Impact of biological therapy in reducing the risk of arthritis development in inflammatory bowel diseases.

OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.

Multidisciplinary Team Led by Joint Surgeons to Rapidly Identify Spondyloarthritis.

Context: Spondyloarthritis (SpA) is a group of chronic, inflammatory, rheumatic diseases of which axial SpA and peripheral SpA are the two main types. Patients that predominantly have manifestations of axSpA may have additional peripheral-arthritis symptoms, and vice versa. For these hard-to-diagnose SpA patients, symptoms can be nonspecific and difficult to identify, making it easy to miss a diagnosis or misdiagnosis patients, resulting in disability. Objective: The study intended to evaluate the value of a multidisciplinary team (MDT) led by the joint surgeons to rapidly identify spondyloarthritis (SpA). Design: The research team designed a controlled study that analyzed the clinical data of patients with spondyloarthritis. Setting: The study was conducted in the Department of Joint Surgery at Shandong Second Provincial General Hospital in Jinan, China. Participants: Participants were 113 SpA patients at the hospital between January 2019 and January 2020. Intervention: he research team divided participants into an intervention group, the MDT group that used that model to diagnose 83 participants and the control group with 30 participants, for whom diagnoses occurred using the conventional diagnostic model. Outcome Measures: The research team collected data on participants' number of visits and number of departments visited as well as determined the amount of time that elapsed before a diagnosis occurred. The team also measured C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI) at baseline and after 3 months and 6 months treatment. Results: In the MDT group, diagnoses included: (1) axial SpA (axSpA)-73 participants, and (2) peripheral SpA-10 participants, including three with reactive arthritis, two with uveitis, and five with psoriatic arthritis. Eight participants in that group were HLA-B27 positive, and 14 had complications from a latent tuberculosis infection. In the control group, diagnoses included: (1) axSpA-25 participants; and (2) peripheral SpA-5 participants, including three with psoriatic arthritis and two with reactive arthritis. Six participants in that group were HLA-B27 positive and four had complications from a latent tuberculosis infection. The number of visits, number of departments visited, and time to diagnosis in the MDT group were significantly lower than those in the control group (P < .001). After three and six months of treatment, the MDT group's CRP, ESR, BASDAI, and BASFI were significantly lower than those at baseline (P < .001). Conclusions: The MDT model of spondyloarthritis led by joint surgeons was accurate and efficient, allowing the medical personnel to quickly identify and intervene in SpA and provide effective treatment for patients. It's a diagnosis and treatment model worthy of promotion.

Tapering biologics in axial spondyloarthritis: A systematic literature review.

INTRODUCTION: The emergence of biologics has improved the management of patients with rheumatic disease, mainly with spondyloarthritis (SpA). Sustained remission has become a reachable goal thanks to the treat to target strategy. Contrary to rheumatoid arthritis, data on biologic optimization among SpA patients in remission is scarce and still a subject of debate. The main objective of this systematic review was to provide the most up-to-date published literature regarding biologic tapering in axial spondyloarthritis. METHODS: This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until December 20th 2021, and tackling tapering strategies of the biologics in patients with axial SpA were included RESULTS: Fourteen studies met the inclusion criteria. They were published between 2008 and 2020. The most studied molecules were Etanercept (ETN) (n = 13), Infliximab (IFX) (n = 6), Adalimumab (ADA) (n = 5), certolizumab pegol (CZP) (n = 2), Golimumab (n = 1) and ETN biosimilar. There are no studies published regarding anti-IL 17 tapering strategy. Patient-tailored dose reduction of anti TNF-α agents was successful in preserving stable low disease activity in most of the studies with remission rates ranging between 20.2 % and 93.7 %. Complete treatment discontinuation is associated with a high risk of flares. CONCLUSION: To conclude, published data indicate that a progressive tapering strategy for anti TNF-α therapy is successful among axial SpA in sustained remission. However, further studies with more homogenized tapering strategies are needed in order to ascertain the specific implication of each subset for a better holistic approach.

Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial.

OBJECTIVES: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. RESULTS: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. CONCLUSION: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib. TRIAL REGISTRATION NUMBER: NCT04169373.

Dual Blockade of TNF and IL-17A Inhibits Inflammation and Structural Damage in a Rat Model of Spondyloarthritis.

