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OBJECTIVE: To compare health-related quality of life (HRQoL) and work productivity in axial spondyloarthritis (axSpA) and non-axSpA patients with chronic back pain of < 2 years (2 y). METHODS: Baseline and 2 y data of patients included in the SPondyloArthritis Caught Early cohort were analyzed. HRQoL was assessed by the physical (PCS) and mental component summary (MCS) scores of the 36-Item Short-Form Health Survey; and presenteeism, absenteeism, work productivity loss (WPL) and activity impairment (AI) by the Work Productivity and Activity Impairment questionnaire. Linear or zero-inflated negative binomial regression was conducted to compare 2 y outcomes between groups (axSpA and non-axSpA), adjusting for the baseline value, sex, age and use of nonsteroidal anti-inflammatory drugs. RESULTS: There were 265 axSpA and 108 non-axSpA patients: males 52% vs 26%, mean age 29 vs 31 years, respectively. At baseline, non-axSpA patients showed worse PCS (mean 28.6 axSpA vs 26.6 non-axSpA), presenteeism (31.1% vs 37.3%), absenteeism (8.2% vs 10.3%), WPL (34.7% vs 44.1%) and AI (39.6% vs 48.5%). MCS was not impaired in either group. After 2 y, PCS, presenteeism, WPL and AI significantly improved in both groups; absenteeism only in axSpA. In multivariable analysis, axSpA (vs non-axSpA) was associated with 22% less WPL (incidence rate ratio [95% CI]: 0.78 [0.62; 0.98]) and 18% less AI (0.82 [0.69; 0.97]). CONCLUSION: HRQoL and work productivity are more impaired in non-axSpA (vs axSpA) at baseline and still after 2 y. Although most outcomes improve in both groups, axSpA is associated with larger improvements in work productivity and activity impairment.
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OBJECTIVES: To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis (r-axSpA). METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort, inclusion criteria r-axSpA and ≥1 radiographic spinal syndesmophyte, were studied. MRI of the full spinal was performed at baseline, 1 and 2 years. PE/FJ inflammatory lesions and FJA were assessed per vertebral unit (VU) level by three readers. With multilevel time-lagged autoregressive generalised estimated equations, the association between PE/FJ inflammation and the subsequent development of FJA was investigated, taking the reader and VU levels into account. RESULTS: Out of the 58 patients with at least 2 reader scores available, mean age 49 (SD 10) years, 84% men, 59% had baseline PE inflammation, 24% had FJ inflammation and 26% had FJA. PE inflammation was more prevalent in the lower thoracic spine and FJ inflammation in the upper thoracic spine. VU with PE or FJ inflammation showed subsequent new FJA in two and one VU levels, respectively. The probability of developing FJA doubled with prior FJ inflammation. In multilevel analysis, FJ inflammation was associated with subsequent FJA (OR=3.8, 95% CI: 1.5 to 9.8), while no association was found between PE inflammation and new FJA (OR=1.2 (0.6-2.4)). CONCLUSIONS: FJ inflammation is rare in severe r-axSpA, but when present, the likelihood of developing subsequent FJA is over three times higher compared with FJ without inflammation. This finding contributes to the understanding of the relationship between inflammation and ankylosis at the same anatomical location in patients with axSpA.
