Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics

Physician Burnout and Patient Satisfaction with Consultation in Primary Health Care Settings: Evidence of Relationships from a one-with-many Design

Physician burnout, as a prolonged response to chronic emotional and interpersonal stressors on the job, has been associated with suboptimal patient care and deterioration in the patient-provider relationship. Although prior studies have identified a range of factors associated with decreased patient satisfaction, most have been conducted in tertiary care settings, while staff burnout has been examined at the hospital unit-level. To examine the impact of physician burnout on patient satisfaction from consultation in the primary care setting, a cross-sectional survey was conducted in Western Greece. Using a one-with-many design, 30 physicians and 300 of their patients, randomly selected, responded to the survey. Results showed that patient satisfaction correlated significantly with physician emotional exhaustion (r = -.636, p<.01) and physician depersonalization (r = -.541, p<.01). Mixed-effects multi-level models indicated that 34.4% of total variation in patients' satisfaction occurred at the physician level, after adjustment for patients' characteristics. Moreover, physician emotional exhaustion and depersonalisation remained significant factors associated with patient satisfaction with consultation, after controlling for patient and physician characteristics. Patients of physicians with high-exhaustion and high depersonalisation had significantly lower satisfaction scores, compared with patients of physicians with low-exhaustion and low depersonalisation, respectively. Future studies need to explore the mechanisms by which physician burnout affects patient satisfaction