The tumor necrosis factor (TNF) and IL-23/IL-17 axes are the main therapeutic targets in spondyloarthritis. Despite the clinical efficacy of blocking either pathway, monotherapy does not induce remission in all patients and its effect on new bone formation remains unclear. We aimed to study the effect of TNF and IL-17A dual inhibition on clinical disease and structural damage using the HLA-B27/human ß2-microglobulin transgenic rat model of SpA. Immunized rats were randomized according to arthritis severity, 1 week after arthritis incidence reached 50%, to be treated twice weekly for a period of 5 weeks with either a dual blockade therapy of an anti-TNF antibody and an anti-IL-17A antibody, a single therapy of either antibody, or PBS as vehicle control. Treatment-blinded observers assessed inflammation and structural damage clinically, histologically and by micro-CT imaging. Both single therapies as well as TNF and IL-17A dual blockade therapy reduced clinical spondylitis and peripheral arthritis effectively and similarly. Clinical improvement was confirmed for all treatments by a reduction of histological inflammation and pannus formation (p < 0.05) at the caudal spine. All treatments showed an improvement of structural changes at the axial and peripheral joints on micro-CT imaging, with a significant decrease for roughness (p < 0.05), which reflects both erosion and new bone formation, at the level of the caudal spine. The effect of dual blockade therapy on new bone formation was more prominent at the axial than the peripheral level. Collectively, our study showed that dual blockade therapy significantly reduces inflammation and structural changes, including new bone formation. However, we could not confirm a more pronounced effect of dual inhibition compared to single inhibition.

Treatment of back pain in active axial spondyloarthritis with serial locoregional water-filtered infrared A radiation: A randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease primarily affecting the axial skeleton. OBJECTIVE: To evaluate the short-term effects of locoregional water-filtered infrared A radiation (sl-wIRAR) in the treatment of lower back pain in patients with axSpA. METHODS: Patients with active axSpA with non-steroidal anti-inflammatory drug (NSAID) therapy undergoing a 7-day multimodal rheumatologic complex treatment in an in-patient setting were eligible. Patients were randomly assigned to the intervention group (IG) receiving sl-wIRAR treatment of the back (2 treatments/day for 30 min each for 6 days) or to the control group (CG) receiving no treatment. Primary outcome was a between-group difference in pain after sl-wIRAR therapy measured on a numeric rating scale (NRS) (0 = no pain, 10 = worst pain). Secondary outcomes included an assessment of i) the onset and development of analgesic effects and an evaluation of whether sl-wIRAR ii) improved axSpA-specific well-being and iii) influenced serum cytokine levels. RESULTS: Seventy-one patients were enrolled, completed the trial and were analyzed (IG: 36 patients, CG: 35 patients). In the IG, there was a statistically significant change (p< 0.0005) in pain level [NRS] (1.6 ± 1.9 [5; 2]) from baseline (4.1 ± 2.4 [0; 8]) to trial completion (2.6 ± 2.0 [0; 7]) and a significant difference to the CG (p= 0.006). In the IG there was a significant improvement in axSpA-specific well-being (BAS-G) (p= 0.006). A physiologically relevant change in serum cytokine levels could not be observed. CONCLUSION: sl-wIRAR treatment can be useful in the treatment of patients with active axSpA as it leads to a rapid reduction of pain.

Ultrasound Doppler enthesitis shows sensitivity to change after biological therapy in spondyloarthritis and psoriatic arthritis patients.

OBJECTIVE: To explore the sensitivity to change in power Doppler (PD) enthesitis in active spondyloarthritis (SpA) and psoriatic arthritis (PsA) patients. METHOD: This was a longitudinal study in patients with SpA and PsA with active disease [patients starting or switching to biological disease-modifying anti-rheumatic drugs (bDMARDs)]. The MAdrid Sonographic Enthesitis Index (MASEI) was performed at baseline and at 3 and 6 month visits. The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. Reliability analysis among three readers was performed with ultrasound (US)-recorded videos. RESULTS: US examinations of 25 patients were included; 16 (64%) had SpA and nine (36%) PsA. The median (interquartile range, IQR) age was 49 (41-61) years, and 13 patients (52%) were female. The median (IQR) 28-joint Disease Activity Score of 3.6 (2.3-4.2), Bath Ankylosing Spondylitis Disease Activity Index of 6.7 (6.1-7.4), and C-reactive protein value of 8.2 (1.6-20) reflected moderate to high disease activity at baseline. Both MASEI and OMERACT PD enthesitis improved significantly at 3 and 6 month follow-up (p < 0.05) and showed sensitivity to change (standard error of measurement = 0.47 and 0.61, respectively). Improvement in clinical activity outcomes was significantly associated with decreases in MASEI and OMERACT PD enthesitis counts (p < 0.05). The MASEI and OMERACT PD definitions had excellent reliability (kappa = 0.918 and 0.865, respectively). CONCLUSION: PD enthesitis significantly improved at 3 and 6 month follow-up in patients undergoing bDMARD therapy. Both MASEI and OMERACT PD US enthesitis reflect response to treatment.

