Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

OBJECTIVE: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients. We wanted to see if there is a similar phenomenon for Mycophenolate in SSc. METHODS: Twenty SSc patients, who were on a stable dose of MMF (1.5-3 g) underwent a sequential cross over study with MMF alone in the first month, followed by co-treatment with Ranitidine and then Esomeprazole in the second and third month respectively. Estimation of 12-hour area under curve (AUC) of Mycophenolic Acid (MPA) levels and total GI score were calculated at the end of each month and compared between the treatment arms. [Trial registration: CTRI/2020/06/025,939] RESULTS: Co-administration of esomeprazole was associated with 32.7% (mean difference = 22.28 µg h ml-1) reduction in mean AUC MPA, whereas ranitidine caused a reduction of 21.97% (mean difference = 14.93 µg h ml-1) in MPA AUC when compared to MMF without anti-acid therapies. The addition of ranitidine or esomeprazole resulted in significant reduction in the total GI score. CONCLUSION: Co-administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with SSc. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents are co-prescribed with MMF.

Factors associated with high cardiovascular risk in psoriatic arthritis and non-psoriatic spondyloarthritis.

To identify the association between traditional cardiovascular risk factors, diseases related factors, body composition and adipokines with high cardiovascular risk (HCVR) in psoriatic arthritis and non-psoriatic spondyloarthritis. This was a cross-sectional study involving age and BMI matched adults with psoriatic arthritis (PsA) (n = 56) and non-psoriatic spondyloarthritis (nPsA-SpA) (n = 58). Body composition using whole-body dual energy X-ray absorptiometry, adipokines and disease characteristics along with cardiovascular risk scoring QRISK3 and carotid intimal medial thickness (CIMT) was collected. Individuals with a QRISK3 ≥ 10% or CIMT of ≥ 75 percentile of the general population were categorised as HCVR. Predictors of HCVR were determined by logistic regression. HCVR was detected in 39 (34.2%) of the patients. After adjusting for all the factors, sarcopenia (aOR-15.83; 95% CI 1.16-215.48; p = 0.038) and presence of any traditional CV comorbidity (aOR: 18.97; 95% CI 1.63-221.29; p = 0.019) were associated with HCVR. nPsA-SpA had a 97% lesser chance of having HCVR as compared to PsA. The ROC curve analysis for the multiple logistic regression model which estimated the AUC as 0.787 (95% CI 0.701-0.874) and a P value < 0.001. Adipokine levels correlated well with body composition, but not with HCVR. PsA has a higher CV risk and the mechanisms for the same are poorly understood. Sarcopenia is an important determinant of HCVR and may be due to ectopic adipose tissue deposition in skeletal muscles. Focused physical therapy to prevent sarcopenia, optimum treatment of traditional CV risk factors and adequate disease control may help in preventing atherosclerosis in SpA.

Antibody responses after documented COVID-19 disease in patients with autoimmune rheumatic disease.

Patients with autoimmune rheumatic diseases (AIRD) are suspected to have less robust immune responses during COVID-19 due to underlying immune dysfunction and the use of immune-suppressive drugs. Fifty consecutive patients with a diagnosis of AIRD on disease-modifying drugs were included at around 30 days after a confirmatory test for COVID-19. Fifty controls matched one to one for age, sex, and severity of COVID-19 were also included at around 30 days after testing positive for COVID-19. Antibody titers for anti-spike protein IgG and anti-nucleocapsid protein IgG were estimated. Cases (mean age 45.9 ± 13; 76% females) and controls (mean age 45.9 ± 13; 76% females) had similar proportion of comorbidities. Of the cases, 4 had moderate and 1 had severe COVID-19, while 3 and 1 of controls had moderate and severe COVID-19 respectively. Positivity of anti-N IgG was similar between patients (80%) and controls (90%) (p = 0.26). Similarly, anti-S IgG was positive in 82% of patients and 86% of controls (p = 0.79). Both the antibodies were negative in seven (14%) patients and five (10%) of controls (p = 0.76, Fischer exact test). Only anti-N IgG titers were lower in patients as compared to controls. In four patients with rheumatoid arthritis, two with spondyloarthritis and one with eosinophilic fasciitis both antibodies were not detectable. They did not differ from the rest of the cohort in clinical characteristics. The patients with AIRD had adequate protective antibody responses to COVID-19 at a median of 30 days post-infection. Thus, the presence of AIRD or the use of immunosuppressants does not seem to influence the development of humoral immune response against COVID-19. Key Points • Patients with autoimmune rheumatic diseases (AIRD) are suspected to have less robust immune responses. • In our cohort of 50 patients with AIRD with confirmed COVID-19, only seven did not have detectable protective antibodies at 30 days post infection. • Patients with AIRD on immunosuppressants have adequate protective antibodies post COVID-19 disease, at rates similar to that in health controls.

Lupus retinopathy: a marker of active systemic lupus erythematosus.

Retinopathy in the context of systemic lupus erythematosus (SLE) is associated with severe disease and poorer prognosis. We studied retinopathy in our cohort of Indian lupus patients. Four hundred and thirty-seven patients fulfilling the Systemic Lupus International Collaborating Clinics-American College of Rheumatology-2012 criteria, attending the department of Clinical Immunology were enrolled under this cross-sectional study. A comprehensive clinical (including ophthalmological) examination and immunological profile were performed. Retinopathy was defined if cotton-wool spots, haemorrhages, vasculitis, retinal detachment or optic disc changes as papilledema, optic atrophy were present. Disease activity was assessed using SLE disease activity index (SLEDAI). Mean age of participants was 28.06 ± 9.7 years (93.1% females); median disease duration 12 months (Interquartile range-IQR 6.36). Forty-five (10.3%) had SLE associated retinopathy. Autoimmune haemolytic anaemia [31.1 vs 14.5%, p value 0.004, odd's ratio-OR (95% confidence interval-CI) 2.65 (1.33-5.29)], serositis [33.3 vs 18.9%, p value 0.023, OR (CI) 2.14 (1.11-4.10)], lupus nephritis [62.2 vs 40.8%, p value 0.006, OR (CI) 2.38 (1.26-4.50)], seizures [28.9 vs 12.8%, p value 0.004, OR (CI) 2.77 (1.36-5.65)] and median SLEDAI score (24 vs 12, p < 0.01) were significantly higher in those with retinopathy. On adjusted binary logistic regression, autoimmune hemolytic anemia, lupus nephritis and presence of antibodies to Smith antigen were predictors for retinopathy. Retinopathy is common in SLE, a marker of active disease with frequent renal involvement and should be screened for in all patients with lupus.