Understanding the Differences in Strategic Alliance Formation in the Indian and Chinese Pharmaceutical Industry

By using data on Indian and Chinese pharmaceutical companies, before and after the domestic implementation of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPs), this study seeks to understand the role of the institutional theory in the formation of strategic alliances. Four structural dimensions of strategic alliances formation are identified as economic distance, the number of alliance participants, cross-national and partner diversity across different alliance types- marketing, manufacturing, licensing, retail and wholesale services, R&D, health and medical services, and others. Some alliances from both countries are multi-type which are categorized as different variables. The trend analysis reveals that TRIPS does not appear to be impactful for either country which aligns with its staggered domestic implementation in both countries. Through an analysis involving the Fisher Exact test on a dataset of 307 strategic alliances, this study finds that China had a statistically significant greater number of alliances with heterogeneous partners, partners from different industries, manufacturing alliances, all single type alliances (alliances that had only one type of motivation), and all alliances as compared to India. Furthermore, India demonstrated a statistically significant preference for multipurpose alliances revealing a broader trend of China engaging in more single motivation alliances in comparison to India’s fewer multipurpose strategic alliances with respect to the pharmaceutical industry

INTERLEUKIN-17INHIBITION WITH SECUKINUMAB IMPROVES SUDOMOTOR DYSFUNCTION IN PSORIATIC ARTHRITIS

Psoriatic arthritis (PsA) is a relapsing inflammatory disease, most commonly a seronegative oligoarthritis found in patients with psoriasis, characterized by the absence of rheumatoid factor in serum, with differentiating features of distal joint involvement and in extreme cases of arthritis mutilans (which is a destructive form of PsA). Cardiovascular autonomic and peripheral sympathetic neuropathy occurs in PsA. However, there is no specific treatment recommendation for autonomic neuropathy (AN) in psoriatic diseases. Secukinumab, a recently approved therapeutic advancement for psoriasis and psoriatic arthritis, is an immunoglobulin G (IgG) 1k fully monoclonal antibody that selectively inhibits the effector function of interleukin (IL)-17A. Its effect on sudomotor dysfunction in PsA has not yet been reported. This is the first reported observation of improvement in peripheral sympathetic autonomic neuropathy with secukinumab in PsA. We report a case of a 52-year-old male with PsA on methotrexate 15 mg/week with severe disease activity treated with the addition of subcutaneous secukinumab 150 mg once a week for 5 w followed by once a month dose. We found significant improvement in sudomotor dysfunction after 4 and 8 w of treatment

OSTEOPOROTIC FRACTURE RISK IN RHEUMATOID ARTHRITIS

Objective: Osteoporosis is an extra-articular complication of rheumatoid arthritis (RA) with increased risk of fractures. FRAX is an online tool for assessing risk of osteoporotic fracture. However, the relationship between the FRAX score and disease specific risk factors has not yet been investigated in RA. Hence, we assessed 10-year fracture risk using FRAX and its relationship with disease activity score, inflammation and disease duration in RA.Methods: 50 RA patients enrolled and recruited consecutively in a special camp organized for RA patients on the occasion of World Osteoporosis Day, 2016to estimate the osteoporotic fracture risk from Rheumatology clinic. Predicted 10-year risk of hip fracture and major osteoporotic fracture (MOF) by FRAX score without information on bone mineral density (BMD). Inflammatory disease activity measures included disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured. FRAX score also estimated in 40 age and sex matched healthy controls.Results: FRAX estimated significantly enhanced fracture risk in active RA, both for MOF (13.34±1.26%) and hip fracture (6.84±1.03%) as compared to controls for MOF (5.46±0.95%) and hip fracture (1.97±0.49%). In RA patients, MOF and hip fracture risk correlated with DAS28 and disease duration and MOF risk correlated with ESR and CRP.Conclusion: Active RA patients, even in the absence of BMD have an increased FRAX score indicating an enhanced 10-year probability of MOF and hip fracture. Long disease duration, high disease activity and an elevated ESR and CRP are potential disease specific risk factors for osteoporotic fractures in RA

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Intrathecal Injection of Spironolactone Attenuates Radicular Pain by Inhibition of Spinal Microglia Activation in a Rat Model

Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation.Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn't affected.These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects