Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19097399 [Still disease in adult: a Senegalese case report]. 2007 INTRODUCTION: The adult Still's disease is a systematic disease rarely reported in the black Africans. We are reporting a case characterized among other difficulties by its diagnostic difficulties. OBSERVATION: It is about a 29 years old black Senegalese woman patient, without particular antecedents, which presented a systematic chronic syndrome composed of a pharyngitis, a polyarthritis and general symptoms (fever, chills, sweats, change of the general state), a cutaneous eruption, a polyadenopathy, a hepatosplenomegaly. The biological analyses showed among others, an inflammatory syndrome (VS at 115 mm in the 1st hour, CRP at 100 mg/L, WBC at 10,400/mm3 with neutrophilia), a hyperferritinemia in 643 ng/l with collapse of the glycosylated ferritin at 13% (N between 60 in 80%). After elimination of any autoimmune or neoplastic suppurative infectious pathology in the decline of a check up as exhaustive as possible, the diagnosis of a Still disease in adult had been retained. Their was improvement under the combination of prednisone and methotrexate. CONCLUSION: Although it is exceptional in black African, this pathology shall be however part of the differential diagnoses of any unexplained systematic sign. The dosage of the ferritinemia and its glycosylated fraction as well as the resort to the criteria of Yamaguchi and Fautrel's classification of Still Disease in Adult shall allow to establish more prematurely the diagnosis of this potentially severe affection.
17538564 Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis 2007 Jun Adult-onset Still's disease is a rare systemic inflammatory disease of unknown etiology, characterized by daily high, spiking fevers, evanescent rash, and arthritis. There is no single diagnostic test for adult-onset Still's disease; rather, the diagnosis is based on clinical criteria and necessitates the exclusion of infectious, neoplastic, and other 'autoimmune' diseases. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon-gamma, tumor necrosis factor, and macrophage colony-stimulating factor are elevated in patients with adult-onset Still's disease and are thought to have a major role in the pathogenesis of the disease. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold, azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors. Recent advances in basic immunology have enhanced our ability to hinder the pathogenic mechanisms associated with adult-onset Still's disease and have led to a paradigm shift where targeted treatments have an increasingly important role.
17827869 Tranilast suppresses the disease development of the adjuvant- and streptococcal cell wall- 2007 Sep This study explores the effects of the anti-allergic and anti-fibrotic agent tranilast on adjuvant- and streptococcal cell wall-induced arthritis in rats, animal models of rheumatoid arthritis in humans. Tranilast (150 or 300 mg/kg, twice daily) or vehicle only was administered orally to the two arthritis models, from 17 days before sensitization. As a comparative control, methotrexate (0.1 mg/kg, once daily) was given to another group. Tranilast suppressed the increase in foot volumes, paw thicknesses, clinical scores, and histopathological scores of the ankle joints in both models dose-dependently. In addition, the fibrosis indices of the ankles were dramatically decreased by tranilast in both of the models. Compared to the effects of methotrexate, tranilast seemed to work more effectively in the streptococcal cell wall-induced arthritis model than in the adjuvant-induced arthritis model. From these observations, it can be concluded that tranilast suppresses the development of arthritis in multiple models and is potentially a novel therapeutic agent for human rheumatoid arthritis.
19028363 Adult-onset Still disease. 2008 Oct Adult-onset Still disease (AOSD) is an uncommon inflammatory condition of unknown origin typically characterized by four main (cardinal) symptoms: spiking fever > or =39 degrees C, arthralgia or arthritis, skin rash and hyperleucocytosis (> or =10,000 cells/mm3) with neutrophils > or =80%. As many other manifestations are possible, diagnosis is potentially challenging. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. The disease evolution of AOSD can be monocyclic, polycyclic or chronic. In chronic disease, joint involvement is often predominant and erosions are noted in one-third of patients. No prognostic factors have been identified to date. Therapeutic strategies are from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy with agents blocking interleukin-1 (anakinra) and then those blocking interleukin-6 (tocilizumab) seem the most promising.
