Positive Effects of Uyakujunkisan Therapy (Kampo Medicine) for Postherpetic Neuralgia With Concomitant Pregabalin: Two Case Reports With a Literature Review.

Context • The hallmark of herpes zoster (HZ) is a painful, blistering rash, but neuropathic pain can persist beyond the clearing of the rash and is diagnosed as postherpetic neuralgia (PHN), a chronic pain syndrome. However, the pain in PHN is often refractory to treatment. Objective • The study investigated the ability of Uyakujunkisan (UJS), or Kampo medicine, a traditional herbal medicine, to treat PHN successfully. Design • The study was observational, with discussion of 2 cases. Setting • The study took place in the Department of Japanese Oriental Medicine at Gunma Central and General Hospital (Maebashi, Gunma, Japan). Participants • The participants in cases 1 and 2 were a 70-y-old male and a 70-y-old female, respectively. The woman in case 2 also had rheumatoid arthritis. Both had been treated for HZ with antiviral drugs but continued to experience pain and were diagnosed with PHN. Intervention • Both participants were treated with a decoction of UJS that was administered 3 ×/d before meals. Outcome Measures • The patients completed a visual analogue scale. Results • In case 1, the patient's pain had almost disappeared after 8 wk of treatment. In case 2, the patient's pain had disappeared by 4 mo after starting the UJS treatment. Conclusions • Treatment with UJS may be a useful option as a therapeutic strategy for refractory PHN, especially in older adults.

Recent clinical applications of Japanese oriental (Kampo) medicine for rheumatoid arthritis: search for Kampo responder.

Rheumatoid arthritis (RA) is a heterogeneous disease. In rheumatology, researchers have not identified useful clinical markers to predict the effects of biological agents or of nonbiological, antirheumatic drugs before administration. Since the advent of biological agents, therapeutic strategies for RA have focused on early detection and early intensive treatment. Although responders to Japanese Oriental (Kampo) medicine exist, physicians first have had to diagnose RA using the practices of conventional medicine. They could identify those patients who would benefit from administration of Kampo medicine only by administering the treatment. Only the presence of a positive response could confirm the benefits for a particular individual. In this article, the author discusses the clinical importance of Kampo medicine within the context of the present RA classification criteria and therapeutic treatment and discusses the use of the basal value of anti-CCP antibody (aCCP) titer as a prognostic factor for use of Kampo medicine for RA. The author then defines a methodology for determining who should receive the treatment.

Benzofuran derivatives inhibit 11ß-hydroxysteroid dehydrogenase type 1 activity in rat adipose tissue.

Excess glucocorticoids promote visceral obesity and insulin resistance. The main regulator of intracellular glucocorticoid levels are 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive glucocorticoid into bioactive glucocorticoid such as cortisol in humans and corticosterone in rodents; therefore, the inhibition of 11ß-HSD1 has considerable therapeutic potential for metabolic diseases including obesity and diabetes. Benzofuran is a key structure in many biologically active compounds such as benzbromarone, malibatol A and (+)-liphagal. The aim of this study was to investigate the inhibitory effect of benzofuran derivatives on 11ß-HSD1 in mesenteric adipose tissue from rodents. 11ß-HSD1 activity was determined by incubation of rat mesenteric adipose tissue microsomes in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) with and without benzofuran derivatives (Compounds 1-14). The corticosterone produced was measured by HPLC. More than 40% of 11ß-HSD1 inhibition was observed in Compounds 1, 5, 7 and 8. Moreover, Compounds 7 and 8 inhibited the 11ß-HSD1 activity in adipose microsomes dose- and time-dependently, as well as in 3T3-L1 adipocytes. Compounds 7 and 8 did not inhibit 11ß-HSD type 2 (11ß-HSD2), whereas Compounds 1 and 5 inhibited 11ß-HSD2 by 18.7% and 56.3%, respectively. Further, a kinetic study revealed that Compounds 7 and 8 acted as non-competitive inhibitors of 11ß-HSD1. Ki (nmol/h/mg protein) values of Compounds 7 and 8 were 17.5 and 24.0, respectively, with IC50 (µM) of 10.2 and 25.6, respectively. These data indicate that Compounds 7 and 8 are convincing candidates for seed compounds as specific inhibitors of 11ß-HSD1 and have the potential to be developed as anti-obesity drugs.

