ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

BACKGROUND A link between primary pulmonary hypertension (PPH) and autoimmune disorders has been postulated. To investigate this relation, we performed immunofluorescent antinuclear antibody tests (ANA) and serological human leukocyte antigen (HLA)-A, B, C, DR, and DQ typing on two groups of Caucasian children with unexplained pulmonary hypertension (PHT) and their parents. METHODS AND RESULTS Group 1 consisted of 17 children with PPH including two patients with familial PPH and three patients with trivial congenital pulmonary to systemic communications. Group 2 consisted of 13 children with advanced PHT and anatomically large congenital pulmonary to systemic communications (PHT + shunt). Both groups had comparably severe pulmonary vascular disease documented by cardiac catheterization. The following statistically significant data (p less than 0.05) were obtained when the study groups were compared with those published for normal controls. Although positive ANAs and varying titers of autoantibodies were found in both groups of children and mothers (not fathers), +ANAs were only significant for the maternal groups. The PPH (group 1) children had increased frequencies of HLA-DR3, DRw52, and DQw2 and decreased DR5, whereas the group 2 (PHT + shunt) children (also their parents) had no statistically significant alterations in any of the DR or DQ alleles. The PPH mothers had decreased DQw3, an allele in linkage disequilibrium with DR5. CONCLUSIONS These immunogenetic data suggest that childhood PPH appears to be associated with the major histocompatibility complex alleles HLA-DR3, DRw52, and DQw2. This newly found correlation of juvenile PPH with these alleles adds this disease to the DR3+ group of autoimmune diseases. Further studies are needed to determine whether there is also an immunological or autoimmune component in some children with PHT + shunt lesions because this group lacked an HLA association.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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.

A 65-year-old female diabetic patient with wet gangrene on left great toe developed skin eruptions and blebs over her limbs and lower abdomen after receiving three doses of tablet linezolid + cefuroxime (600mg+500 mg). The skin eruptions and blebs completely resolved fourteen days after discontinuation of tablet Linezolid + Cefuroxime. Based on her presentation (Skin eruptions and blebs), we consider that the condition was a result of linezolid+ cefuroxime administration. While the pathophysiology of these cutaneous reactions is not completely understood, clinicians should be vigilant to allow early detection of these problems. The causality of this adverse reaction was determined by using Naranjo's criteria and World Health Organization Probability scale and was found to be possible and the severity of this reaction was determined by using the Modified Hartwig and Siegel scale and was found to be moderate (Level 3b) reaction. Although, Linezolid is known to cause dermatological reactions like rashes but the reports of leucocytoclastic vasculitis are rare. Thus, our case report of linezolid + cefuroxime induced leucocytoclastic vasculitis add newer information. Physician should be vigilant for the potential of drug to cause some rare side-effect like leucocytoclastic vasculitis on similar age groups, so that a safer alternative treatment can be started.