17683708 [Adult onset Still's disease: review of 26 cases]. 2007 Jul 14 BACKGROUND AND OBJECTIVE: We intended to describe the clinical characteristics, treatment and evolution of 26 patients with adult onset Still's disease. PATIENTS AND METHOD: This was a retrospective study (1984-2004). The clinical records of patients with adult onset Still's disease were reviewed. RESULTS: Twenty six patients were included. Most frequent clinical characteristics were: fever (100%), arthritis (81%), rash (92%) sore throat (92%) and lymphadenopathy (42%). Aspirin controlled the disease in 27% of patients, prednisone was needed in 70% and methotrexate was added in 50% cases. A monocyclic course was seen in 54% and polycyclic in 46% patients. CONCLUSIONS: The clinical characteristics were similar to previous series. A febrile polyarthritis was the most frequent presentation form. A polycyclic course was found in 58% of cases and it seems to be associated with poor prognosis and need for aggressive treatment.
16365690 A multicenter study of patients with adult-onset Still's disease compared with systemic ju 2006 Sep Adult-onset Still's disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.
18592135 Steroid-refractory severe hepatic failure in adult onset Still's disease responding to cyc 2008 Nov We report two Japanese women with severe hepatic dysfunction and adult onset Still's disease. A 51-year-old woman had been diagnosed with adult onset Still's disease 3 years earlier. She relapsed while on maintenance therapy with prednisolone and methotrexate. After induction of remission with methylprednisolone pulse therapy, indomethacin, and methotrexate, severe hepatic failure occurred. This patient lacked the typical symptoms of adult onset Still's disease. The second patient was a 32-year-old woman with typical adult onset Still's disease. Remission was induced by high-dose prednisolone and methylprednisolone pulse therapy plus cyclosporine. After she stopped cyclosporine, severe liver dysfunction occurred. In both patients, liver dysfunction occurred during high-dose steroid therapy, and oral cyclosporine (3 mg/kg per day) dramatically improved their liver function. When steroid-resistant severe hepatic failure occurs in patients with adult onset Still's disease, cyclosporine may be the immunosuppressant of choice.
18575164 Relevance of 99mTc-HYNIC-tir-octreotide scintigraphy in a patient affected by sarcoidosis 2008 Mar We report the case of a 59 years old woman affected by lung and joint sarcoidosis, secondary Sjogren's syndrome refractory to common disease-modifying antirheumatic drugs (DMARDs) that regressed with infliximab and methotrexate. 99mTc-HYNIC-TOC scintigraphy was useful in diagnosis, choice of treatment and follow-up.
17371654 Outcome analysis of agility total ankle replacement with prior adjunctive procedures: two 2007 Mar BACKGROUND: A retrospective case review of 65 agility total ankle replacements (64 patients) was done between April, 1998, and March, 2002. The purpose of this study was to more closely identify factors that may be predictive of a favorable outcome, including a comparison of outcome measures between patients who had preoperative corrective procedures and those patients who did not. METHODS: The outcomes of this series of patients were examined with post-operative Short Form (SF)-36 scores as well as chart and radiographic review. Endpoints for this study were amputation, arthrodesis, osteochondral allograft, total ankle revision, or revision of either or both components. The Kaplan-Meier survivorship curve also was estimated including the 95% confidence intervals. RESULTS: Patients with rheumatoid arthritis (RA) were found to have a statistically significant lower rate of failure. Use of a size 1 prosthesis was associated with subsidence and the highest rate of subsequent failure, but fell short of statistical significance (because of the limited power of the study). Smoking, diabetes, and methotrexate use were not associated with an adverse outcome either clinically or statistically, but the number of patients in each group was small. The age of the patient was not a factor in predicting failure of the prosthesis in the posttraumatic arthritis group; however it trended toward significance in the osteoarthritis group. The mean time to failure in patients with osteoarthritis was shorter than in the patients with post-traumatic arthritis but fell just short of statistical significance. CONCLUSIONS: From this series we concluded that rheumatoid arthritis and use of a prosthesis larger than size 1 are predictive factors for better outcome.
