J Rheum Dis.  2021 Oct;28(4):202-215. 10.4078/jrd.2021.28.4.202.

Safety of Tacrolimus in Autoimmune Disease: Results From Post-marketing Surveillance in South Korea

• Yoo WH
• Lee SI
• Kim TH
• Sung JJ
• Kim SM
• Hua F
• Sumarsono B
• Park SH

• KMID: 2520433
• DOI: http://doi.org/10.4078/jrd.2021.28.4.202

Abstract

Objective
Tacrolimus, a macrolide immunosuppressant, is approved in Korea for the treatment of rheumatoid arthritis (RA), lupus nephritis (LN) and myasthenia gravis (MG). We report three prospective post-marketing surveillance studies of tacrolimus conducted in South Korea in these indications.
Methods
Studies were conducted according to South Korean Ministry of Food and Drug Safety requirements. Patients were followed up for the duration of the study (up to 4 years) or until treatment discontinuation. Occurrence and likely relationship with tacrolimus of adverse events (AEs), adverse drug reactions (ADRs; defined as AEs where causal relationship to tacrolimus could not be excluded) and serious AEs were recorded. Association of AEs with demographic and medical factors was evaluated by multivariable analysis.
Results
The studies included 740 (RA), 307 (LN) and 104 (MG) patients. The incidence of AEs was 12.7% in RA (64.2% of AEs potentially related to tacrolimus), 20.9% (37.8% potentially related) in LN and 29.8% (56.8% potentially related) in MG. The incidence of ADRs was 8.4%, 9.8% and 20.2%, respectively. Serious AEs were reported in 0.7%, 7.2% and 8.7%, respectively. The most common AEs were abdominal pain (RA), pharyngitis (LN) and diarrhea (MG). Unexpected AEs occurred in 3.5% of patients with RA, 2.9% in LN and 8.7% in MG; no pattern of unexpected AEs was apparent. Multivariable analysis demonstrated that patients with comorbidity had higher probability of experiencing an AE in RA and MG studies.
Conclusion
The incidence of AEs and the safety profile of tacrolimus in each indication was consistent with previous reports.

Keyword

Autoimmune disease; Post-marketing product surveillance; Safety; Tacrolimus

Figure

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  Figure 1 Odds ratios and 95% CIs for the probability of experiencing an adverse event in the multivariable analysis according to the medical characteristics of the patient (RA study). 1. Presence versus absence of complication or comorbidity; 2. Moderate or severe RA versus mild RA; 3. Presence versus absence of any antirheumatic or biologic drug withdrawn before tacrolimus administration; 4. Duration of illness: period shown versus <12 months. CI: confidence interval, RA: rheumatoid arthritis, RA: rheumatoid arthritis.

• 

  Figure 2 Odds ratios and 95% CIs for the probability of experiencing an adverse event in the multivariable analysis according to the medical characteristics of the patient (LN study). 1. Presence of previous illness versus unknown; 2. Absence of previous illness versus uncertain; 3. Presence versus absence of renal impairment; 4. Mild LN versus severe LN; 5. Moderate LN versus severe LN.

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  Figure 3 Odds ratios and 95% CIs for the probability of experiencing an adverse event in the multivariable analysis according to the medical characteristics of the patient (MG study). 1. Continuous variable; 2. Male versus female; 3. Stated Class versus Class 1; 4. Presence versus absence of previous illness; 5. Presence versus absence of current illness. CI: confidence interval, MG: myasthenia gravis, MGFA: Myasthenia Gravis Foundation of America.

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