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Anquilose , Espondiloartrite Axial , Inflamação , Imageamento por Ressonância Magnética , Articulação Zigapofisária , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Anquilose/etiologia , Anquilose/diagnóstico por imagem , Adulto , Seguimentos , Espondiloartrite Axial/etiologia , Espondiloartrite Axial/diagnóstico , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/patologia , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/complicações , RadiografiaRESUMO
OBJECTIVE: The objective of this study was to evaluate the impact of protocol violations in the treat-to-target group in the Tight Control in Spondyloarthritis (TICOSPA) trial and to compare the proportion of patients optimally treated according to the Assessment of Spondyloarthritis International Society (ASAS)/EULAR 2016 recommendations for patients with axial spondyloarthritis (axSpA) between the treat-to-target versus usual care (UC) arms. METHODS: This study was a cluster-randomized, controlled 48-week trial including patients with axSpA who fulfilled the ASAS criteria, had an Axial Spondyloarthritis Disease Activity Score >2.1, and were biologic disease-modifying antirheumatic drug naive. Eighteen axSpA expert centers were randomly allocated to one treatment arm: (a) treat-to-target prespecified management strategy (four-week visits), and (b) UC treatment decisions at the rheumatologist's discretion (12-week visits). Protocol violations in the treat-to-target arm and the fulfillment of the 2016 ASAS/EULAR recommendations in both arms were evaluated at every visit. ASAS Health Index (ASAS-HI) and disease activity outcomes at 48 weeks were compared between treat-to-target violators versus nonviolators. Patients treated according to the ASAS/EULAR recommendations were compared between both arms. RESULTS: A total of 160 patients initiated the trial (80 patients with treat to target; 80 patients with UC). In the treat-to-target arm, 51.2% patients violated the protocol at least once (62.2% of violations resulting in maintenance/reduction of treatment against protocol). After 48 weeks, treat-to-target violators versus nonviolators showed similar ratios of ASAS-HI improvement. The proportion of patients managed according to the ASAS/EULAR recommendations after the first 12 weeks were 63.9% versus 61.8% for the treat-to-target and UC arms, respectively. CONCLUSION: Protocol violations in the treat-to-target arm in the TICOSPA trial were frequent, although they did not have an impact on the rate of the primary outcome. The groups with UC was optimally treated, partly explaining the nonachievement of the primary objective in the TICOSPA trial.
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PURPOSE OF REVIEW: This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). RECENT FINDINGS: A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. SUMMARY: Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.
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Anti-Inflamatórios não Esteroides , Antirreumáticos , Espondiloartrite Axial , Humanos , Antirreumáticos/uso terapêutico , Espondiloartrite Axial/tratamento farmacológico , Espondiloartrite Axial/diagnóstico , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Progressão da Doença , Anticorpos Monoclonais/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: Upadacitinib improved the signs and symptoms of non-radiographic axial spondyloarthritis (nr-axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT-AXIS 2 nr-axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr-axSpA in SELECT-AXIS 2. METHODS: Patients aged at least 18 years diagnosed with nr-axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52-week double-blind period. Efficacy was assessed using non-responder imputation incorporating multiple imputation (NRI-MI) and as-observed analyses for binary endpoints, and mixed-effects model repeated measures for continuous endpoints. RESULTS: Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI-MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI-MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. CONCLUSION: Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit-risk profile of upadacitinib treatment for nr-axSpA.
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BACKGROUND: Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. METHODS: In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. FINDINGS: Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). INTERPRETATION: Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. FUNDING: Research Council of Norway and South-Eastern Norway Regional Health Authority.
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Antirreumáticos , Artrite Reumatoide , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Redução da Medicação , Noruega/epidemiologia , Indução de Remissão , Resultado do Tratamento , Adolescente , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). METHODS: Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. RESULTS: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. CONCLUSION: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.
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Adalimumab , Anticorpos Monoclonais Humanizados , Antirreumáticos , Espondiloartrite Axial , Medicamentos Biossimilares , Progressão da Doença , Radiografia , Humanos , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Pessoa de Meia-Idade , Medicamentos Biossimilares/uso terapêutico , Espondiloartrite Axial/tratamento farmacológico , Espondiloartrite Axial/diagnóstico por imagem , Resultado do Tratamento , Coluna Vertebral/diagnóstico por imagem , Método Duplo-CegoRESUMO
OBJECTIVE: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. METHODS: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. RESULTS: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [ß(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later. CONCLUSION: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points ⢠Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. ⢠Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. ⢠Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. ⢠Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit.
