Is premature treatment escalation harmful?

Is Premature Treatment Escalation Harmful?

Premature treatment escalation without proper assessment can lead to unnecessary interventions, increased costs, and potential harms, but the greater risk in most clinical contexts is delayed escalation in truly deteriorating patients.

Context-Dependent Risk-Benefit Analysis

The harm of premature escalation depends critically on the clinical context:

In Inflammatory Bowel Disease and Rheumatologic Conditions

Early escalation to advanced therapies is generally beneficial and not considered "premature" when disease activity is documented. 1

• In moderate-to-severe ulcerative colitis, guidelines suggest early use of advanced therapies rather than gradual step-up after failure of 5-aminosalicylates 1
• Treatment escalation should occur within 3 months if symptomatic response is inadequate, with assessment for biochemical remission at 3-6 months and endoscopic improvement at 6-12 months 1
• In pediatric Crohn's disease, the CALM trial demonstrated that tight control with treatment escalation based on symptoms AND biomarkers achieved significantly higher mucosal healing rates (46%) compared to symptom-driven decisions alone (30%) 1
• For axial spondyloarthritis, patients with active disease despite NSAIDs should move to biologic DMARDs without unnecessary delay 1

In Acute Hospital Deterioration

The evidence strongly suggests that delayed escalation is far more harmful than premature escalation. 2, 3, 4

• In a study of 144 unexpected deaths, cardiac arrests, and unintended ICU admissions, the escalation protocol was adhered to in only 8% of cases, with monitoring frequency violations in 81% 4
• Treatment Escalation Plans (TEPs) are associated with significant reductions in ICU admissions, non-beneficial interventions, harms, and complaints 2
• When TEPs were present, only 10% of patients had treatment escalated at the time of deterioration calls, compared to 20% without TEPs, and information was deemed sufficient in 77% versus 54% 3

Specific Harms of Premature Escalation

In Inflammatory Conditions

Empiric dose escalation without therapeutic drug monitoring can result in:

• Futile therapy with additional costs and delayed switch to more effective alternatives 1
• In patients with immune-mediated pharmacokinetic failure (established antibodies), additional drug exposure may cause immediate and delayed hypersensitivity reactions 1
• Potential misclassification due to suboptimally defined thresholds for drug concentration and antibodies 1

In Acute Care Settings

Inappropriate escalation can cause:

• Unnecessary, potentially painful treatments in patients where resuscitation would be futile 1
• Overtreatment of patients who are not actively bleeding or deteriorating 1
• Increased patient anxiety and family distress 1

The Greater Risk: Delayed Escalation

The preponderance of evidence indicates that under-escalation is the more common and harmful problem:

• Violations of escalation protocols were common prior to serious adverse events, with doctors not notified in 42% of cases and senior doctors/MET not notified appropriately in 52% 4
• Time constraints, understaffing, nurse confidence in managing deterioration independently, and fear of reprimands were identified as barriers to appropriate escalation 4
• In polyarticular juvenile idiopathic arthritis, prolonged periods of active disease increase risk of joint damage and impair quality of life, making early achievement of inactive disease critical 1

Algorithmic Approach to Appropriate Escalation

For Inflammatory Conditions:

1. Document objective disease activity using validated measures (JADAS-27 for JIA, Mayo score for UC, ASDAS for axSpA) 1
2. Assess at 3-month intervals for treatment response 1
3. Escalate if:
   • Clinical symptoms persist with objective inflammation (elevated biomarkers, endoscopic activity) 1
   • Poor prognostic features present (extensive disease, high inflammatory burden) 1
   • Therapeutic drug monitoring shows low trough levels without antibodies 1
4. Consider reactive TDM over empiric escalation when secondary loss of response occurs with anti-TNF therapy 1

For Acute Hospital Deterioration:

1. Implement Treatment Escalation Plans at admission for all patients, particularly those at risk 2, 3
2. Escalate promptly when:
   • Early warning scores trigger protocol thresholds 4
   • Active bleeding or hemodynamic instability present 1
   • Vital signs show deterioration trends 1, 4
3. Do NOT delay escalation due to:
   • Uncertainty about patient wishes (TEP should clarify this prospectively) 2
   • Fear of reprimands from senior staff 4
   • Overconfidence in managing deterioration at current care level 4

Common Pitfalls to Avoid

• Confusing "premature" with "appropriate early" escalation - in inflammatory diseases, early aggressive treatment to achieve remission prevents long-term complications 1
• Relying solely on clinical symptoms without objective measures of inflammation or deterioration 1
• Delaying escalation due to cost concerns when disease activity is documented - this leads to worse long-term outcomes and higher ultimate costs 1
• Failing to establish clear escalation criteria prospectively through TEPs or treatment protocols 2, 3
• Allowing non-clinical factors (staffing, fear of criticism, time constraints) to delay appropriate escalation 4