17328076 Musculoskeletal abnormalities of the tibia in juvenile rheumatoid arthritis. 2007 Mar OBJECTIVE: To characterize local bone geometry, density, and strength, using peripheral quantitative computed tomography (pQCT), compared with general bone characteristics as measured using dual x-ray absorptiometry (DXA), and to assess their relationship to disease-related factors in children with juvenile rheumatoid arthritis (JRA). METHODS: Forty-eight children ages 4-18 years with JRA (17 pauciarticular, 23 polyarticular, 8 systemic) were compared with age-matched healthy controls (n = 266). Measurements included cortical and trabecular bone geometry, density, and strength at the distal and midshaft tibia determined by pQCT, and whole-body, lumbar spine, and femoral neck measurements by DXA. RESULTS: Methotrexate (MTX) was prescribed to 23 of 48 patients (47.9%) and glucocorticoids and MTX were prescribed to 15 of 48 patients (31.3%), with the greatest use in children with systemic JRA. All JRA patients had decreased tibia trabecular bone density, cortical bone size and strength, and muscle mass. Children with systemic JRA had lower femoral neck densities. Systemic JRA was associated with a shorter, less mineralized skeleton, while a narrower, less mineralized skeleton was observed in polyarticular JRA. The tibia diaphysis was narrower with decreased muscle mass, but normal, size-adjusted bone mineral in all subtypes indicated a localized effect of JRA on bone. Patients exposed to glucocorticoids and MTX or to glucocorticoids or MTX alone had greatly reduced trabecular density, cortical bone geometry properties, and bone mineral content, muscle mass, and bone strength. CONCLUSION: Children with JRA have decreased skeletal size, muscle mass, trabecular bone density, cortical bone geometry, and strength. Not surprisingly, these bone abnormalities are more pronounced in children with greater disease severity.
16763455 Synovial biomarkers in the spondylarthropathies. 2006 Jul PURPOSE OF THE REVIEW: To explore the concept of a biomarker, or surrogate endpoint, to enhance early diagnosis or predict the response to therapeutic intervention in patients with spondylarthropathy. RECENT FINDINGS: Immunopathologic studies have suggested that the features of spondylarthropathy are distinctive, supporting a prominent role for innate immune cells, and can be consistently differentiated from rheumatoid arthritis. Successful treatment of spondylarthropathy synovitis resulted in rapid and sustained decrease in infiltration by macrophage populations and neutrophils, and decreased expression of many proinflammatory mediators. Consistent with studies in rheumatoid arthritis, significant correlations between the effects of both methotrexate and infliximab on disease activity and sublining macrophage populations were reported. These observations highlight the possibility that macrophage populations may be a synovial tissue biomarker of therapeutic intervention in spondylarthropathy. Preliminary studies have evaluated advanced genomic and proteomic methodologies in spondylarthropathy. SUMMARY: Defining the immunopathology of spondylarthropathy has been associated with identifying potential biomarkers of the clinical response to therapeutic intervention. A surrogate marker of arthritis activity in spondylarthropathy could profoundly enhance screening for efficacy and optimization of dose ranges in early-phase randomized clinical trials.