Epigallocatechin gallate regulates inflammatory responses and new bone formation through Wnt/ß-Catenin/COX-2 pathway in spondyloarthritis.

OBJECTIVE: Spondyloarthritis (SpA) is mainly characterized by bone erosion, new bone formation, inflammation and potential disability. Epigallocatechin gallate (EGCG) has been proved to be closely related with the regulation of inflammation and bone metabolism. However, whether EGCG could improve SpA remains unclear. METHODS: SpA animal model was established using proteoglycan. Cell proliferation were measured by CCK-8 assay. The mRNA expression levels of genes were detected using qRT-PCR, protein levels were assessed via western blotting and immunohistochemistry. ELISA assay was performed to examined the inflammatory cytokine release. Lesions in spine cartilage tissues were observed using hematoxylin-eosin (HE) and Safranin O staining. Alkaline phosphatase (ALP) assay and Alizarin Red S staining was used to investigate osteoblast mineralization. RESULTS: We found that EGCG could inhibit inflammation and new bone formation in SpA mice. Besides, inflammatory factor expression and osteogenic differentiation in osteoblasts isolated from SpA mice were also decreased by EGCG. Further, EGCG treatment suppressed the activation of Wnt/ß-Catenin/COX-2 pathway and the activator of this pathway partially reversed the effects of EGCG on inflammation and osteoblast differentiation. CONCLUSIONS: EGCG repressed inflammatory responses and new bone formation, and further improved SpA through Wnt/ß-Catenin/COX-2 pathway. Our findings may provide a new thought for the prevention and treatment of SpA.

Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT core outcome set: a meta-research study of trials included in Cochrane reviews.

The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: "physical function," "pain," "spinal mobility," "spinal stiffness," and "patient's global assessment" (PGA). The core set for clinical record keeping further includes the domains "peripheral joints/entheses" and "acute phase reactants," and the core set for DC-ART further includes the domains "fatigue" and "spine radiographs/hip radiographs." The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials.Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and "missing data") should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.

Predictive clinical-genetic model of long-term non-response to tumor necrosis factor-alpha inhibitor therapy in spondyloarthritis.

AIM: Tumor necrosis factor inhibitors (TNFi) are effective in controlling disease activity in spondyloarthritis (SpA). However, in a proportion of patients these treatments are ineffective or lead to adverse events. Recently, alternative therapies, such as interleukin (IL)-17 or IL-23 inhibitors, have emerged in the treatment of these pathologies. This study aimed to determine clinical and genetic predictors of non-response to TNFi treatment in 118 spondyloarthritis patients diagnosed according to Assessment in SpondyloArthritis International Society (ASAS) criteria. METHOD: From the literature, 41 single nucleotide polymorphisms (SNPs) were selected that had previously been associated with TNFi treatment response in spondyloarthropathies, rheumatoid arthritis and psoriasis. A clinical non-response was defined as a decrease of <50% of initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in axial involvement, or a reduction of less than 1.2 of initial Disease Activity Score of 28 joints-C-reactive protein (DAS28-CRP) in patients with only peripheral involvement. Univariate and multivariate hazard ratios (HR) were determined using Cox proportional hazard models to analyze the potential prognostic factors affecting non-response to TNFi treatment. RESULTS: The clinical factors that significantly increased the non-response rate were: global visual analog scale (VAS), CRP, BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), and the number of TNFi used. Only rs11591741 SNP showed an association with non-response. In the multivariate analysis, females had a non-response rate 4.46 times higher than males; each one-point increase in the BASFI index increased the non-response rate by 75%, and being a genotype GG vs GC or CC carrier was associated with an almost 4 times greater non-response rate. CONCLUSION: We developed a clinical-genetic model to identify SpA patients with a long-term non-response to TNFi therapy.