The observation of humoral responses after influenza vaccination in patients with rheumatoid arthritis treated with Japanese oriental (kampo) medicine: an observational study.

Objective. The efficacy of influenza vaccination in patients treated with Japanese Oriental (Kampo) Medicine is unknown. The objectives of this study were to observe the efficacy of influenza vaccination in RA patients treated with Kampo. Methods. Trivalent influenza subunit vaccine was administered to 45 RA patients who had received Kampo. They were divided into 2 groups: RA patients treated without MTX ("without MTX group") and treated with MTX ("with MTX group"). Antibody titers were measured before and 4 weeks after vaccination using hemagglutination inhibition assay. Results. Geometric mean titers (GMTs) of anti-influenza antibodies significantly increased for all influenza strains. Response to the influenza vaccination in RA patients treated with Kampo was not lower than that of healthy subjects and the response in the "with MTX group" had a tendency to be higher than that in RA patients treated with MTX in the previous study. There was no significant difference in the GMT after 4 weeks between the "with MTX group" and the "without MTX group." A decreased efficacy in both seroprotection and seroconversion was not found in the "with MTX group." Conclusion. These observations may open the way for further clinical trials to establish the efficacy for the influenza vaccination in RA patients treated with Kampo.

Traditional herbal medicines (Kampo) for patients with rheumatoid arthritis receiving concomitant methotrexate: a preliminary study.

OBJECTIVE: To assess the clinical effectiveness and safety of traditional herbal medicines (THM: Kampo) used in combination with oral methotrexate (MTX) in order to control the disease activity of rheumatoid arthritis (RA) in patients whose disease remains active despite treatment with MTX. METHODS: Patients (n=13; male:female = l:12) with RA who achieved only a suboptimal response to MTX therapy (> or =6 mg/week and > or =6 months) were enrolled in this assessment. All patients were treated with Keishinieppiittokaryojutsubu (KER; decoction) according to the traditional diagnostic system. Every 3 months, joint symptoms were examined, and routine blood analysis and general serological tests including anticyclic citrullinated peptide antibody (aCCP) were performed, and then we calculated the disease activity score of 28 joints (DAS28). RESULTS: One patient withdrew from the study after 4 weeks and discontinued consultations with our department for unknown reasons. Five (41.7%) of the twelve patients were defined as responders, and seven patients (58.3%) were classified as nonresponders based on DAS28-CRP findings. On comparison between responders and nonresponders, there was no significant difference with regard to age or disease duration and the dosages of concomitant prednisolone at baseline. KER responders had lower levels of aCCP at baseline than nonresponders (mean +/- standard deviation: 329.2 +/- 113.9 U/mL vs 623.8 +/- 242.8 U/mL, respectively) (P = .046, Mann-Whitney test). Furthermore, responders to KER showed a significant decrease in the serum levels of aCCP. The annual cost for KER treatment is much less than that for other new drugs. CONCLUSION: In patients whose active RA persists despite treatment with MTX, KER in combination with MTX is safe and well tolerated and provides clinical and economic benefits. Furthermore, pretreatment serum levels of aCCP are a useful predictor of a good response to KER treatment, and a decrease in serum levels of aCCP may be an adjunctive indicator in predicting the efficacy of this kind oftreatment.

Serum levels of anti-cyclic citrullinated peptide antibodies are associated with a beneficial response to traditional herbal medicine (Kampo) in rheumatoid arthritis.

