Does Gastrointestinal Adverse Drug Reaction Influence Therapeutic Effect in the Treatment of Rheumatoid Arthritis?

Abstract

Dear Editor:

A number of disease-modifying antirheumatic drugs (DMARDs) in Western medicine (WM) are available for the treatment of rheumatoid arthritis (RA).¹ Traditional Chinese Medicine (TCM) had been widely used in China for the treatment of RA. Tripterygium wilfordii Hook. F. and Yishen Juanbi tablets have been found to be effective in the treatment of RA and are marketed with the approval of the China State Food and Drug Administration.^2,3

DMARDs have shown significant toxicities, which leads to a high discontinuation rate of treatment. The most common adverse drug reactions (ADRs) are gastrointestinal (GI)-related symptoms.⁴ In CM, all therapy must be based on its pattern, which is classified after analyzing the symptoms. The GI symptoms could be a signal for CM pattern change if they showed up during the therapeutic process. Thus, exploring the correlation between the GI ADRs and therapeutic efficacy (ACR 20)* in the treatment of RA by analyzing randomized controlled trial data is important.

Patients of either sex, aged from 18 to 70 years old, were eligible for this study if they met the American College of Rheumatology (ACR) criteria for RA for at least 1 year and were classified into functional Class I, II, or III based on their current physical functions.⁵ Written, informed consent was obtained from every study patient. Within 14 days before randomization, all patients had a comprehensive medical examination.

All patients in the WM group took the following drugs with the dosage and administration methods as indicated: Briefly, diclofenac extended action tablet, 75 mg once a day after meals, and was discontinued when the severe joint pain become controlled; methotrexate, once a week with a starting dosage at 5 mg with addition of 2.5 mg each week and maintain dosage about 5 mg a week; sulfasalazine, twice a day with the starting dosage at 0.25 g and additional 0.5 g/day, the maintain dosage ranging from 0.5 g to 1 g, four times a day.

All patients in the TCM group took both of the following two Chinese medicines: Glucosidorum Tripterygll Totorum tablets, 10 mg each time, three times a day; and Yishen Juanbi tablets, 8 g each time, three times a day after meals.⁶

Safety was assessed at baseline, and at every 2 or 4 weeks thereafter throughout the 24-week treatment. Safety analyses included all randomized patients who received at least one dose of study medication and who underwent at least one safety assessment after baseline. All data were analyzed on a Statistics Analysis System (SAS Institute, Shanghai) 9.1 (order no. 195557) statistical package. The proportion of participants with adverse effects was analyzed using the χ² analysis.

Of 397 cases that received 24-week treatment, 203 were in the TCM group and 194 were in the WM group. Baseline demographics, including rheumatoid factor (RF), rest pain, joint tenderness score, joint swelling score, morning joint stiffness, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulin A (IgA), IgG, IgM, hands-grasp force, walking time in 20 m, patient global assessment, and physician global assessment were similar between the two groups except for age and disease duration.

The common GI ADRs included nausea and vomiting, gastralgia, stomach upset, diarrhea, fecal occult blood, anorexia, and dental ulcer. There was no difference in GI ADRs between the CM and WM groups (Table 1).

Table 1.

Case Numbers with Gastrointestinal (GI) Adverse Drug Reactions (ADRs) ^a

ADR	CM group	WM group
Nausea and vomiting	7	8
Gastralgia	8	7
Stomach upset	6	11
Diarrhea	4	0
Fecal occult blood	1	0
Anorexia	1	4
Dental ulcer	1	0

In the Chinese medicine (CM) group, there were 14 cases that showed GI ADRs, and 20 in the Western medicine (WM) group. More than one ADRs happening to 1 patient were noted as one ADR case, and some cases suffered from more than two ADRs.

The correlation between efficacy and ADRs is shown in Table 2. The effective rate in patients with GI ADRs was significantly lower than those without GI ADRs in the WM group after 24 weeks of treatment (p < 0.05).

Table 2.

Correlation Between Gastrointestinal Adverse Drug Reactions and Efficacy

	CM				WM
	n	Effective	Ineffective	Amotic	n	Effective	Ineffective	Amotic
12 w	14	3	8	3	20	3	11	6
24 w	14	6	5	3	20	5	8**	7

Effective rate based on the American College of Rheumatology 20 (ACR20) Core Data Set at 24-week treatment was 53.20% and 69.59%, respectively, in Chinese medicine (CM) and in Western medicine (WM), p < 0.01 (data not shown).

p < 0.05 with χ² analysis.

In conclusion, GI ADRs were inversely correlated with ther-apeutic efficacy in patients with RA treated with biomedical combination therapy, and influence of GI ADRs on the efficacy of treatment of RA with CM therapy was not found.

Footnotes

Acknowledgments

This study was supported jointly by the National Eleventh Five Year Support Project of China (2006BAI04A10), National Science Foundation of China (No. 90709007 and 30825047), and E-institutes of Shanghai Municipal Education Commission (No. E03008).

Disclosure Statement

No potential conflict of interest relevant to this article was reported.

*

ACR 20, The American College of Rheumatology 20 (ACR20) Core Data Set. Improvement criteria for the ACR Core Data Set are based on improvement of at least 20% in both tender and swollen joint counts, and three of the five additional measures.

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