Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin.
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PMID:Rioprostil prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dogs and arthritic rats. 310 26

Arthrotec (Searle) is a new concept in NSAID therapy that provides powerful anti-inflammatory efficacy with enhanced upper GI safety. Arthrotec comprises an enteric-coated core of diclofenac sodium (50 mg) surrounded by a mantle of misoprostol (200 mcg). Two multicentre trials evaluated the efficacy of Arthrotec in rheumatoid arthritis (RA) and osteoarthritis (OA) patients who were randomised to receive either Arthrotec or diclofenac. The results of all arthritis assessments showed Arthrotec to be as effective as diclofenac in treating the signs and symptoms of RA and OA. Two endoscopic studies compared the antiarthritic efficacy and gastroduodenal safety of Arthrotec and diclofenac. In a 12-week study of RA patients, the antiarthritic efficacy of Arthrotec was equivalent to diclofenac; in addition, 60% fewer patients taking Arthrotec experienced ulcers than did those taking diclofenac (4.4% Arthrotec vs 11.1% diclofenac: P = 0.034). In a 4-week study of OA patients, Arthrotec's efficacy was equivalent to that of diclofenac and the Arthrotec group developed no ulcers, while 3.6% of the diclofenac group had ulcers (P = 0.015). In a trial conducted to compare the efficacy and upper gastroduodenal safety of Arthrotec with those of piroxicam and naproxen, patients with OA received either Arthrotec BID piroxicam 10 mg BID, or naproxen 375 BID for 4 weeks. Arthritis assessments showed Arthrotec to be at least as effective as piroxicam and naproxen in treating OA. Post-treatment endoscopy data indicated that gastroduodenal ulcers developed in 1.5% of patients receiving Arthrotec, 10.3% of patients receiving piroxicam, and 8.6% patients in the naproxen group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arthrotec: a therapeutic option in the management of arthritis. 782 36

Research strongly indicates that increased expression of the isoenzyme cyclooxygenase-2 (COX-2) is responsible for elevated production of prostaglandins in inflamed joint tissues and is involved in the mediation of pain. In contrast, COX-1 is a constitutively produced isoenzyme that is involved in the synthesis of eicosanoids that have important homeostatic functions, for example, in the gastric mucosa and platelets. This new knowledge led to the development of drugs that are highly specific inhibitors of COX-2 while not inhibiting COX-1 at maximally efficacious dosages. The first COX-2 specific agent approved for clinical use in the United States was celecoxib. Large multicenter trials have shown that celecoxib at dosages of 100 mg BID and 200 mg BID is as effective as naproxen 500 mg BID in patients with osteoarthritis of the knee or hip. Another large multicenter trial also demonstrated that celecoxib 200 mg BTD and 400 mg BID is as effective as naproxen 500 mg BID in patients with rheumatoid arthritis (RA). A comparative trial showed that celecoxib 200 mg BID is as effective as diclofenac SR 75 mg BID in patients with RA. The potential of COX-2 specific inhibitors to provide antiinflammatory and analgesic efficacy equivalent to that of conventional nonsteroidal antiinflammatory drugs without the adverse gastrointestinal mucosal and platelet effects associated with nonspecific COX inhibitors promises to revolutionize the clinical care of arthritis patients.
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PMID:Antiinflammatory and analgesic efficacy of COX-2 specific inhibition: from investigational trials to clinical experience. 1103 98

A phase I study of fixed-dose 5-fluorouracil (FU) and leucovorin (LCV), with excalating doses of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib, was conducted in 16 patients with advanced colorectal adenocarcinoma. At doses typically used to treat arthritis patients (100-200 mg po BID), celecoxib did not increase toxicities expected from the chemotherapy alone. 5-FU and leucovorin did not affect COX-2 inhibition by celecoxib. Preliminary data suggest it is safe to combine celecoxib with standard chemotherapeutic agents, in treatment of patients with colorectal cancer.
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PMID:A phase I study of 5-fluorouracil, leucovorin, and celecoxib in patients with incurable colorectal cancer. 1578 23

A critical piece in the translation of preclinical studies to clinical trials is the determination of dosing regimens that allow maximum therapeutic benefit with minimum toxicity. The preclinical pharmacokinetic (PK)/pharmacodynamic (PD) profile of tofacitinib, an oral Janus kinase (JAK) inhibitor, in a mouse collagen-induced arthritis (mCIA) model was compared with clinical PK/PD data from patients with rheumatoid arthritis (RA). Preclinical evaluations included target modulation and PK/PD modeling based on continuous subcutaneous infusion or oral once- or twice-daily (BID) dosing paradigms in mice. The human PK/PD profile was obtained from pooled data from four phase 2 studies in patients with RA, and maximal effect models were used to evaluate efficacy after 12 weeks of tofacitinib treatment (1-15 mg BID). In mCIA, the main driver of efficacy was inhibition of cytokine receptor signaling mediated by JAK1 heterodimers, but not JAK2 homodimers, and continuous daily inhibition was not required to maintain efficacy. Projected efficacy could be predicted from total daily exposure irrespective of the oral dosing paradigm, with a total steady-state plasma concentration achieving 50% of the maximal response (Cave50) of ~100 nM. Tofacitinib potency (ED50) in clinical studies was ~3.5 mg BID (90% confidence interval: 2.3, 5.5) or total Cave50 of ~40 nM, derived using Disease Activity Scores from patients with RA. The collective clinical and preclinical data indicated the importance of Cave as a driver of efficacy, rather than maximum or minimum plasma concentration (Cmax or Cmin), where Cave50 values were within ~2-fold of each other.
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PMID:Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis. 2421 41

Spondyloarthrites (SPA) represent a group of heterogenous rheumatic diseases (ankylosing spondylitis/SA, psoriatic arthritis/PsA, reactive arthritis/ReA, spondyloarthritis in bowel inflammatory diseases/BID, undifferentiated spondyloarthritis/undif SpA) with distinct clinical features and common genetic predisposition (HLA-B27). SpA may also affect other organs, ocular involvement, represented by uveitis and conjunctivitis, being one of the most important extraskeletal manifestations. Pathogenic mechanisms of ocular involment in SpA are not entirely known; nevertheless, the inflammatory process which characterizes the main rheumatic diseases seems to be responsible for this extraskeletal manifestation. SpA treatment targeted at clinical remission has a favourable effect not only on articular but also on ocular involvement. The discovery of new pathogenic mechanisms of both rheumatic and eye disease in SpA have contributed to identification of new pathogenic therapies. The interdisciplinary team work of rheumatologists and ophtalmologists have prove essential for the management of SpA patients with ocular manifestations.
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PMID:[Ocular involvement in spondylarthritis--new mechanisms, new therapies]. 2514 20