Safety and Efficacy of Golimumab in Indian Patients with Active Spondyloarthritis of Ankylosing Spondylitis or Psoriatic Arthritis: A Multicenter, Noncomparative, Open-Label, Real-World Study.

BACKGROUND: The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitor therapy for most common rheumatological diseases, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in controlled clinical trials is well-studied. This study evaluated subcutaneous (SC) golimumab in Indian patients with active spondyloarthritis (SpA) of AS or PsA in a real-world setting. MATERIALS AND METHODS: This phase 4, multicenter, prospective, non-comparative, interventional, 24-week study was performed in patients (age ≥18 years) with active SpA of AS or PsA (NCT03733925). Golimumab 50 mg was given subcutaneously to the patients every 4 weeks. Safety was assessed. The proportion of patients with AS and PsA achieving ≥20% improvement in the Assessment of SpA International Society 20 (ASAS20) criteria and American College of Rheumatology 20 (ACR20) responses, respectively, at weeks 14 and 24 were efficacy endpoints. RESULTS: Of the 100 patients enrolled (men: 78 [78.0%]; mean age: 36.7 [12.02] years), 94 (94.0%) patients completed the study. Treatment-emergent adverse events with golimumab were observed in 29/100 (29.0%) patients, and nasopharyngitis and upper respiratory tract infection (5.0% each) were the most common (≥5%). Deaths were not reported. At week 14, 74.5% (95% confidence interval [CI]: 59.7; 86.1%) of patients with AS and 84.6% (95% CI: 69.5; 94.1%) of patients with PsA achieved ASAS20 and ACR20 responses, which were sustained at week 24 (ASAS20: 66.0% [95% CI: 50.7, 79.1%]; ACR20: 93.2% [95% CI: 81.3, 98.6%]), respectively. CONCLUSION: Golimumab (50 mg) administered subcutaneously was safe and effective in Indian patients with active SpA of AS or PsA during the 24-week study period with no new safety signals.

Common mental disorders in South Asian patients with systemic sclerosis: a CIS-R-based cross-sectional study.

There are not many studies looking at psychological impact of physical morbidities amongst patients with systemic sclerosis. Our aim was to describe the prevalence of common mental disorders (CMD) in systemic sclerosis patients, as against the population prevalence of CMDs. We also wanted to assess the utility of revised clinical interview schedule (CIS-R), a standardised interview technique for screening CMDs in systemic sclerosis (SSc). We prospectively recruited 93 consecutive patients fulfilling the 2013 ACR/EULAR criteria for systemic sclerosis from our single tertiary care centre. They were interviewed using CIS-R interviewing technique. These patients were assessed for the presence of psychiatric symptoms and presence of common mental disorders. Various associations of documented mental health issues and ICD-10-based psychiatric diagnosis were also analysed. A total of 29 (31%) out of 93 individuals with systemic sclerosis had a common mental disorder as per the earlier defined CIS-R cut off score of 12 and above. Fatigue (50.5%) and sleep issues (43%) were the commonest symptoms. Thirty-four patients (33.6%) fulfilled a total of 39 ICD-10 psychiatric diagnoses. Total CIS-R score is significantly associated with duration of Scleroderma in univariate analysis (p = 0.019), but there was no significant association on a multivariate analysis. Depression [18.3% as against 5% in Asian Indian general population], followed by obsessive compulsive disorder (OCD) [15.1% as against 0.7% in general population in India] were the top two ICD-10 psychiatric diagnosis in SSc. The occurrence of both depression and OCD, therefore, are far in excess compared to community prevalence. Additionally, modified CIS-R cut off of 10 instead of 12 can also improve the sensitivity (94%) of this screening interviewing tool for an ICD-10 psychiatric diagnosis. Depression is 3.4 times and OCD is 20 times commoner in our cohort of SSc than general population in India. A modified CIS-R cut-off score of 10 may further help in early recognition of these mental disorders in SSc and their referral to a psychiatrist.

Comparison of safety, efficacy and cost between oral pulse cyclophosphamide versus intravenous cyclophosphamide pulse therapy in severe systemic lupus erythematosus.

OBJECTIVES: The aim of this study is to compare efficacy, toxicity and cost between oral and intravenous cyclophosphamide (CYC) pulse therapy in inducing remission (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] <3) in severe SLE. METHODS: We retrospectively checked the hospital records of patients between the years 2000 and 2018, who had been administered oral cyclophosphamide pulse and intravenous (IV) cyclophosphamide pulse. SLEDAI at baseline and after 6 months of therapy were noted. The statistical analysis was done using Mann-Whitney U test. The cost was also calculated. RESULTS: We included 45 patients in this study, 21 in the oral pulse group and 24 in the IV group. The median age of patients in the oral and IV groups were 29 (interquartile range [IQR] 22-37) and 26 (IQR 19.25-0.75) years respectively. Median SLEDAI at baseline was comparable between the 2 groups (oral 18.0 [IQR 15.0-26.0]; IV 14.5 [IQR 11.0-20.0] P = .151). At the end of 6 months of treatment, it was 0.0 (IQR 0.0-4.0) in the oral group, as against 2.0 (IQR 0.0-5.5) in IV group (P = .676). There was no major adverse event in either group. Oral cyclophosphamide pulse therapy was more economical as compared to IV cyclophosphamide [630 Indian National rupees( INR)/ 8.85 US dollars(USD) in the IV arm and 50 INR/0.7 USD in the oral arm] (P < .001). CONCLUSION: This study concludes that oral cyclophosphamide pulse therapy is an economical option and there was no difference in efficacy and safety between oral cyclophosphamide pulse therapy and IV pulse cyclophosphamide therapy.