17701269 Adult onset Still's disease: a study of 14 cases. 2008 Jan We studied the clinical profile, laboratory parameters, disease course, and outcomes of patients with adult onset Still's disease (AOSD). A retrospective analysis of adult patients with Still's disease diagnosed from 2000 to 2004 was carried out. Their clinical features and laboratory findings at presentation, disease course, and outcomes were analyzed. Data of 14 patients with Still's disease were analyzed. The age at disease onset ranged from 16 to 59 years with a mean of 29.85, the male to female ratio being 9:5. The mean duration of illness from onset of symptoms to presentation was 14.5 months (range). The most common clinical manifestations were fever (n = 14), articular symptoms (n = 14), rash (n = 8), weight loss (n = 12), and sore throat (n = 5). Elevated ESR was present in all patients with a mean of 98.3 mm at 1 h. Hepatic enzymes were elevated in seven patients at disease onset. The mean duration of follow up was 19.14 months (range). Three patients progressed to chronic arthropathy. Cyclosporine led to dramatic recovery in five patients. Macrophage activation syndrome (MAS) was present in two patients, one after sulfasalazine therapy. One patient with MAS died. Still's disease, although uncommon, has characteristic constellation of clinical and laboratory features and should be considered in the differential diagnosis of fever of unknown origin. Nonsteroidal anti-inflammatory drugs, steroids, and methotrexate may not be always effective, and cyclosporine is an effective drug in resistant cases. Sulfasalazine should be avoided in cases of AOSD.
17997783 Bilateral periocular psoriasis: an initial manifestation of acute generalized pustular pso 2007 Nov A 21-year-old febrile lady presented to the emergency service with severe lid oedema, conjunctivitis, dry mouth and abdominal skin rash. Over 5 days, she developed silvery scales and pustules on the lids, and generalized pustules on an erythematous base. Multiple focal sterile corneal infiltrates were seen. Haematological investigations and a skin biopsy were done as the consulting dermatologist suspected acute generalized pustular psoriasis. In addition, secondary Sjögren's syndrome was diagnosed since she had keratoconjunctivitis sicca, xerostomia, raised erythrocyte sedimentation rate and positive antinuclear antibodies. The presence of microabscesses in the epidermis on skin biopsy confirmed the diagnosis of pustular psoriasis. With oral methotrexate 7.5 mg weekly and topical corticosteroids, the acute condition gradually resolved; however, the keratoconjunctivitis sicca is persisting. Secondary Sjögren's syndrome associated with acute generalized pustular psoriasis and ocular psoriasis is extremely rare. Awareness of the ocular and dermatological features of these two conditions would result in earlier diagnosis and institution of appropriate treatment.
21794420 [Treatment of rheumatoid arthritis with anakinra: a systematic review]. 2007 Jul OBJECTIVE: To perform a systematic review for evaluating efficacy and safety of anakinra in the treatment of rheumatoid arthritis (RA). MATERIAL AND METHOD: The MedLine, Embase, and Cochrane Library databases were searched from January 2000 to February 2006 by using a high sensitive search that included every randomised controlled trial (RCTs) or controlled trial (CTs) that evaluated either efficacy or safety of Anakinra for the treatment of RA. RESULTS: The search identified four relevant studies to evaluate efficacy. Patients treated with anakinra achieved significantly better clinical responses than those treated with placebo. Anakinra combined with methotrexate provided significantly greater clinical benefit than methotrexate alone. Combination therapy with etanercept and anakinra provides no added benefit and an increased safety risk compared with etanercept alone. Results from a large, placebo-controlled safety study demonstrate that anakinra is safe and well tolerated. The most common adverse effect was a mild local inflammation over the puncture area. CONCLUSIONS: This review confirmed both the efficacy and the safety of anakinra in the short term for the treatment of RA. Anakinra provides adequate clinical responses without major safety problems. This systematic review does not allow us to conclude on Anakinra responses in the long term.