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Antirreumáticos , Artrite Reumatoide , Progressão da Doença , Radiografia , Indução de Remissão , Índice de Gravidade de Doença , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antirreumáticos/uso terapêutico , Idoso , Ultrassonografia , Resultado do Tratamento , AdultoRESUMO
OBJECTIVES: To compare the long-term outcomes of three phenotypes of axial SpA (axSpA). METHODS: Patients with a clinical diagnosis of axSpA from the DESIR cohort were grouped into three phenotypes at baseline: 'Pure axSpA' ('Axial'), 'axSpA with peripheral signs' ('IBP+Peripheral') and 'axSpA at risk' ('At risk') by latent class analysis. Clinical and imaging data were collected up to 5 years. Clinical outcomes, measured in each visit, included disability (BASFI) and quality of life (QoL; SF36). Imaging outcomes included inflammatory and structural lesions on MRI and radiographs of spine and SIJ. The association between phenotype membership at baseline and each outcome was tested in multivariable GEE models. RESULTS: In total, 576 patients with axSpA were included. 'At risk' patients had worse disability and QoL than 'Axial' patients over time. For instance, 'At risk' patients had on average 0.4 more points in BASFI over time than 'Axial' patients [ß (95 % CI): 0.4 (0.2; 0.7)]. This difference was mostly noted in female patients who were HLA-B27 positive. In addition, the difference between the 'At risk' and 'Axial' phenotypes was higher in patients receiving bDMARDs than in those not (ß=0.6 vs 0.5), since BASFI improved more in 'Axial' (∆BASFI: -1.3) than in 'At risk' (∆BASFI: -0.9) treated patients. There were no differences in disability and QoL between 'Axial' and 'IBP+Peripheral' patients. Imaging outcomes were worse in the 'Axial' phenotype than in the others over time. CONCLUSION: Patients with 'axSpA at risk' show worse self-reported outcomes over time and are less likely to benefit from anti-inflammatory treatment than those with a classical axSpA phenotype.
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Espondiloartrite Axial , Imageamento por Ressonância Magnética , Fenótipo , Qualidade de Vida , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Espondiloartrite Axial/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Estudos de Coortes , Radiografia , Índice de Gravidade de Doença , Articulação Sacroilíaca/diagnóstico por imagemRESUMO
OBJECTIVE: To assess which definition of remission best predicts good radiographic outcome (GRO) and good functional outcome (GFO) in rheumatoid arthritis, focusing the updated American College of Rheumatology/European Alliance of Associations for Rheumatology criteria. MATERIAL AND METHODS: Meta-analyses of individual patient data (IPD) from randomised controlled trials (RCTs). Six definitions of remission were considered: (1) Boolean with Patient Global Assessment (PGA)≤1 (Boolean); (2) Simplified Disease Activity Index (SDAI)≤3.3; (3) Clinical Disease Activity Index (CDAI)≤2.8; (4) Boolean with PGA≤2 (Updated-Boolean); (5) Boolean with Physician Global Assessment (PhGA≤1) replacing PGA (Boolean-PhGA) and (6) Boolean excluding PGA (3VBoolean). GRO was defined as a worsening ≤0.5 units in radiographic score and GFO as a no worsening in Health Assessment Questionnaire (HAQ), that is, ∆HAQ-DI≤0.0 units. Relationships between each remission definition at 6 and/or 12 months and GRO and GFO during the second year were analysed. Pooled probabilities for each outcome for each definition and their predictive accuracy were estimated. RESULTS: IPD from eight RCTs (n=4423) were analysed. Boolean, SDAI, CDAI, Updated-Boolean, Boolean-PhGA and 3VBoolean were achieved by 24%, 27%, 28%, 32%, 33% and 43% of all patients, respectively. GRO among patients achieving remission ranged from 82.4% (3VBoolean) to 83.9% (SDAI). 3VBoolean showed the highest predictive accuracy for GRO: 51.1% versus 38.8% (Boolean) and 44.1% (Updated-Boolean). The relative risk of GFO ranged from 1.16 (Boolean) to 1.05 (3VBoolean). However, the proportion of GFO correctly predicted was highest for the 3VBoolean (50.3%) and lowest for the Boolean (43.8%). CONCLUSION: 3VBoolean definition provided the most accurate prediction of GRO and GFO, avoiding the risk of overtreatment in a substantial proportion of patients without increment in radiographic damage progression, supporting the proposal that 3VBoolean remission is preferable to guide immunosuppressive treatment. The patient's perspective, which must remain central, is best served by an additional patient-oriented target: a dual-target approach.
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Artrite Reumatoide , Terapia de Imunossupressão , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/uso terapêuticoRESUMO
OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.