This study investigated the usefulness of biomarkers indicating beneficial response to traditional herbal medicine (THM) among patients with rheumatoid arthritis (RA). We assessed 34 RA patients who received keishinieppiittokaryojutsubu (KER), one of the representative THM. The observational term was 12 months, and we calculated the disease activity score of 28 joints every 3 months and evaluated the response to KER using European League Against Rheumatism (EULAR) response criteria. Additionally, serum levels of anti-cyclic citrullinated peptide antibody (ACPA) were measured by enzyme-linked immunosorbent assay at the baseline and after 6 and 12 months of the treatment with KER. As a result, 14 (41.2%) of the 34 patients were defined as responders, 13 as non-responders and 7 as out of assessment after 6 months, respectively. Pretreatment levels of serum ACPA were lower in KER responders than in non-responders (P = 0.042), although other univariate analysis did not show any significant differences in baseline clinical measures between the two groups. Furthermore, responders to KER showed a significant decrease in the serum levels of ACPA. These findings suggest that pretreatment serum levels of ACPA are a useful predictor of a good response to treatment with KER. Furthermore, a decrease in serum levels of ACPA may be an adjunctive indicator in predicting the efficacy of this kind of treatment.

Pueraria mirifica phytoestrogens improve dyslipidemia in postmenopausal women probably by activating estrogen receptor subtypes.

Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.

The effect of traditional herbal medicines; Uyakujunkisan on trigeminal neuralgia in an elderly patient--a case report and literature review.

This report describes the successful treatment of a 72-year-old female with refractory trigeminal neuralgia using a traditional herbal medicine, Uyakujunkisan (UJS). The case report is of a 65-year-old female who developed right-sided trigeminal neuralgia that was partially responsive to carbamazepine (CZ). The pain gradually increased in intensity and at 72 years of age she presented for herbal medicine therapy. Cranial MRI demonstrated vascular compression of the right trigeminal nerve at the cerebellopontine angle by the anterior inferior cerebellar artery. Although microvascular decompression was considered, UJS was prescribed after informed consent. After 3 weeks of treatment with UJS, dramatic improvement of symptoms permitted a decrease in CZ dose.

Insights to clinical use of serial determination in titers of cyclic citrullinated peptide autoantibodies.

Anti-cyclic citrullinated peptide (CCP) antibody is a useful marker for the diagnosis and prognosis of rheumatoid arthritis (RA). Recently, clinical significance of follow-up in anti-CCP antibody titer has been pointed out. Thus, we investigated the serial determination in anti-CCP antibodies titer in RA patients. Six patients with RA, who were followed up for longer than 5 years, were assessed in anti-CCP antibodies and radiographs (Larsen score). Anti-CCP antibodies in frozen sera were measured using ELISA. As a result, 6 patients with RA were divided into two groups: one possessed high titers without variation, and the other was without high titers. Joint damage progressed during observation in 2 out of 3 patients with high anti-CCP titers in a retrospective assessment. In contrast, the RA patient, whose anti-CCP titer decreases although it had been high titer at baseline, did not show increase in the Larsen score. These findings suggest that it might be necessary to analyze changes in anti-CCP to predict the prognosis of joint destruction.

No correlation exists between disease activity and the expression of killer-cell immunoglobulin-like receptors in patients with rheumatoid arthritis.

OBJECTIVE: The genes for killer-cell immunoglobulin-like receptors (KIRs) have been cloned and their functions and expression in patients with rheumatoid arthritis (RA) have been partially clarified. However, the correlation between their expression and disease activity has not been analyzed in patients with RA. Thus, we measured KIR expression on lymphocytes in patients with RA, and assessed the correlation between KIR expression and disease activity. PATIENTS AND METHODS: In the cross-sectional study, 15 patients (9 females and 6 males) who fulfilled the diagnostic criteria for RA were assessed. In the longitudinal study, patients who were followed-up for 3 months were assessed. CD158a/b expression on peripheral blood mononuclear cells (PBMC) of RA patients was analyzed using flow cytometry. RESULTS: No significant correlation between KIR expression and CRP, ESR, or IgM-RF was observed. There was no remarkable change in the expression of KIRs between the baseline and after 3 months. Additionally, in the 5 patients whose expression of KIRs particularly changed, the time-related changes in the expression of KIRs were independent from those of inflammation parameters and IgM-RF. CONCLUSION: There was no correlation between KIR expression and disease activity; therefore, the clinical use of KIR expression should be limited, while unnatural KIR expression may be involved in the pathogenesis of RA, but not a recruitment of chronic inflammation to induce joint damage.

