The DNA double helix structure proposed in 1953 theorized that the nucleotide sequence carries the genetic information that has a decisive influence on the development of cellular and molecular biology. From that revelation, biotechnology centered on genetic recombination technology has generated many innovative biopharmaceuticals, treating a wide range of diseases.

  The size of the Japanese biopharmaceutical market reached 1.4 trillion yen in 2017, 61% of which is accounted for by antibody drugs. It is expected that biopharmaceuticals will continue to show nearly double the market growth rate of small molecule therapies. What is more, a market for new modalities such as nucleic acid medicines, cell therapies and gene therapies is also developing and evolving. The development of biopharmaceutical products by designing products and formulations that combine innovative technologies across various research fields is the key to success in this market.

  Since 1983, I have engaged in the research and development of biopharmaceuticals. I have discovered drugs for granulocyte colony stimulating factor, and humanized anti-IL-6 receptor antibody. I, as it were, have walked with the history of biopharmaceutical’s.

  This article reviews a half century of biopharmaceuticals and outlines the prospects of biopharmaceuticals that will contribute to innovative medical treatments in the future.

  A 60-year-old woman was diagnosed with psoriasis vulgaris in 2007. Although she received antiallergic drug and ointment at the clinic, her skin condition did not improve, so administration of etretinate was started at the Department of Dermatology in 2009. While skin disease improved a little with etretinate, she still had multiple tender joints including knees, elbows and interphalangeal joints in 2010. She came to Department of Rheumatology in 2011. We diagnosed psoriatic arthritis（PsA）. It was difficult to treat with biologics due to economic problems, and we first treated with salazosulfapyridine（SASP）and prednisolone（PSL）. In spite of the treatment, joint space narrowing of the hip became aggravated, so we switched to infliximab（IFX）from January 2016. We started combined use of methotrexate（MTX） from January 2017, but discontinued due to leukopenia in 3 months. As right hip joint destruction progressed regardless of the treatment, we planned to perform total hip arthroplasty.

  While the main symptoms of PsA are psoriasis, peripheral arthritis, spinal lesions, enthesitis and dactylitis, joint destruction of large joints such as the hip is rare. Hip lesion was reported to occur within 1 year after the onset of PsA and was difficult to stop worsening in spite of the use of biologics. In addition, outcomes after THA would be poor, so we should carefully observe and start appropriate therapies at the appropriate time.

［Objectives］In Japan, infliximab（IFX）and etanercept（ETN）were applied to RA treatment in 2003 and 2005, respectively. RA treatment with adalimumab（ADA）had been conducted in clinical trials since 2003. In this study, we evaluated the retention rate of these tumor necrosis factor（TNF）inhibitors for over 10 years.

［Materials and Methods］RA patients who had started the treatment with IFX, ETN, or ADA before 2007 in Matsubara Mayflower Hospital and were observed for over 10 years were included in this study. IFX was used for 111 patients with RA, and 95 of them were observed for over 10 years（IFX group）. 95 of 119 RA patients treated with ETN（ETN group）and 24 of 27 RA patients treated with ADA（ADA group）were included in this study. Kaplan-Meier analysis was applied to determine the differences in the retention rates of these TNF inhibitors.

［Results］Kaplan-Meier analysis showed no statistically significant difference in the retention rates of these biologics. The retention rates for 12 years of IFX, ETN and ADA were 10.5%, 22.1% and 8.3%, respectively. DAS 28（CRP）at the start of IFX and the age at onset were correlated negatively with the retention rate of IFX and ETN, respectively. Discontinuation rate due to remission in ADA group was the highest.

［Conclusions］In this study, there was no statistically significant difference in the retention rates of 3 TNF inhibitors. The retention rate for 12 years of ETN was the highest and that of ADA was the lowest.

  A man in his sixties was referred to our hospital with numbness in the extremities and presented with systemic lymph node swelling including prominent immunoglobulin（Ig）G4-positive cell infiltration as well as an elevated serum IgG4 level. He lacked subjective sicca symptoms but was positive for anti-SS-B antibody. Periductal focal mononuclear cell infiltration in labial salivary gland biopsy specimen led to the diagnosis of Sjögren’s syndrome. This is the first case of a patient with anti-SS-A antibody-negative/anti-SS-B antibody-positive Sjögren’s syndrome concomitant with increased serum and lymph node IgG4.