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Antirreumáticos , Artrite Psoriásica , Artrite Psoriásica/tratamento farmacológico , Humanos , Antirreumáticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Metotrexato/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
OBJECTIVES: To obtain an overview of recent evidence on efficacy and safety of pharmacological treatments in psoriatic arthritis (PsA). METHODS: This systematic literature research (SLR) investigated the efficacy and safety of conventional synthetic (cs), biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in patients with PsA. A systematic database search using Medline, EMBASE, Cochrane CENTRAL was conducted to identify relevant articles published since the previous update in 2019 until 28 December 2022. Efficacy was assessed in trials while for safety observational data were also considered. Adverse events of special interest were infections (including herpes zoster, influenza and tuberculosis), malignancies, major adverse cardiovascular events, venous thromboembolisms, liver disease, laboratory changes and psychiatric adverse events. No meta-analyses were performed. RESULTS: For efficacy, of 3946 articles screened, 38 articles (30 trials) were analysed. The compounds investigated included csDMARDs (leflunomide, methotrexate), bDMARDs inhibiting IL17 (bimekizumab, brodalumab, ixekizumab, izokibep, secukinumab,), IL-23 (guselkumab, risankizumab, tildrakizumab), IL-12/23 (ustekinumab) as well as TNF (adalimumab, certolizumab-pegol, etanercept, infliximab, golimumab) and Janus Kinase inhibitors (JAKi) (brepocitinib, deucravacitinib, tofacitinib, upadacitinib). The compounds investigated were efficacious in improving signs and symptoms of PsA, improving physical functioning and quality of life. For safety, 2055 abstracts were screened, and 24 articles analysed: 15 observational studies and 9 long-term follow-ups of trials, assessing glucocorticoids, TNFi, IL-17i, JAKi, IL-12/23i and PDE4i (apremilast). Safety indicators were generally coherent with the previous SLR in 2019. CONCLUSION: The results of this SLR informed the task force responsible for the 2023 update of the European Alliance of Associations for Rheumatology recommendations for pharmacological management of PsA.
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Antirreumáticos , Artrite Psoriásica , Artrite Psoriásica/tratamento farmacológico , Humanos , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Guias de Prática Clínica como Assunto , Produtos Biológicos/uso terapêuticoRESUMO
OBJECTIVE: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies. METHODS: Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses. RESULTS: Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs. CONCLUSION: The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.
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OBJECTIVE: (1) To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort. METHODS: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers' assessments. RESULTS: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients (P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively. CONCLUSION: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738, NCT01648907].
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Espondiloartrite Axial , Etanercepte , Imageamento por Ressonância Magnética , Radiografia , Articulação Sacroilíaca , Humanos , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Masculino , Espondiloartrite Axial/diagnóstico por imagem , Espondiloartrite Axial/tratamento farmacológico , Etanercepte/uso terapêutico , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Índice de Gravidade de Doença , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The Berlin algorithm was developed to help diagnosing axial spondyloarthritis (axSpA), but new studies suggest some features typical of SpA are less specific than previously assumed. Furthermore, evidence is lacking for other SpA subtypes (e.g. peripheral SpA). We aimed to review the evidence on the performance of SpA features for diagnosing each SpA subtype. METHODS: Systematic literature review of studies reporting the diagnostic performance of ≥ 1 SpA feature in patients with suspected SpA. The external reference was the rheumatologist's diagnosis of SpA. Meta-analysis was performed, separately for each SpA subtype, to estimate pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios. Meta-regression assessed the effect of covariates (e.g. feature's prevalence) on each feature's performance. RESULTS: Of 13 844 articles screened, 46 were included. Sacroiliitis on magnetic resonance imaging, damage on pelvic radiographs and elevated C-reactive protein (CRP) had the best balance between LR+ and LR- (LR + 3.9-17.0, LR- 0.5-0.7) for diagnosing axSpA. HLA-B27 had an LR+ lower than anticipated (LR + =3.1). Inflammatory back pain (IBP) had low LR + (LR+â¼1), but substantially decreased the likelihood of axSpA when absent (LR-=0.3). Conversely, peripheral features and extra-musculoskeletal manifestations showed high LR + (LR+ 1.6-5.0), but were as common in axSpA as no-axSpA (LR-â¼1). The specificity of most features was reduced in settings when these were highly prevalent. Limited data precluded a detailed analysis on diagnosing other SpA subtypes. CONCLUSION: Imaging features and CRP have good diagnostic value for axSpA. However, the specificity of other features, especially HLA-B27 and IBP, is lower than previously known.