Nutritional profile of patients with chronic inflammatory diseases in the age of biologicals.

Tumor necrosis factor alpha (TNFα) has an important role in the body composition of patients with rheumatoid arthritis (RA), Crohn's disease (CD), and spondyloarthritis (SpA). We aimed to assess the nutritional profile of patients with RA, CD, and SpA undergoing remission with multiple therapies comparing to controls and to analyze the effect of anti-TNFα medications in the nutritional parameters of these patients. One hundred thirty-one patients were included: 44 with RA, 43 with CD, and 44 with SpA. Patients receiving anti-TNFα were compared with those receiving non-biological treatment as well as to controls. Nutritional profile included body mass index (BMI), waist circumference (WC), mid-upper arm circumference, and triceps skinfold measurement. Overweight and obesity were highly prevalent on three assessed groups. In patients with RA, BMI was > 25 kg/m2 in 74.9% patients and 49.2% controls (p < 0.0005); in CD, in 55.7% patients and 41.2% controls (p < 0.0001); and in SpA, in 68.1% patients and 43.5% controls (p < 0.0001). Central obesity was higher in all three disease groups when compared to healthy controls. There was no significant difference on nutritional parameters in patients using or not using anti-TNFα medications, except in patients with SpA, in which biologic therapy was significantly associated with lower BMI and WC, when compared to other therapies. Overweight, obesity, and elevated WC were more prevalent in patients with RA, CD, and SpA undergoing remission when compared to controls despite of used therapy. The use of biologic drugs in patients with SpA was associated with a lower BMI and lower WC.

Sacroiliac Joint Ankylosis in Young Spondyloarthritis Patients Receiving Biologic Therapy: Observation of Serial Magnetic Resonance Imaging Scans.

OBJECTIVE: To assess the temporal relationship between initiating biologic therapy and magnetic resonance imaging (MRI) scores of inflammation and structural damage in young patients with spondyloarthritis. METHODS: A local adolescent/young adult patient rheumatology database was searched for patients ages 12-24 years who had evidence of sacroiliitis on MRI and a clinical diagnosis of enthesitis-related arthritis (ERA) with axial involvement or nonradiographic axial spondyloarthritis. Patients treated with tumor necrosis factor inhibitor (TNFi) therapy who had undergone a minimum of 1 MRI scan before and 2 MRI scans after starting TNFi therapy (over ≥2 years) were included. Images of the sacroiliac joints were scored for inflammation and structural abnormalities (including erosions, fat metaplasia, and fusion). The effects of TNFi therapy and of time since initiation of TNFi therapy on inflammation and structural abnormalities were assessed using a mixed-effects regression analysis. RESULTS: Twenty-nine patients (ages 12-23 years) with ERA or nonradiographic axial spondyloarthritis who underwent TNFi therapy were included. Inflammation scores were significantly lower in patients receiving TNFi treatment (P = 0.013), but there was no significant effect of time from TNFi initiation on inflammation (P = 0.125). Conversely, there was no significant effect of active TNFi treatment on fusion scores (P = 0.308), but fusion scores significantly increased with time from TNFi initiation (P < 0.001); a similar positive relationship between time since biologic start and fat metaplasia scores was observed. CONCLUSION: TNFi therapy failed to prevent the eventual development of joint ankylosis in this cohort of young patients with spondyloarthritis, despite a substantial reduction in inflammation with TNFi therapy.

Recomendaciones de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en espondiloartritis axial / Recommendations by the Spanish Society of Rheumatology on the Use of Biological Therapies in Axial Spondyloarthritis

