Will Apriso (mesalamine) lower fecal calprotectin levels in a patient with ulcerative colitis or do these levels fluctuate regardless of treatment?

Will Apriso Lower Fecal Calprotectin in Ulcerative Colitis?

Yes, Apriso (mesalamine) will lower fecal calprotectin in ulcerative colitis when there is active inflammation, but it is only FDA-approved for maintenance therapy at 1.5 g/day, which may be insufficient for treating active disease with elevated calprotectin. 1, 2

Understanding Apriso's Role and Limitations

Apriso is specifically approved only for maintenance of remission, not for induction therapy. 1, 2 This is a critical distinction because:

• The maximum approved dose of Apriso is 1.5 g/day 2
• This dose falls well below the standard induction dose of 2.4-3 g/day recommended for active disease 1
• Low-dose mesalamine (<2 g/day) is significantly less effective than standard doses (≥2 g/day) for both induction and maintenance 1, 2

Evidence That Mesalamine Lowers Fecal Calprotectin

When adequate doses of mesalamine are used, fecal calprotectin does decrease significantly with treatment response:

• In one RCT of 52 patients with quiescent UC but elevated fecal calprotectin (>50 mg/g), escalating mesalamine by 2.4 g/day resulted in normalization of fecal calprotectin in 27% versus only 4% who continued stable dosing 1
• A prospective study of 95 patients with mild-to-moderate UC treated with 4.8 g/day mesalamine showed mean fecal calprotectin decreased from 437 to 195 over 12 weeks (P < 0.001) 3
• In patients with active rectal inflammation treated with mesalamine suppositories, median fecal calprotectin significantly decreased in those achieving clinical and endoscopic remission (P < 0.0001) 4

Fecal Calprotectin Does Not Fluctuate Randomly

Fecal calprotectin reflects actual intestinal inflammation and does not fluctuate without reason:

• Patients with UC in symptomatic remission but elevated fecal calprotectin (usually >150 mg/g) are 4.4 times more likely to relapse compared to those with normal levels (95% CI, 3.48-5.47) 1
• In patients maintaining remission on mesalamine suppositories, fecal calprotectin remained at low levels and did not significantly change during 40-week follow-up 4
• In patients who relapsed, fecal calprotectin elevated 8 weeks before clinical relapse was diagnosed 4
• Elevated fecal calprotectin (≥55 μg/g) predicted relapse with 88% sensitivity and 80% specificity 4

Clinical Algorithm for Using Apriso

If the patient is in remission with normal fecal calprotectin:

• Apriso 1.5 g/day is appropriate for maintenance 1, 2
• Monitor fecal calprotectin every 6-12 months 1

If the patient has elevated fecal calprotectin (>50-150 mg/g) despite being asymptomatic:

• Apriso alone is insufficient 2
• Escalate to standard-dose mesalamine (2.4-4.8 g/day) using a different formulation like Delzicol, Asacol-HD, or Lialda 1, 2
• Consider adding rectal mesalamine (at least 1 g/day) for distal disease 1, 2

If the patient has active symptoms with elevated fecal calprotectin:

• Do not use Apriso for induction 1, 2
• Use high-dose mesalamine (4.8 g/day) which shows superior efficacy (RR 0.75 vs 0.84 for standard dose) 1, 2
• If no improvement after 10-14 days of rectal bleeding or 40 days without complete remission, add oral prednisone 40 mg/day or budesonide MMX 9 mg/day 2

Critical Pitfalls to Avoid

Underdosing with Apriso for active disease: The 1.5 g/day maximum dose is below the therapeutic threshold for treating inflammation 1, 2

Assuming calprotectin fluctuates randomly: Elevated levels indicate subclinical inflammation that predicts relapse and requires treatment escalation 1, 4

Delaying escalation: Persistent elevation of fecal calprotectin despite symptomatic remission warrants dose optimization, not watchful waiting 1