  RA patients in a disaster are not in an urgent situation, but require a lot of support to evacuate. In this paper, I describe appropriate nursing support methods in case of encountering RA patients in areas affected by disaster. Specifically, I will describe the necessity to prepare RA patients for evacuation, drug problems held by RA patients immediately after disaster, issues faced by RA patients when living in evacuation centers, necessary support, consideration of transfer to welfare evacuation centers, and the problems that RA patients have in the long term when a disaster occurs.

  Immediately after the occurrence of the earthquake in Kumamoto on 14th April of 2016, Hyogo Pharmaceutical Society, Disaster / Public Health Division dispatched disaster assistant pharmacists to Mashiki Town and South Aso village of Kumamoto Prefecture. Before the occurrence of the earthquake, we had already registered 246 pharmacists who had completed disaster-oriented training. Therefore, they could respond to the disaster with common awareness as disaster-support pharmacists.

  Because JMAT Hyogo was in charge of the Health and Welfare Center in Mashiki Town, we were requested to serve as the General Headquarters Team with the functions of dispensing the facilities and a mobile pharmacy（Mobile Pharmacy Vehicle）.

  In response to information of a shortage of chips for blood glucose measurement at evacuation centers from a volunteer nurse, we investigated the needs of evacuees. Based on this, we immediately informed the results to Hyogo Prefecture Medical Association and delivered supplies in a warehouse according to the need of evacuees.

  Because of the importance of interdisciplinary collaboration, we need to make preparations and conduct training under normal circumstances.

Purpose

To report the role of rehabilitation experts for the support of disaster rehabilitation by referring to past activities.

Method

Many rehabilitation-related organizations worked together to support the disaster victims of the Great East Japan Earthquake that occurred in 2011. The Japan Disaster Rehabilitation Assistance Team（JRAT）was established to keep up with the support activity of disaster rehabilitation due to the devastating large scale disaster. JRAT established local support organizations in each prefecture and held training sessions targeting rehabilitation experts, so it is possible to for JRAT to manage the supporting activity of disaster rehabilitation throughout Japan.

Result

The primary support targets of JRAT are children, woman and aged people patients（CWAP）who need special care. JRAT considers that increasing CWAP activity can prevent the occurrence of new diseases such as disuse syndrome and economy class syndrome at the time of the Kumamoto earthquakes. Therefore, JRAT proposed environmental improvement of evacuation centers, taught frail elderly people how to stand up from the floor, and promoted activities such as walking exercise and lower limb exercise to improve their activities.

Conclusion

Disaster rehabilitation assistance by rehabilitation professionals is now well organized. JRAT keeps developing human resources by providing disaster training and we hope to be a very useful organization for disaster victims when devastating disasters occur.

【Objective】We have designed a study addressing concerns raised specifically regarding conditions, clinical bias, number of study subjects and approach of identification of biomarkers, in order to identify predictive biomarkers of TNF inhibitors（TNFi）using patients’ blood expression profiles.

【Patients and Methods】All study subjects（n=219）were bDMARDs treatment naïve and considered for co-administration of methotrexate（MTX）and TNFi. It represented the biggest cohort（n=219）ever studied using genome-wide gene expression profiles. To obtain a robust gene panel, we have referred to 6 disease activity criteria（DAS28, CDAI, EULAR, ACR, SJC28 and CRP）to determine treatment response. We designated 2 thresholds for each criterion and this generated 12 pairwise comparisons. Baseline clinical information was matched, and genes that were common in at least 4 out of 12 comparisons were extracted.

【Results】Thirty four genes were shortlisted. Ribosome-related genes were highly expressed in RES while type I interferon related-genes were found to be highly expressed in NRES. A combination of predictive biomarkers and baseline clinical information has an accuracy of 64.5-83.6%, significantly better than baseline clinical information alone.

【Conclusion】Accuracy of prediction improves when combining blood-based predictive factors in this study and clinical data. Reproducibility in a prospective trial is warranted, also to demonstrate causal or consequential relationship between functions of these genes and disease activity of RA.