Frequency of Elevated Fecal Calprotectin Levels in Psoriatic Arthritis.

Frequency of Elevated Fecal Calprotectin Levels in Psoriatic Arthritis and Its Predictive Role for Inflammatory Bowel Disease Occurrence: a Prospective, Long-term, Controlled Study.

Background.Recent epidemiologic studies have shown an association between psoriasis, psoriatic arthritis (PsA) and inflammatory bowel diseases (IBD). Recently, measurement of fecal calprotectin (FC) demonstrated a good sensitivity and specificity for intestinal inflammation.

Primary objective of present study was to evaluate the presence of occult bowel inflammation in patients with PsA as expressed by elevated levels of FC. Secondary objectives were to investigate the correlation between the levels FC and clinical and laboratory features, and the outcome of CF-positive patients in terms of IBD development.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases; Psoriatic Arthritis
• Intervention / Treatment: Diagnostic test: Fecal calprotectin assay

Detailed Description

A number of studies evaluated the presence of occult intestinal inflammation by using FC assay in patients with axial SpA. In 2000, a study conducted in PsA patients without bowel symptoms showed at mucosa biopsies the presence of microscopic changes, increase in lamina propria cellularity, consisting of plasma cells and lymphocytes, and lymphoid aggregates.Present prospective case-control study was designed to investigate occult intestinal inflammation by using FC assay in consecutive patients with PsA at onset, and who had no abdominal symptoms. Five Italian Centers contributed to patients recruitment adopting the same inclusion and exclusion criteria over a 3 year period.

FC levels were measured at baseline with Bühlmann fCAL Turbo, Switzerland® kit. This automated method is a particle enhanced turbidimetric immunoassay employing polyclonal antibodies. The manufacturer cut-off for FC positivity was 50 μg/g, with a sensitivity of 100% and a specificity of 53.1%.

The number of patients developing IBD was evaluated at the end of follow-up. Clinical and laboratory data collection was centralized and two experts statisticians performed the data analysis.

Statistical analysis. All demographic, clinical, and laboratory data were collected and descriptive statistics, presented as mean value and standard deviation, were calculated using Microsoft ® Office Excel for Windows and ©2019 Minitabs, LLC for Windows. Chi-square test was used for categorical variables. FC test sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. Bayes's theorem was used to calculate the 95% confidence interval (95%CI). Correlations were calculated using Spearman's correlation (rs). P values ≤ 0.05 were accepted as statistically significant.

The median follow-up was 30 months.

• Study Type: Observational
• Enrollment (Actual): 259

Contacts and Locations

Study Locations

• Italy
  • Tuscany
    • Prato, Tuscany, Italy, 59100
      • Fabrizio Cantini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Both cases and controls were abdominal symptom-free.

Description

Inclusion Criteria:

• age >18 years
• absence of any abdominal symptoms or diarrhoea
• non-steroidal anti-inflammatory drug (NSAIDs) interruption 10 days before enrollment
• Corticosteroids (CS) at stable low dose (prednisone 10 mg/day or equivalent) during the preceding 2 weeks were permitted in both groups.

Exclusion Criteria:

• age < 18 years
• previous diagnosis of CD or UC or current diagnosis of infectious colitis
• previous therapy with traditional DMARDs or any biologic therapies
• CS at high doses.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case patients; All consecutive, new patients older than 18 years with PsA (CASPAR criteria) at onset observed over 3-year period, who had any abdominal symptoms.	Diagnostic test: Fecal calprotectin assay; FC levels were measured at baseline with Bühlmann fCAL Turbo, Switzerland® kit.
Controls; All consecutive new patients meeting the ACR/EULAR 2010 classification criteria for rheumatoid arthritis (RA) at onset.	Diagnostic test: Fecal calprotectin assay; FC levels were measured at baseline with Bühlmann fCAL Turbo, Switzerland® kit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of elevated FC levels in cases and controls	Comparison of FC levels between cases and controls	3 YEARS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations of FC levels with laboratory data	Spearman's correlation (rs)	3 YEARS
The percentage of patients developing IBD over the follow up	The occurrence of IBD over the follow up	3 YEARS

Collaborators and Investigators

• Sponsor: Hospital of Prato
• Collaborators: Giulia Franchi,Department of Rheumatology, Hospital of Prato; Maurizio Benucci,S.Giovanni di Dio Hospital; Raffaele Scarpa, Rheumatology Unit, University of Naples Federico II, Naples; Francesco Caso, Rheumatology Unit, University of Naples Federico II, Naples; Rosario Foti,Rheumatology Unit, A.O.U. Policlinico Vittorio Emanuele, Catania; Antonio Carletto,Rheumatology Unit, AOUI, Verona.; Elisa Visalli,Rheumatology Unit, A.O.U. Policlinico Vittorio Emanuele, Catania; Laura Niccoli,Department of Rheumatology, Hospital of Prato

Publications and helpful links

General Publications

• Fu Y, Lee CH, Chi CC. Association of Psoriasis With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. JAMA Dermatol. 2018 Dec 1;154(12):1417-1423. doi: 10.1001/jamadermatol.2018.3631.
• Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015 Jan;67(1):128-39. doi: 10.1002/art.38892.
• Klingberg E, Strid H, Stahl A, Deminger A, Carlsten H, Ohman L, Forsblad-d'Elia H. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther. 2017 Feb 2;19(1):21. doi: 10.1186/s13075-017-1223-2.
• Adarsh MB, Dogra S, Vaiphei K, Vaishnavi C, Sinha SK, Sharma A. Evaluation of subclinical gut inflammation using faecal calprotectin levels and colonic mucosal biopsy in patients with psoriasis and psoriatic arthritis. Br J Dermatol. 2019 Aug;181(2):401-402. doi: 10.1111/bjd.17745. Epub 2019 May 6. No abstract available.
• Scarpa R, Manguso F, D'Arienzo A, D'Armiento FP, Astarita C, Mazzacca G, Ayala F. Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel symptoms. J Rheumatol. 2000 May;27(5):1241-6.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2016
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): December 11, 2019
• Last Update Submitted That Met QC Criteria: December 9, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Gastroenteritis; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Inflammatory Bowel Diseases; Arthritis, Psoriatic; Intestinal Diseases
• Other Study ID Numbers: HPrato-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No