31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti-IL-4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti-IL-31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti-IL-13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board-certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients.
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Productos Biológicos , Dermatitis Atópica , Humanos , Productos Biológicos/uso terapéutico , Citocinas , Dermatitis Atópica/tratamiento farmacológico , Interleucina-13/uso terapéutico , Prurito/etiología , JapónRESUMEN
OBJECTIVE: The aim of this study is to investigate the effects of sarilumab on unacceptable pain [UP; visual analogue scale (VAS) >40 mm] and inflammation in patients with moderately-to-severely active rheumatoid arthritis. METHODS: In this post hoc analysis of the KAKEHASI study, 243 patients received methotrexate with sarilumab 150 or 200 mg or placebo every other week, over 52 weeks. The proportion of patients with UP and correlations of changes in pain VAS from baseline with uncontrolled inflammation (C-reactive protein ≥1 mg/dl) and disease activity indices were assessed. RESULTS: Almost 80% of patients (192/243) had UP at baseline, including â¼60% of patients with uncontrolled inflammation. Among patients receiving sarilumab, inflammation decreased rapidly, with 90% of patients achieving controlled inflammation by Week 2, while 63.1% continued to have UP. The proportion of patients with UP further decreased by Week 16 (28.5%, sarilumab vs. 64.0%, placebo). By Week 52, only â¼10% of patients had UP. Changes in pain VAS correlated with most disease activity indices and patient-reported outcomes. However, marked correlations between changes in pain VAS and C-reactive protein were observed only at Week 16. CONCLUSION: Sarilumab treatment reduced UP and inflammation in Japanese patients with rheumatoid arthritis.
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BACKGROUND: This study aimed to provide an overview of ultrasonographic cartilage evaluation in patients with rheumatoid arthritis (RA) and identify research gaps in the utilization of cartilage evaluation. METHODS: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. A systematic literature search of the PubMed, Embase, and Cochrane Library databases was conducted for articles published up to July 2022 using the search term variations of "cartilage," "ultrasonography," and "rheumatoid arthritis." Studies that included patients with RA who underwent cartilage evaluation by ultrasonography were selected. Articles published in languages other than English and about juvenile idiopathic arthritis were excluded. RESULTS: Twenty-nine articles were identified. Most were cross-sectional studies (86%), mainly involving the metacarpophalangeal (55%) and knee (34%) joints. Assessments were performed using quantitative, binary, and semi-quantitative methods in 15, 10, and 15 studies, respectively. Reliability assessments were conducted in 10 studies, which showed feasible reliability but were limited to the finger joints. The validity assessment was validated in one study each that compared cartilage thickness measurements with cadaveric specimens and histological and semi-quantitative methods with surgical specimens, respectively. Comparisons with conventional radiography were also performed in six studies, which showed significant correlations. However, there was heterogeneity in the examination and assessment methods, and no adequate longitudinal evaluation was conducted. CONCLUSION: This review highlights the need for further research and validation of ultrasonographic cartilage assessment in patients with RA.
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OBJECTIVE: To investigate sustained remission following the discontinuation of tofacitinib in patients with rheumatoid arthritis. METHODS: Patients who had an inadequate response to methotrexate (MTX) with or without biological disease-modifying antirheumatic drugs were randomly divided into two groups at baseline, and tofacitinib treatment in combination with MTX was administered to both groups. Either MTX or tofacitinib was then withdrawn if patients achieved Clinical Disease Activity Index remission at week 52. The primary outcome was the proportion of patients who sustained clinical remission at week 104. RESULTS: A total of 113 patients participated in this study. Among them, a total of 48 patients achieved remission at week 52. After discontinuation of tofacitinib, only 29.2% (7/24) of patients remained remission, while 50.0% (10/20) of patients, which was numerically higher but not statistically significant, sustained remission after MTX discontinuation. A greater proportion of bio-naïve patients achieved remission at week 52 and sustained low disease activity with tofacitinib discontinuation at week 104. Additionally, the patients who were able to discontinue tofacitinib without flares had lower rheumatoid factor (p=0.04) and lower anti-cyclic citrullinated peptide antibody (p=0.051) before discontinuation of tofacitinib. No severe adverse events were recorded after discontinuation of tofacitinib or MTX. In patients who relapsed after tofacitinib discontinuation, 71.4% achieved remission with resumption of tofacitinib. CONCLUSIONS: This study implies that a blanket cessation of tofacitinib may not be suitable for all patients, given that 58% of the participants experienced relapse. However, the withdrawal of tofacitinib is unlikely to result in the acquisition of treatment-resistance.
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Antirreumáticos , Artritis Reumatoide , Humanos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Antirreumáticos/efectos adversos , Metotrexato/efectos adversos , Piperidinas/efectos adversosRESUMEN
BACKGROUND: Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here. METHODS: In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0-8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0-72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0-24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0-69). RESULTS: Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, - 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], - 1.23 [2.81] vs - 0.37 [1.90] with placebo) was sustained through week 104 (- 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104). CONCLUSION: Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02696031.
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Espondiloartritis Axial no Radiográfica , Sacroileítis , Espondiloartritis , Espondilitis Anquilosante , Adulto , Humanos , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/patología , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/patología , Articulación Sacroiliaca/diagnóstico por imagen , Articulación Sacroiliaca/patología , Imagen por Resonancia Magnética/métodos , Inflamación/patología , Sacroileítis/patologíaRESUMEN
Among various tyrosine kinases, a family of Janus kinases (JAK) has been elucidated as key players in signal transduction from vital cytokine receptors, such as interleukins and interferons. Indeed, recent rapid progress in JAK inhibitors in addition to biological agents provided therapeutic options for various diseases, including immune-mediated inflammatory diseases and hematological disorders. Efforts have culminated in the approval of nine JAK inhibitors in Japan in the recent decade. The safety profiles of JAK inhibitors seem to largely depend on patient populations and drug dosing, rather than on JAK selectivity. Thus, the comparison of various disease indications is pivotal for the understanding and proper use of JAK inhibitors.