Intest Res.  2024 Jul;22(3):319-335. 10.5217/ir.2023.00071.

Association between oral corticosteroid starting dose and the incidence of pneumonia in Japanese patients with ulcerative colitis: a nation-wide claims database study

• Matsuoka K
• Inoue T
• Tsuchiya H
• Nagano K
• Iwahori T

• KMID: 2558192
• DOI: http://doi.org/10.5217/ir.2023.00071

Abstract

Background/Aims
A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by Japanese treatment guidelines (initial OCS prednisolone equivalent dose, 30–40 mg). This may relate to physician’s concern about infection, especially pneumonia including Pneumocystis jirovecii pneumonia (PJP), from high OCS doses. We assessed whether pneumonia incidence is increased with guideline-recommended OCS initial doses.
Methods
This retrospective cohort study used the Japan Medical Data Center claims database (2012–2021). The whole cohort consisted of all UC patients who started OCS during the study period meeting the inclusion and exclusion criteria. The matched cohort was created by propensity score matching; the lower (initial OCS dose < 30 mg), guideline-recommended (30–40 mg), and higher groups ( > 40 mg) in a 2:2:1 ratio. Pneumonia incidence in the primary analysis was evaluated in the matched cohort. A Poisson regression model determined pneumonia-related risk factors in the whole cohort.
Results
After screening, 3,349 patients comprised the whole cohort; 1,775 patients comprised the matched cohort (lower dose, n = 710; guideline-recommended dose, n = 710; higher dose, n = 355). The incidence of any pneumonia was low; no differences were observed in incidence rates across these dose subgroups. In total, 3 PJP cases were found in the whole cohort, but not detected in the matched cohort. Several risk factors for any pneumonia were identified, including age, higher comorbidities index, treatment in large facility and hospitalization.
Conclusions
The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups.

Keyword

Corticosteroids; Ulcerative colitis; Pneumocystis jirovecii pneumonia

Figure

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  Fig. 1. Study design. Index date: day of the first oral corticosteroids (OCS) prescription after the ulcerative colitis diagnosis during the selection period. Look-back period: a period of 6 months before the index date to examine the medical history and comorbidities and to assess the initial dose of OCS during the selection period. Follow-up period: a period after the index date to follow treatment status in ulcerative colitis and the occurrence of pneumonia.

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  Fig. 2. Flow diagram of study patient through the JMDC database. UC patients who did not experience pneumonia and antibiotic prescription within 6 months were extracted among individuals in the database. Overall, 3,349 patients were eligible for inclusion in this study. JMDC, Japan Medical Data Center; UC, ulcerative colitis; OCS, oral corticosteroid; 5-ASA, 5-aminosalicyclic acid; PSL, prednisolone; GL, guideline.

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  Fig. 3. Time series trends of oral corticosteroid (OCS) dose. Regardless of the initial dose, OCS were tapered and discontinued within 180 days in most patients. PSL, prednisolone.

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  Fig. 4. Incidence rate (IR; event/patient year) of any pneumonia and antibiotic prescription. Overall, the incidence of any pneumonia with antibiotic prescription was low and the incidence rates of any pneumonia were similar in all OCS treatment groups (in the lower dose, GL-recommended dose, and higher dose group, respectively). aAdjusted: using covariate factors of matching. OCS, oral corticosteroid; PSL, prednisolone; PY, patient year; IRR, incidence rate ratio; CI, confidence interval; GL, guideline.

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  Fig. 5. Time to pneumonia events in each oral corticosteroid (OCS) treatment group. The cumulative incidence of pneumonia was low in all OCS treatment groups within 6 months of OCS administration and did not differ across OCS treatment groups, however, the incidence of pneumonia tended to increase after 12 months of continuous OCS administration.

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  Fig. 6. Forest plot of crude and adjusted IRRs according to risk factors. Risk factors associated with any pneumonia were advanced age (≥65 years), higher CCI score, in large facilities with bed numbers >300 or 500, prophylactic TMP-SMX treatment, and being hospitalization at an index date. OCS, oral corticosteroid; PSL, prednisolone; BMI, body mass index; CCI, Charlson Comorbidity Index; 5-ASA, 5-aminosalicylic acid; 5-AZA, 5-azathioprine; 6-MP, 6-mercaptopurine; JAK, Janus kinase inhibitor; IRR, incidence rate ratio; CI, confidence interval.

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