RESUMO
OBJECTIVES: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. METHODS: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). MAIN OUTCOME: axSpA diagnosis with LoC≥7 (d-axSpA) at 2y. RESULTS: In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. CONCLUSION: A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients.
Assuntos
Espondiloartrite Axial , Sacroileíte , Espondilartrite , Espondilite Anquilosante , Humanos , Masculino , Reumatologistas , Sacroileíte/diagnóstico por imagem , Antígeno HLA-B27 , Espondilartrite/diagnóstico , Espondilartrite/diagnóstico por imagem , Dor nas Costas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Espondilite Anquilosante/diagnósticoRESUMO
OBJECTIVES: To determine if there were differences in the Assessment of SpondyloArthritis international Society Health Index (ASAS HI) scores between patients classified as radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA), and to identify factors associated with higher ASAS HI scores in both disease phenotypes. METHODS: This study was an ancillary analysis of the ASAS HI international validation project performed in 23 countries. Patients were included if they were ≥18 years of age and diagnosed with axSpA. Univariable and multivariable analysis were performed to determine if ASAS HI scores differed between the axSpA phenotypes, and to identify other variables associated with ASAS HI scores. We also tested for potential interactions between the axSpA phenotype and significant variables identified through the multivariable regression. RESULTS: A total of 976 patients were included, with 703 having r-axSpA and 273 nr-axSpA. Patients with r-axSpA reported higher (worse) ASAS HI scores compared with those with nr-axSpA (6.8 (4.4) vs 6.0 (4.0), p=0.02), but the axSpA phenotype was not associated with ASAS HI scores in the multivariable regression (ß: -0.19, 95% CI: -0.56 to 0.19). Female gender, having worse physical function (Bath Ankylosing Spondylitis Functional Index), disease activity (Ankylosing Spondylitis Disease Activity Score) and anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) were associated with higher ASAS HI scores. No interactions were found to be significant. CONCLUSION: Overall health and functioning are similarly affected in patients with r-axSpA and nr-axSpA. Female patients, having worse physical function, disease activity, anxiety and depressive symptoms were independently associated with higher ASAS HI scores.
Assuntos
Espondiloartrite Axial não Radiográfica , Espondilartrite , Espondilite Anquilosante , Humanos , Feminino , Espondilite Anquilosante/diagnóstico , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Ansiedade , FenótipoRESUMO
BACKGROUND: The Computed Tomography Syndesmophyte Score (CTSS) was developed as a reliable and sensitive tool to assess syndesmophytes in low-dose CT images of the entire spine in patients with axial spondyloarthritis (axSpA). The original paper provided sparce examples of the CTSS grades. OBJECTIVES: Provide an atlas tailored to assist readers in understanding and employing the CTSS method. METHODS: In this paper, illustrations of the different grades and views of the CTSS are presented. CTSS is used to measure bone formation in the spine of patients with axial spondyloarthritis (axSpA), in the form of syndesmophytes. In both the sagittal and coronal planes, syndesmophytes can be graded from 0 to 3 over 23 vertebral units starting at C2 and ending at S1. The CTSS ranges from 0 (absence of axSpA-related syndesmophytes) to 552 (total ankylosis of the spine). RESULTS: The current atlas contains low-dose CT images of the spine without lesions (for reference) and all grades of syndesmophytes in different planes used in the CTSS. Examples are arranged per spinal segment (cervical, thoracic and lumbar). CONCLUSIONS: These images can be used to assist any reader in the assessment of syndesmophytes on (low-dose) CT in patients with axSpA.
Assuntos
Espondiloartrite Axial , Humanos , Coluna Vertebral , Osteogênese , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. METHODS: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. RESULTS: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%). CONCLUSIONS: At Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ. TRIAL REGISTRATION NUMBER: NCT03928704; NCT03928743.