Objetivo: La aparición de nueva información sobre las terapias biológicas en la espondiloartritis axial (EspAax) ha impulsado una nueva revisión de las recomendaciones de la Sociedad Española de Reumatología (SER) basadas en la mejor evidencia posible. Estas nuevas recomendaciones pueden servir de referencia para reumatólogos implicados en el tratamiento de estos pacientes. Métodos: Se creó un panel formado por nueve reumatólogos expertos en EspAax, previamente seleccionados por la SER mediante una convocatoria abierta. Las fases del trabajo fueron: identificación de las áreas clave para la actualización del consenso anterior, análisis y síntesis de la evidencia científica (sistema modificado de Oxford, CEBM, 2009) y formulación de recomendaciones a partir de esta evidencia y de técnicas de consenso. Resultados: Esta revisión de las recomendaciones comporta una actualización en la evaluación de actividad de la enfermedad y objetivos de tratamiento. Incorpora también los nuevos fármacos disponibles, así como sus nuevas indicaciones, y una revisión de los factores predictivos de respuesta terapéutica y progresión del daño radiográfico. Finalmente, estas recomendaciones abordan también las situaciones de fracaso a un primer anti-TNF, así como la posible optimización de la terapia biológica. El documento incluye una tabla de recomendaciones y un algoritmo de tratamiento. Conclusiones: Se presenta la actualización de las recomendaciones SER para el uso de terapias biológicas en pacientes con EspAax

Objective: Recent data published on biological therapy in axial spondyloarthritis (axSpA) since the last publication of the recommendations of the Spanish Society of Rheumatology (SER) has led to the generation of a review of these recommendations based on the best possible evidence. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with axSpA. Methods: Recommendations were drawn up following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Centre for Evidence Based Medicine at Oxford. The level of agreement was established through the Delphi technique. Results: In this review, we did an update of the evaluation of disease activity and treatment objectives. We included the new drugs with approved therapeutic indication for axSpA. We reviewed both the predictive factors of the therapeutic response and progression of radiographic damage. Finally, we drafted some recommendations for the treatment of patients refractory to anti-tumor necrosis factor, as well as for the possible optimization of biological therapy. The document also includes a table of recommendations and a treatment algorithm. Conclusions: We present an update of the SER recommendations for the use of biological therapy in patients with axSpA

Complementary medicine for axial spondyloarthritis: is there any scientific evidence?

PURPOSE OF REVIEW: Majority of patients with axial spondyloarthritis (axSpA) report use of complementary and alternative medicine (CAM) therapies before and even after the diagnosis, due to perceived efficacy and wide-spread belief that these modalities lack side effects. In this review, we describe the available scientific evidence for the CAM therapies in axSpA. RECENT FINDINGS: Clinical trials of the CAM therapies in axSpA are generally hampered by small sample size, short duration, difficulties in blinding, lack of control groups and strong placebo effect. Nonetheless, exercise programs like Pilates and mind-body techniques such as Tai Chi may have favorable effect on the disease activity and function. Although not yet confirmed, the modulation of the microbiome with the help of probiotics or fecal transplant has face validity given the evolving scientific rationale. Diet has only limited role in the management of axSpA. Deep tissue massage, omega-3 fatty acids and Stanger bath were found to be useful in small studies. CAM therapies are not always entirely well tolerated, particularly the manipulative techniques like chiropractic and Tui-na in patients with advanced disease and osteoporosis. There are no trials of yoga in axSpA despite the wider acceptance and use of yoga as an effective mind-body technique. SUMMARY: Larger and better quality clinical trials of CAM therapies are needed to confirm their efficacy and safety in the management of axSpA and to include them in the 'mainstream' medicine.

Recommendations by the Spanish Society of Rheumatology on the Use of Biological Therapies in Axial Spondyloarthritis. / Recomendaciones de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en espondiloartritis axial.

OBJECTIVE: Recent data published on biological therapy in axial spondyloarthritis (axSpA) since the last publication of the recommendations of the Spanish Society of Rheumatology (SER) has led to the generation of a review of these recommendations based on the best possible evidence. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with axSpA. METHODS: Recommendations were drawn up following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Centre for Evidence Based Medicine at Oxford. The level of agreement was established through the Delphi technique. RESULTS: In this review, we did an update of the evaluation of disease activity and treatment objectives. We included the new drugs with approved therapeutic indication for axSpA. We reviewed both the predictive factors of the therapeutic response and progression of radiographic damage. Finally, we drafted some recommendations for the treatment of patients refractory to anti-tumor necrosis factor, as well as for the possible optimization of biological therapy. The document also includes a table of recommendations and a treatment algorithm. CONCLUSIONS: We present an update of the SER recommendations for the use of biological therapy in patients with axSpA.

Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study.