Population of CD40L-expressing cells was slightly but not significantly decreased in lymphoid tissues of collagen-induced arthritic mice treated with Hochu-Ekki-To.

OBJECTIVE: To clarify the mechanism of the action of Hochu-Ekki-To (HET) on collagen-induced arthritic (CIA) mice by analyzing the CD40L-expressing cells population. METHODS: CIA was induced in male DBA/1J mice by immunization with two injections of bovine type II collagen (CII). HET or water was orally administered. The subpopulations of lymphocytes obtained from lymph nodes and spleen were detected at 3 weeks after boost using flow cytometry. RESULTS: Although the population of CD4+CD40L+ cells tended to be decreased in the HET group compared to that in control mice, there was no significant difference between the two groups. These findings were observed in lymphocytes obtained from both lymph nodes and spleen. CONCLUSION: HET suppresses the development of CIA. These effects may be partially induced via the decrease in the population of CD4+CD40L+ cells, but the role of this action is probably limited.

[Quality evaluation of magnesium oxide tablets using acid neutralization test and dissolution test].

For the purpose of quality evaluation of commercially available magnesium oxide (MgO) tablets, we studied their acid neutralization and dissolution behaviors. The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2). The dissolution amount of MgO from tablets was determined by chelatometric titration. The medium pH was periodically measured. The neutralization reaction in 750 ml of 1st fluid was markedly different between two kinds of commercial tablets. The pH of medium including Magmit tablet reached 8.9 and the dissolution rate of MgO was 81.1% after 20 min. Contrariwise, the final pH of medium including Maglax tablet was 2.5 and the dissolution rate of MgO was 77.1% after 60 min. These results indicate that the dissolution rate of MgO from tablets should be >81.1% to obtain significant acid neutralization action.

[Effects of copper supplementation on lipid profiles in elderly patients with copper deficiency].

AIM: The purpose of this study was to examine the effects of copper supplementation on lipid profiles in elderly patients with copper deficiency. METHODS: Nine long-term bed-ridden, patients (5 men and 4 women, mean age 83.3+/-8.7 years old) with severe copper deficiency, who had a serum copper of 15 microg/dL or less (normal range 70-140 microg/dL), had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Copper, ceruloplasmin, total cholesterol (TC), triacylglycerides (TG), HDL-cholesterol (HDL-C), c-reactive protein (CRP), creatinine (Cr), zinc (Zn) and albumin (Alb) in the serum were measured before, 4 weeks and 12 weeks after copper supplementation. RESULTS: Serum copper and ceruloplasmin were significantly increased at 4 weeks after copper supplementation. TG was significantly increased at 4 weeks after copper supplementation, but at 12 weeks the increase of TG was not significant. TC, HDL-C, CRP, Cr, Zn and Alb were not changed by copper supplementation. CONCLUSION: TG was transiently increased by copper supplementation in elderly patients with copper deficiency. TC and HDL-C were not changed by copper supplementation.

Reexamination of the relation between menstrual cycle and kampo diagnosis, yin-yang.

Several Chinese herbal medicine textbooks describe that a short menstrual cycle indicates "yang" status and a long cycle indicates "yin" status. However, we sometimes encounter yang patients with a long cycle or yin patients with a short cycle in daily practice. Therefore, we reviewed the relationship between yin-yang and length of menstrual cycle. A questionnaire addressing both menstrual cycle and several parameters for determining yin-yang was completed at the time of the patients' visit to the hospital. Patients were divided into yang or yin groups, and menstrual cycle was compared between the two groups. A short menstrual cycle was mostly observed in yin patients (27.42 +/- 1.73, 95% CI: 26.32-28.52, n = 12) and a long cycle was mostly observed in yang patients (31.63 +/- 3.96, 95% C.I: 29.51-33.74, n = 16). The difference in menstrual cycle between the two groups was significant (p = 0.002), and this result was entirely opposite to the traditional theory. This study identified a discrepancy between the traditional theory and the actual menstrual cycle findings in this small population. Current reexamination of the relationship between yin-yang and menstruation in a larger population is warranted.

