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.

Considering a Biologic: What's a Clinician to Do? Screening and Laboratory Monitoring for Biologic Therapies in the Treatment of Psoriasis.

Biologic therapies have revolutionized the treatment of psoriasis; however, these immunomodulatory therapies may increase the risk of reactivation of latent and chronic infections. Tumor necrosis factor alpha (TNF-α) inhibitors, in particular, have been associated with the increased risk of reactivation of tuberculosis (TB) in patients with latent TB, as well as hepatitis B virus (HBV), in patients with chronic HBV infections. Currently, baseline TB tests are the only screening tests supported with strong evidence. High-grade evidence for HBV screening tests is lacking; however, these tests are sometimes performed in clinical practice. We describe current recommendations for screening tests prior to the initiation of biologic therapy.

Malnutrition and Associated Disorders in Tuberculosis and Its Therapy.

Tuberculosis (TB) has become the most important infectious disease to see resurgence worldwide. In 2014, there were 9.6 million documented cases worldwide with a mortality of almost 1.5 million (Global Tuberculosis Report 2014). One of the Millennium Development Goals set by the United Nations was the reversal of the TB epidemic, which has been achieved worldwide with an 18% lower incidence of TB globally compared to the incidence in the year 2000. Though efficient intervention has brought down the relative incidence and mortality of TB globally, the fact remains that one third of the world population has latent TB infection, and 10% of people with latent TB infection develop active TB at some point in their life (The Facts about Tuberculosis 1995). Risk factors that prompt the reactivation of latent TB into active TB are a compromised immune system, HIV, malnutrition, and use of tobacco. In developing and underdeveloped economies, malnutrition and undernutrition play a major role in subverting the immune system and reactivating the latent TB infection. Undernutrition is one of the major factors in India and Southeast Asia leading to an increase in TB infections. Once tuberculosis sets in, it leads to an increase in metabolism and a decrease in appetite that compounds the already present malnutrition. Drawing on previous studies, we have aimed at understanding the relationship between malnutrition and TB infection and making minimal recommendations for corrective action.

Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice.

Since the introduction of biologics for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and psoriasis (Pso) an increased risk of tuberculosis (TB) reactivation in patients with latent tuberculosis infection (LTBI) has been recorded for anti-TNF agents, while a low or absent risk is associated with the non-anti-TNF targeted biologics. To reduce this risk several recommendation sets have been published over time, but in most of them the host-related risk, and the predisposing role to TB reactivation exerted by corticosteroids and by the traditional disease-modifying anti-rheumatic drugs has not been adequately addressed. Moreover, the management of the underlying disease, and the timing of biologic restarting in patients with TB occurrence have been rarely indicated. A multidisciplinary expert panel, the Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy (SAFEBIO), was constituted, and through a review of the literature, an evidence-based guidance for LTBI detection, identification of the individualized level of risk of TB reactivation, and practical management of patients with TB occurrence was formulated. The literature review confirmed a higher TB risk associated with monoclonal anti-TNF agents, a low risk for soluble receptor etanercept, and a low or absent risk for non-anti-TNF targeted biologics. Considering the TB reactivation risk associated with host demographic and clinical features, and previous or current non-biologic therapies, a low, intermediate, or high TB reactivation risk in the single patient was identified, thus driving the safest biologic choice. Moreover, based on the underlying disease activity measurement and the different TB risk associated with non-biologic and biologic therapies, practical indications for the treatment of RA, PsA, AS, and Pso in patients with TB occurrence, as well as the safest timing of biologic restarting, were provided.

Latent tuberculosis infection in patients with chronic plaque psoriasis: evidence from the Italian Psocare Registry.

BACKGROUND: The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated. OBJECTIVES: To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment. METHODS: Data were obtained from the Psocare Registry on those patients (n = 4946) with age > 18 years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis. RESULTS: Latent tuberculosis infection was diagnosed in 8·3% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 4·3% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralen-ultraviolet A (P < 0·05). Independent factors associated with LTBI were male sex [odds ratio (OR) 1·30, 95% confidence interval (CI) 1·04-1·62; P = 0·02], age over 55 years (OR 2·93, 95% CI 2·18-3·93; P < 0·001) and being entered into a conventional treatment (OR 3·83, 95% CI 3·10-4·74; P < 0·001). Positive history of tuberculosis was seen in 1% of patients (n = 49). CONCLUSIONS: The nationwide prevalence of LTBI in Italian patients with psoriasis candidate to systemic treatment is high, and screening is recommended prior to biological treatment.

Outcome of latent tuberculosis infection in solid organ transplant recipients over a 10-year period.