AIM: To report adalimumab (Ada) efficacy on articular-gastrointestinal disease and health-related quality of life (HRQoL) in patients with enteropathic spondyloarthritis (ES). METHODS: A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes (PROs) of the HRQoL questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor (TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests: (1) Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) for articular activity; (2) Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and partial Mayo (pMayo) score for gastrointestinal symptoms and activity; and (3) Health Assessment Questionnaire (HAQ), Patient Global Assessment (PGA) and Short Form-36 health survey (SF-36) questionnaires for PROs of the HRQoL. RESULTS: Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQoL scores, showed a significant improvement having been achieved at the earliest (6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES. CONCLUSION: Ada treatment, upon multidisciplinary (gastro-rheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQoL in patients affected by ES.

The evidence for microbiome manipulation in inflammatory arthritis.

The human body consists of millions of commensal bacteria (the microbiome), with the intestinal tract being the most prevalent site of colonization. This colonization process begins at birth, and despite numerous factors such as ageing, diet and drug use affecting the microbiome make-up, by adulthood the composition of the gut bacteria is relatively consistent across local populations. The recent advent of new scientific techniques has enabled us to explore how the microbiome affects health and, in particular, has shed light on the involvement of the microbiome in the pathogenesis of inflammatory disease. In this review we highlight the current evidence for microbiome manipulation in inflammatory arthritis in animal and human models and discuss potential therapeutics targeting the microbiome as treatment for these diseases.

Influenza and pneumococcal vaccine coverage in 584 patients taking biological therapy for chronic inflammatory joint: A retrospective study.

OBJECTIVES: To evaluate influenza and pneumococcal vaccine coverage in patients taking biological therapy for chronic inflammatory joint disease and to identify factors associated with the decision to administer these two vaccines. METHODS: Retrospective cross-sectional questionnaire study of a cohort of 584 patients taking biological therapy for chronic inflammatory joint disease (rheumatoid arthritis or spondyloarthritis). We studied the influenza and pneumococcal vaccine coverage rates, information about these vaccines given to patients by the primary-care physician and rheumatologist, and reasons for not administering the vaccines. RESULTS: Overall vaccine coverage rates were 44% for influenza and 62% for pneumococcus. Factors associated with being vaccinated were patient age, previous influenza vaccination, and patient information. Concern about adverse effects and absence of patient information by the primary-care physician and rheumatologist were associated with very low coverage rates. CONCLUSION: This study showed insufficient vaccine coverage rates, particularly against influenza, in a population at high risk because of exposure to biological therapy. Patient information by healthcare professionals about influenza and pneumococcal vaccination has a major impact and should be renewed as often as possible.

[Polymyalgia rheumatica update, 2015]. / Polymyalgia rheumatica update, 2015.

Polymyalgia rheumatica is an inflammatory musculoskeletal disorder of people aged 50 years or over, characterised by pain, aching and morning stiffness in the shoulder girdle and often hip girdle and neck. Marked systemic inflammation and rapid response to corticosteroid therapy are characteristic features. Giant cell arteritis is a well-known association of polymyalgia rheumatica. Recent clinical evidence and scientific results in the field have provided new challenges for rheumatologists. Besides the aspecific - although characteristic - proximal syndrome, less well recognizable and more variable distal musculoskeletal manifestations were observed. Magnetic resonance and ultrasound studies showed mild, remitting and non-erosive synovitis, with dominating inflammation of the extraarticular synovial structures. As no pathognostic sign is known, the diagnosis of polymyalgia rheumatica is based on its differential diagnosis, differentiation from the polymyalgia mimics; particularly from elderly onset inflammatory arthritides, such as elderly onset rheumatoid arthritis and late onset seronegative spondylarthritis. In 2012 the international polymyalgia rheumatica work group under the guidance of the American College of Rheumatology and European League Against Rheumatism elaborated new classification criteria, the scoring algorythm of which is based on clinical symptoms, with ultrasonography increasing the specificity. Corticosteroids remain the cornerstone of the therapy of polymyalgia rheumatica. No effective steroid-sparing drug has been found to date. Corticosteroids are generally needed for 1-1.5 years, though some patients have a chronic-relapsing course and require corticosteroids for several years. Well known corticosteroid-related side effects (diabetes, hypertension, hyperlipidaemia and osteoporosis) cause significant morbidity and economic burden on the society. Novel therapeautic approaches are on trial. Early recognition of the disease, early start of corticosteroids and a well-defined course, prevention and management of side effects are everyday tasks for rheumatologists and family doctors. Knowledge of polymyalgia rheumatica is essential for all medical specialties.