Challenge tests and kampo medicines: case report and review of the literature.

In order to diagnose Kampo medicine-induced liver injury, a challenge test using the suspected medicine is the most reliable method of assessing the relationship between Kampo medication and liver injury. However, such a challenge test may cause severe liver injury. We examined the clinical features and safety of challenge tests conducted by a physician in a case of Kampo medicine-induced liver injury that we encountered as well as in the previous literature (six cases) in Japan. In all cases except two, one-third of the daily dose was given a few times for the challenge test (challenge dose was not described in two cases). The reaction induced by the challenge peaked 1-3 days after challenge. Mild eosinophilia (6%) was observed in two cases. All liver injuries induced by challenge cleared within 2 weeks, and neither severe nor fatal liver injury was observed. In conclusion, a challenge with a small dose of Kampo medicine conducted in our case and in the previous literature induced mild and reversible liver injury. The safety and availability of challenge with a small dose of Kampo medicine should be further examined in a larger population with Kampo medicine-induced liver injury.

Herbal medicine and false-positive results on lymphocyte transformation test.

In vitro mitogenic activity of 16 herbs and 3 Kampo (herbal medicine) formulae have been reported in experimental studies. It is not known how many herbs and Kampo formulae in total have mitogenic activity. Lymphocyte transformation test (LTT) is generally utilized to diagnose drug-induced liver injury. In LTT, mitogenic activity is assessed by measuring 3H-thymidine incorporation. The objective of the present study was to determine which herbs and which Kampo formulae caused false-positivity on LTT. We examined 2496 summaries of all admission records from 1979 to 1999 in our department. We selected patients in whom liver injuries were diagnosed as definitely unrelated to Kampo medication. In these patients, LTT was performed for some herbs contained in the suspect Kampo medicines, resulting in positive LTT for 17 herbs: Evodiae Fructus (Goshuyu), Zizyphi Fructus (Taiso), Ginseng Radix (Ninjin), Zingiberis Rhizoma (Shokyo), Hoelen (Bukuryo), Aconiti Tuber (Bushi), Angelicae Radix (Toki), Cnidii Rhizoma (Senkyu), Rehmanniae Radix (Jio), Ephedrae Herba (Mao), Anemarrhenae Rhizoma (Chimo), Cinnamomi Cortex (Keihi), Bupleuri Radix (Saiko), Artemisiae Capillari Spica (Inchinko), Persicae Semen (Tonin), Moutan Cortex (Botanpi) and Paeoniae Radix (Shakuyaku). These results were considered false-positive, because the results were observed in the "definitely unrelated" patients. Mitogenic activity inherent to some herbs and Kampo formulae may sometimes cause false-positivity on LTT in clinical situations. These examples suggest that LTT for Kampo formulae may be unreliable as a diagnostic method for drug-induced liver injury.

Rhubarb use in patients treated with Kampo medicines--a risk for gastric cancer?

In vitro mutagenic effects have been reported for ingredients contained in rhubarb. Therefore, rhubarb (Rhei Rhizoma) as an anthranoid laxative could be associated with a risk of developing gastric cancer as well as colorectal cancer. We are not aware of any reports that have examined the relationship between the use of rhubarb and the development of gastric cancer. During the period between 1979 and 1999, we treated 14,616 patients using various Kampo medicines, which sometimes contained rhubarb. In the present study, we determined whether patients, diagnosed with gastric cancer during the period between 1979 and 1999, had been administered rhubarb before the development of gastric cancer. Among the 10 enrolled patients, only 2 patients had been administered rhubarb before the development of gastric carcinoma. The other 8 patients had never received rhubarb before the development of gastric carcinoma. Rhubarb use may have little connection with the development of gastric cancer in practice, even if some ingredients in rhubarb have shown carcinogenic activity in experimental studies.