BACKGROUND: Screening and therapy of latent tuberculosis infection (LTBI) is recommended in solid organ transplant (SOT). However, there are limited data on the tolerability of LTBI therapy pretransplant and posttransplant. We studied the tolerability of LTBI therapy and effectiveness of a centralized LTBI treatment program in a low-risk population. METHODS: Provincial TB and transplant databases were retrospectively reviewed for LTBI therapy referrals in SOT candidates and recipients over a 10-year period. Using univariate logistic regression, we examined factors associated with failure to complete therapy and followed patients for active TB. RESULTS: From 2001 to 2010, 200/461 SOT candidates referred to the TB program (43.4%) were eligible for therapy for LTBI. Eleven patients refused therapy. The remaining patients (n=189) were initially prescribed isoniazid (73%), rifampin (12.7%), or another regimen (14.3%). Adequate LTBI therapy occurred in 122 (64.5%). Patients who were liver transplant candidates or recipients were less likely to complete therapy than nonliver transplant patients (OR, 0.20; P<0.001) as were patients treated in the posttransplant phase (OR, 0.47; P=0.034). Liver enzyme elevation led to discontinuation of therapy more often in liver transplant candidates and recipients (OR, 10.48; P<0.001) and posttransplant treatment (OR, 3.50; P=0.019). In 599.4 patient-years of follow-up posttransplant (mean, 4.9 year/patient), there were no cases of active TB. CONCLUSION: A centralized referral program for LTBI therapy in transplant candidates is effective to prevent TB reactivation posttransplant. A significant proportion of liver transplant candidates and recipients do not tolerate standard LTBI therapy. Alternative therapies for these patients should be evaluated.

Comprehensive tuberculosis screening program in patients with inflammatory arthritides treated with golimumab, a human anti-tumor necrosis factor antibody, in Phase III clinical trials.

OBJECTIVE: Reactivation of Mycobacterium tuberculosis infection is a major complication in patients treated with anti-tumor necrosis factor (anti-TNF) agents. We report on the 5 cases of active tuberculosis (TB) that developed in the Golimumab Phase III Program (3 with rheumatoid arthritis, 1 with psoriatic arthritis, and 1 with ankylosing spondylitis) through 1 year among 2,210 patients receiving golimumab. METHODS: Data from global studies were used for an in-depth evaluation of the 5 cases of TB through week 52. Integrated safety data were evaluated for potential hepatotoxicity in patients treated with anti-TB therapy. RESULTS: No active TB developed among 317 patients receiving golimumab and treated for latent TB with isoniazid. Active TB occurred in 5 patients not treated with isoniazid by week 52 (in 2 patients by week 24); all of the patients had negative TB screening tests (per the local guidelines) and resided in countries with high background rates of TB. No deaths were due to TB. Across all of the groups (placebo and golimumab), alanine aminotransferase and aspartate aminotransferase elevations occurred in greater proportions of patients treated for latent TB infection versus not treated; elevations were largely mild (<3 times the upper limit of normal). CONCLUSION: Comprehensive TB screening kept the number of active TB cases relatively low despite conducting the studies in TB-endemic regions. Treatment for latent TB infection appeared effective, since no patients treated for latent TB had TB reactivation. Concurrent treatment with golimumab and anti-TB medication was generally well tolerated. Clinicians should remain vigilant for development of active TB after initiation of TNF inhibitors, since prompt diagnosis and treatment can improve outcomes.

Screening of tuberculosis before biologics.

Using anti-TNF has significantly improved the management of chronic inflammatory rheumatism. However, there is clear evidence that this treatment increases the risk of reactivating tuberculosis. The intradermal tuberculin skin test (ITT) and interferon-γ-release assays (IGRAs) are currently used to detect latent tuberculosis infection. The results of ITT are difficult to analyze in patients vaccinated with Bacille Calmette-Guérin (BCG) and because of variation in test administration and reading. Numerous authors have compared the sensitivity and specificity of IGRA and ITT, including in two recent meta-analyses and one literature review. These authors, however, compared different populations with different ITT positive thresholds (5, 10, and 15mm). We performed a meta-analysis of studies in which the threshold was 15mm, the recommended level in France. The sensitivity of QuantiFERON, T-spot, and ITT was 79% (IC 76%-83%), 84% (IC 75%-95%), and 69% (IC 65%-73%), respectively. In France, it is recommended to detect latent tuberculosis infection on the basis of history taking, physical examination, 5-unit ITT, and lung X-ray. This screening leads to treating 20%-30% of patients, with considerable adverse-effects. Because of the sensitivity and specificity of IGRAs, it is no longer justified to systematically perform TST for detection of tuberculosis before initiating anti-TNF treatment.