A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis.
Patients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD.



Fecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period.



Fecal calprotectin >50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by <200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin.



Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD.



ClinicalTrials.gov identifier: NCT00858819 . Registered 9 March 2009. Last updated 28 May 2015.
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, S-413 46, Gothenburg, Sweden. eva.klingberg@vgregion.se.
Eva
E
Klingberg
Department of Internal Medicine, Södra Älvsborgs Sjukhus, Borås, Sweden.|Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Hans
H
Strid
Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Arne
A
Ståhl
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, S-413 46, Gothenburg, Sweden.
Anna
A
Deminger
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, S-413 46, Gothenburg, Sweden.
Hans
H
Carlsten
Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.|Sweden School of Health and Education, University of Skövde, Skövde, Sweden.
Lena
L
Öhman
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, S-413 46, Gothenburg, Sweden.|Rheumatology Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Helena
H
Forsblad-d'Elia
D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D053704:Capsule Endoscopy; D003113:Colonoscopy; D005243:Feces / Q000737:chemistry*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D000069285:Infliximab / Q000627:therapeutic use; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000150:complications*; D011795:Surveys and Questionnaires
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab
Ankylosing spondylitis; Crohn’s disease; Fecal calprotectin; Inflammatory bowel disease; Intestinal inflammation; Spondylarthritis; Ulcerative colitis