[Relationships among urine pH, serum uric acid and pyuria in hospitalized elderly patients].

To identify risk factors of urinary tract infection (UTI) in geriatric patients, the levels of serum uric acid, serum creatinine, and urine pH were compared between pyuria-positive and -negative patients in a geriatric ward. The level of serum uric acid was higher with lower urine pH level in the pyuria-negative patients than in positive patients. The level of serum creatinine was relatively higher in the pyuria-negative patients than in the positive patients. Even after matching for serum creatinine, serum uric acid was significantly higher in the pyuria-negative male patients. The results in the present study proposed an interesting hypothesis about backgrounds for UTI in geriatric patients. The relationships among serum uric acid, serum creatinine, urine pH, and pyuria should be examined further in a larger population and in experimental studies.

[Opinions of doctors and nurses about appropriate medical treatment for terminally ill geriatric patients].

We investigated the opinions of medical doctors and nursing staff about desirable medical treatment for terminally ill geriatric patients. The purpose of the present study is: 1) to examine the recent opinion of doctors and nurses, 2) to examine discrepancies of opinions between doctors and nurses on treatment for terminal geriatric patients. Doctors and nurses working in long-term care wards in four hospitals were enrolled. They were asked to fill in a questionnaire which asked about desirable medical treatments for a typical bedridden terminally ill geriatric patient. The difference of answers between doctors and nurses were analyzed. The most common opinion of the 18 doctors and 84 nurses were as follows: 1) for the treatment of relapsing pneumonia, they would perform oxygenation, antibiotic injections, and continuous intravenous infusion during the period of discontinuation of enteral nutrition, 2) for the treatment of relapsing urinary tract infection, they would catheterize patients for a brief period and would irrigate the bladder, and would perform antibiotics injection, 3) for chronic anemia, they would perform iron replacement, 4) for decubitus ulcer, they would treat conventionally, and 5) at the final stage just before death, they would avoid special therapy for shock after obtaining informed consent from patient's family. To most questions, the proportion of each answer was almost identical between doctors and nurses; however, there were discrepancies concerning "way of nutrition in patients with relapsing pneumonia" and "irrigation of the urinary bladder" (p = 0.0544 and 0.0531, respectively). We expect that the present study will activate a discussion of what constitutes appropriate medical treatment for terminally ill geriatric patients.

Investigation of clinical characteristics as predictive factors for the humoral immune response to the influenza vaccine in patients with rheumatoid arthritis.

The objective of this observational study is to determine characteristics as predictive factors for the humoral immune response to the influenza vaccine in patients with rheumatoid arthritis (RA). Fifty-seven RA patients who visited our department between 2011 and 2012 were recruited for the present study. The anti-influenza antibody titers of a trivalent influenza subunit vaccine (A/California/7/2009 (H1N1)-like strain (A/H1N1 strain), A/Victoria/210/2009 (H3N2)-like strain (A/H3N2 strain), and B/Brisbane/60/2008-like strain (B strain)) were measured at baseline and 4 weeks after the vaccination using the hemagglutination inhibition assay. Associations between the immune response to the influenza vaccine and clinical characteristics such as background, clinical parameters, and "having treatments or not" were examined to determine predictive factors for the immune response to the influenza vaccine. The titers of the three strains were significantly increased in all RA patients after the influenza vaccination. Concerning predictive factors of the immune response, no significant differences were observed in background (age and sex) or clinical parameters (peripheral lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, matrix metalloproteinase-3, and disease activity score-28). No significant differences were observed in the titers of anti-influenza antibodies between the treatment (methotrexate, prednisolone, salazosulfapyridine, or tacrolimus) and no-treatment groups. In contrast, there was a significant difference in A/H3N2 strain between the patients with biologics and without biologics. The only factor that affected anti-influenza antibody titers was "having biologics or not"; therefore, the immune response to the influenza vaccine may not be predicted from the viewpoints of background and clinical parameters.