Saliva microbiome in primary Sjögren's syndrome reveals distinct set of disease-associated microbes.

OBJECTIVE: This study systematically aims to evaluate the salivary microbiome in patients with primary Sjögren's syndrome (pSS) using 16S rRNA sequencing approach. METHODS: DNA isolation and 16S rRNA sequencing was performed on saliva of 37 pSS and 35 control (CC) samples on HiSeq 2500 platform. 16S rRNA sequence analysis was performed independently using two popular computational pipelines, QIIME and less operational taxonomic units scripts (LoTuS). RESULTS: There were no significant changes in the alpha diversity between saliva of patients and controls. However, four genera including Bifidobacterium, Lactobacillus, Dialister and Leptotrichia were found to be differential between the two sets, and common between both QIIME and LoTuS analysis pipelines (Fold change of 2 and p < .05). Bifidobacterium, Dialister and Lactobacillus were found to be enriched, while Leptotrichia was significantly depleted in pSS compared to the controls. Exploration of microbial diversity measures (Chao1, observed species and Shannon index) revealed a significant increase in the diversity in patients with renal tubular acidosis. An opposite trend was noted, with depletion of diversity in patients with steroids. CONCLUSION: Our analysis suggests that while no significant changes in the diversity of the salivary microbiome could be observed in Sjögren's syndrome compared to the controls, a set of four genera were significantly and consistently differential in the saliva of patients with pSS. Additionally, a difference in alpha diversity in patients with renal tubular acidosis and those on steroids was observed.

Unique clinical and autoantibody profile of a large Asian Indian cohort of scleroderma-do South Asians have a more aggressive disease?

AIM AND METHODS: A single-centre retrospective study was conducted using electronic medical records (EMR) of inpatients and outpatients with the diagnosis of "scleroderma" or "systemic sclerosis" visiting our clinic over the preceding 5 years. RESULTS: A total of 327 patients' charts met our selection criteria; 301 were females. The median (IQR (inter quartile range)) age at onset of first non-Raynaud's symptom was 34.67 (27-43) years and median (IQR) disease duration prior to presentation to our department was 2.5 (1-5) years. Of these, 310 (94.8%) belonged to diffuse systemic sclerosis variety, 13 (4%) had limited systemic sclerosis, and 4 (1.2%) were of sine scleroderma type. A total of 289/302 (95.7%) patients were positive for ANA; of them, 245/327 (74.9%) were Scl-70 antibody-positive and 4% were CENP antibody-positive. Interstitial lung disease (ILD) was present in 288/327 (88.1%) patients. Among patients with available baseline forced vital capacity (FVC) data, 20% had a normal lung function and 28.4% had severe restriction. Pulmonary hypertension as assessed by echocardiography was present in 8.1% of patients. A significant association of Scl-70 antibody positivity with the presence of interstitial lung disease (ILD) (p = 0.000) and pulmonary hypertension (p = 0.035) was seen. On the other hand, presence of CENP antibody showed a protective trend against muscle weakness and/or muscle enzyme elevation (p = 0.052). Presence of arthritis was protective against development of digital ulceration (p = 0.021) and PAH (0.004). Patients younger than 40 years of age had significantly higher frequency of Scl-70 positivity (p = 0.038), whereas CENP antibody positivity was more likely in those aged > 40 years (p = 0.002). CONCLUSION: Younger age of onset and high prevalence of Scl-70 antibody are unique South Asian features common with large Indian, Thai, and Chinese series. High prevalence of ILD is a feature common to Indian and Chinese series. Strong correlation of Scl-70 antibody with younger age and pulmonary hypertension were unique features of our cohort. KEY POINTS: • Asian Indian scleroderma patients are younger by 2 decades compared to Caucasian series. • Higher prevalence of Scl-70 antibody, its association with young age, interstitial lung disease and pulmonary hypertension are features of our cohort. • High prevalence of interstitial lung disease (88.1%) was noted ; among those with baseline spirometry data (141/327), two thirds(66%) had moderate to severe restriction. • Younger age at onset, higher prevalence of Scl-70 antibody are features common to other Indian, Thai and Chinese series.