Bito T.,Kobe University |
Nishikawa R.,Kobe University |
Hatakeyama M.,Kobe University |
Kikusawa A.,Kobe University |
And 10 more authors.
British Journal of Dermatology | Year: 2014
Background Current treatment with biologics has produced dramatic therapeutic effects in patients with psoriasis, although these agents occasionally decrease in efficacy. One of the main factors responsible for this attenuation is attributed to the development of antidrug antibodies (ADAs). Objectives To analyse the relationship between serum drug concentrations, the presence of ADAs and treatment efficacy of adalimumab and infliximab, and to determine the optimal use of these biologics. Methods This was a 1-year prospective study in the dermatology departments of Kobe University Hospital and collaborating hospitals. All patients starting a regimen of adalimumab and infliximab for psoriasis were included. We measured the serum concentration of the drugs and titres of antibodies to adalimumab and infliximab, as well as the Psoriasis Area and Severity Index scores at weeks 0, 4, 12, 24 and 48 during the first year of treatment. Results We observed a 50% positive rate of ADAs to adalimumab, and a 41% positive rate of ADAs to infliximab. The titres of ADAs showed a wide range from low to high titres. In the high-titre groups, the patients exhibited a decreased clinical response, and demonstrated a negative correlation between titre and clinical response. However, an equivalent therapeutic effect was observed between the low-titre group and the group with no antibodies detected for adalimumab. For infliximab, the patients with ADAs showed decreased clinical response. An apparent negative correlation between antibody production and reduced clinical response was observed. Conclusions Two biologics, adalimumab and infliximab, showed different therapeutic behaviour. The measurement of ADAs and drug concentrations has important implications for treatment with biologics. What's already known about this topic? High frequent production of antidrug antibodies (ADAs) has been observed in patients treated with biologics, and the production has caused impairment of treatment efficacy. What does this study add? The optimal use of the biologics should be determined by the measurement of ADAs and each drug concentration in each patient because the standard protocol may not uniformly fit all patients. © 2013 British Association of Dermatologists.
PubMed | Rokko Island Hospital, Kinki Central Hospital, Kitatsuji Clinic, Kohnan Hospital and 24 more.
Type: Journal Article | Journal: International journal of clinical oncology | Year: 2016
Endocrine treatment-related adverse events have a strong impact on patients quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side effect of aromatase inhibitors, evaluation of associated risk factors may yield significant findings.A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers for assessment of patient-reported outcomes (PROs) in this prospective cohort study (SAVS-JP, UMIN000002455). Patients completed the self-report questionnaire at baseline and after 3, 6, 9, and 12 months of treatment for evaluation of frequency of treatment-related joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness).We obtained PROs from 362 patients (92.6 %) at baseline and at one or more subsequent points. New or worsening from baseline of joint symptoms were reported by 260 patients (71.8 %). More than 90 % of the symptoms were mild or moderate and nearly 80 % had occurred by 6 months. Multivariate analysis showed that a short time span after menopause [odds ratio (OR) 0.95, 95 % confidence interval (CI) 0.90-0.99; P = 0.02] and adjuvant chemotherapy (OR 2.29, 95 % CI 1.06-4.95; P = 0.03) were significant independent risk factors for joint symptoms. No significant relationships between body mass index (BMI) and joint symptoms were identified. Eighteen patients discontinued treatment during the 1st year and eight of them reported joint symptoms.Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.
Body mass index and menopausal disorders during menopause affect vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes
PubMed | Rokko Island Hospital, Kinki Central Hospital, Kitatsuji Clinic, Kohnan Hospital and 25 more.
Type: | Journal: Breast cancer (Tokyo, Japan) | Year: 2016
Adverse events related to endocrine therapies have a major impact not only on patients quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs).For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they had become worse than at baseline.Hot flashes, night sweats, and cold sweats at baseline were reported by 20.5, 15.1, and 8.2% of the patients, respectively, and new appearance or worsening of symptoms in comparison with baseline by 38.4, 29.3, and 28.7%, respectively. About 80% of newly occurring symptoms were Grade 1, and less than 5% were Grade 3. Vasomotor symptoms were reported by 201 out of 362 patients (55.5%) during the first year and the mean time to onset was 5.6months. Patients with vasomotor symptoms were significantly younger (mean 62.8years, range 38-86 vs 64.7years, range 37-84; p=0.02), had higher body mass index (BMI) (23.4kg/mHigh BMI and experiencing menopausal disorders at menopause were found to be significantly associated with the occurrence of vasomotor symptoms. These findings are expected to prove useful for the management of postmenopausal Japanese women treated with aromatase inhibitors.
PubMed | Kawasaki Municipal Ida Hospital, Kinki Chuo Chest Medical Center, Komaki Municipal Hospital, Kinki Central Hospital and 6 more.
Type: Journal Article | Journal: Journal of palliative medicine | Year: 2016
Respiratory symptoms, dyspnea, cough, and death rattle, are common and distressing in advanced cancer patients. Palliation of respiratory symptoms is important to improve quality of life in cancer patients and their families/caregivers. Currently published clinical guidelines for the management of these respiratory symptoms in cancer patients did not cover the topics comprehensively or were not based on formal process for the development of clinical guidelines.The Japanese Society for Palliative Medicine (JSPM) decided to develop comprehensive clinical guidelines for the management of respiratory symptoms in cancer patients following the formal guideline developing process.This article provides a summary of the recommendations with the rationales, as well as a short summary of the developing process, of the JSPM respiratory symptom management guidelines. We established 26 recommendations and all recommendations are based on the best available evidences and expert consensus.More future clinical researches and continuous guideline updates are required to improve the quality of respiratory symptom management in cancer patients.
Shimatsu A.,National Hospital Organization Kyoto Medical Center |
Teramoto A.,Nippon Medical School |
Teramoto A.,Tokyo Rosai Hospital |
Hizuka N.,Tokyo Women's Medical University |
And 3 more authors.
Endocrine Journal | Year: 2013
The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism. © The Japan Endocrine Society.
Imashuku S.,Takasago seibu Hospital |
Kudo N.,Takasago seibu Hospital |
Kubo K.,Takasago seibu Hospital |
Takahashi N.,Hyogo Prefectural Kakogawa Medical Center |
Tohyama K.,Kawasaki Medical School
International Journal of Hematology | Year: 2012
When elderly patients present with persistent thrombocytosis, myeloproliferative disease, iron-deficiency anemia or post-splenectomy status are suspected along with autoimmune diseases. Reported here are the cases of two elderly patients with persistent thrombocytosis due to hyposplenia, which is very rarely diagnosed in old age. Case 1 was a 72-year-old man whose thrombocytosis was due to non-familial type isolated congenital asplenia. Case 2 was a 74-year-old man whose thrombocytosis was caused by an atrophied spleen resulting from perforated stomach ulcer-related panperitonitis that had been treated 20 years previously. Both patients had thrombocyte counts exceeding >500,000/μl in association with small vestigial spleen tissue on a computed tomography scan and positive Howell-Jolly bodies on the blood smear. A correct diagnosis is essential for the management of persistent thrombocytosis. © The Japanese Society of Hematology 2012.
PubMed | Aichi Gakuin University, Kobe University, Hyogo Prefectural Kakogawa Medical Center, Konan Kosei Hospital and 2 more.
Type: Journal Article | Journal: Journal of clinical and translational hepatology | Year: 2016
Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease.Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines.All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure.All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD.