Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a multisystem disease that affects the joints and various organs, resulting in compromised quality of life and increased mortality. A wide spectrum of treatment options is available for RA. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are the first-line of treatment for RA, whereas tumor necrosis factor α inhibitors are commonly used as a second-line biological disease-modifying antirheumatic drug following inadequate response to csDMARDs. However, remission remains difficult to achieve. No single agent is effective for all patients. It is important to consider patients' comorbidities, perspectives, and preferences when selecting treatment.Interleukin 6 (IL-6) plays a prominent role in the pathophysiology of RA and is an important therapeutic target for RA. Tocilizumab and sarilumab are approved IL-6 inhibitors, which have demonstrated good efficacy and tolerability as combination therapy or monotherapy in RA patients with inadequate response to csDMARDs or tumor necrosis factor α inhibitors. Apart from alleviating joint symptoms, inducing remission, and reducing structural damage, tocilizumab and sarilumab exhibit additional advantages in alleviating extra-articular symptoms, such as fatigue and morning stiffness, and have positive effect on anemia and glucose metabolism. Additionally, evidence showed that certain patient subgroups, such as those with comorbidities including anemia and diabetes mellitus, those with early RA, those with high baseline IL-6 levels, those at high risk of tuberculosis infection, or those intolerant to methotrexate monotherapy, may benefit from IL-6 inhibition. Given these advantages, tocilizumab and sarilumab can be considered earlier as a rational choice for treating RA in suitable patients. Future clinical investigations will help refine the use of these agents.

Myositis-specific autoantibodies and their clinical associations in idiopathic inflammatory myopathies.

BACKGROUND: Myositis-specific autoantibodies (MSAs) have been found to be present predominantly in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the prevalence of MSAs and their associated complications in a cohort of patients with IIMs. METHODS: This was a multicentered prospective study. Consecutive adult Chinese patients with IIMs in the regional hospitals in Hong Kong were followed up from July 2016 to January 2018. Clinical characteristics, treatment history, and disease complications were documented. A commercially available immunoblot assay was used to detect the MSAs. RESULTS: Out of the 201 patients studied, at least one MSA was found in 63.2% of patients. The most common among the identified MSAs were the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) and the anti-transcriptional intermediary factor 1-gamma antibody (anti-TIF1-γ Ab) (both 13.9%), followed by anti-Jo-1 antibody (12.4%). Anti-MDA5 was present exclusively in dermatomyositis (DM) and was strongly associated with digital ulcers, amyopathy, and rapidly progressive interstitial lung disease (RP-ILD). Anti-TIF1γ was strongly associated with refractory rash and malignancy. Independent risk factors of RP-ILD included anti-MDA5 (OR 14.5), clinically amyopathic DM (OR 13.9), and history of pulmonary tuberculosis (OR 12.2). Cox regression analysis showed that anti-TIF1γ (HR 3.55), DM (HR 3.82), and family history of cancer (HR 3.40) were independent predictors of malignancy. CONCLUSIONS: MSA testing enables dividing of patients with IIMs into phenotypically homogeneous subgroups and prediction of potentially life-threatening complications.

DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.

OBJECTIVE: To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. METHODS: A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. RESULTS: 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. CONCLUSION: Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology.

The expanding range of treatment options for rheumatoid arthritis (RA), from conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to biological DMARDs (bDMARDs), biosimilar bDMARDs, and targeted synthetic DMARDs, has improved patient outcomes but increased the complexity of treatment decisions. These updated consensus recommendations from the Hong Kong Society of Rheumatology provide guidance on the management of RA, with a focus on how to integrate newly available DMARDs into clinical practice. The recommendations were developed based on evidence from the literature along with local expert opinion. Early diagnosis of RA and prompt initiation of effective therapy remain crucial and we suggest a treat-to-target approach to guide optimal sequencing of DMARDs in RA patients to achieve tight disease control. Newly available DMARDs are incorporated in the treatment algorithm, resulting in a greater range of second-line treatment options. In the event of treatment failure or intolerance, switching to another DMARD with a similar or different mode of action may be considered. Given the variety of available treatments and the heterogeneity of patients with RA, treatment decisions should be tailored to the individual patient taking into consideration prognostic factors, medical comorbidities, drug safety, cost of treatment, and patient preference.

Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis.

To report our experience in using rituximab (RTX) for treating refractory rapidly progressive interstitial lung disease (RP-ILD) complicating anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive amyopathic dermatomyositis (ADM). Medical records of four ADM patients with refractory RP-ILD treated with RTX therapy were reviewed retrospectively. All four patients were tested positive for anti-MDA5 Ab and failed to respond to high-dose systemic steroid and other intensive immunosuppressive therapies. Respiratory symptoms, lung function tests, and high-resolution computed tomography (HRCT) of the chest were compared before and after the first course of RTX. After RTX treatment, all four patients had improvement in the respiratory symptoms in terms of New York Heart Association classification. Two patients successfully had their supplementary oxygen therapy weaned off. The lung function tests were significantly better in all patients. The HRCT showed improvement in three patients while the other one remained static. The recalcitrant vasculitic rashes associated with the anti-MDA5 Ab were also better in all patients. The average daily prednisolone dose dropped from 20 to 6.25 mg post-treatment. None of the patients died throughout the follow-up period which ranged from 6 months to 2 years. However, two patients developed chest infection and one wound infection within 6 months after the RTX infusion. Our results suggest that RTX may be a useful therapy for anti-MDA5 Ab-positive ADM associated with RP-ILD. However, infection is the major risk.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

OBJECTIVE: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness. RESULTS: The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV. CONCLUSION: With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].