17274865 [Macrophage activation syndrome in Chinese children with systemic onset juvenile idiopathi 2006 Nov OBJECTIVE: To review and analyze the clinical features, treatment, and outcome of macrophage activation syndrome (MAS) in children with systemic onset juvennil rheumatoid arthritis (SOJRA). METHOD: Retrospective review and analysis were performed on cases with MAS from a prospectively collected database of children with SOJRA from the year of 2003 to 2006 in the Hospital. RESULTS: Twenty four patients (21 boys, 3 girls) were diagnosed as having MAS with SOJRA. Mean age of the patients with MAS at diagnosis was 7 years, and the duration prior to diagnosis of MAS was 12 months. No trigger factors were found except in one case whose MAS was triggered by use of methotrexate and in another by parvovirus B19 infection. High grade fever, new onset hepatosplenomegaly and lymphadenopathy, pancytopenia, liver dysfunction were common clinical features in all the 24 cases (100%). Bleeding from skin, mucous membrane and gastrointestinal tract were noted in 9 cases (38%). Twelve (50%) cases had CNS dysfunction (high intracranial pressure, seizure and coma). Six cases (25%) developed ARDS. One patient suffered from renal damage. The laboratory test revealed elevated live enzymes and ferritin, decreased value of ESR, albumin, complete blood count and fibrinogen in all the 24 cases. Bone marrow examination supported the diagnosis of definite hemophagocytosis in the 24 cases. Lymph node biopsy was done for one case and histopathological examination showed that the node was full of activated macrophage. As to treatment, five cases only received high dose steroids (three of them died), 14 cases were treated with high dose steroids plus cyclosporine (one died), two were treated with steroids plus cyclosporine and etoposide (none died). The causes of deaths were ARDS and CNS involvement. In three of the cases who died, treatment was given up by their parents. CONCLUSIONS: MAS is a rare and potentially fatal complication of SOJRA. Most of our patients were male. Bone marrow studies support the diagnosis. CNS involvement and ARDS were poor prognostic signs. Early diagnosis and aggressive therapy are essential.
17645785 Celastrus aculeatus Merr. suppresses the induction and progression of autoimmune arthritis 2007 Complementary and alternative medicine products are increasingly being used for the treatment of autoimmune diseases. However, the mechanisms of action of these agents are not fully defined. Using the rat adjuvant arthritis (AA) model of human rheumatoid arthritis, we determined whether the ethanol extract of Celastrus aculeatus Merr. (Celastrus), a Chinese herb, can down-modulate the severity of AA, and also examined the Celastrus-induced changes in immune responses to the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65). AA was induced in the Lewis (LEW; RT.1l) rat by immunization subcutaneously with heat-killed M. tuberculosis H37Ra (Mtb). Celastrus was fed to LEW rats by gavage daily, beginning either before Mtb challenge (preventive regimen) or after the onset of AA (therapeutic regimen). An additional group of rats was given methotrexate for comparison. All rats were graded regularly for the signs of arthritis. In parallel, the draining lymph node cells of Celastrus-treated rats were tested for proliferative and cytokine responses, whereas their sera were tested for the inflammatory mediator nitric oxide. Celastrus feeding suppressed both the induction as well as the progression of AA, and the latter effect was comparable to that of methotrexate. Celastrus treatment induced relative deviation of the cytokine response to anti-inflammatory type and enhanced the production of anti-Bhsp65 antibodies, which are known to be protective against AA. Celastrus feeding also reduced the levels of nitric oxide. On the basis of our results, we suggest further systematic exploration of Celastrus as an adjunct therapeutic modality for rheumatoid arthritis.
17056293 Rheumatologic manifestations of chronic hepatitis C infection. 2006 Dec The many rheumatologic manifestations associated with chronic hepatitis C virus (HCV) infection include arthralgia, myalgia, arthritis, vasculitis, and sicca syndrome. Arthralgia is the most common extrahepatic manifestation and may indicate mixed cryoglobulinemia or an adverse reaction to interferon therapy. HCV arthritis unrelated to cryoglobulinemia is far less common but constitutes an independent entity. The picture may mimic rheumatoid arthritis (RA), particularly as rheumatoid factor is present in 50-80% of cases. Tests are usually negative for antibodies to cyclic citrullinated peptides (anti-CCP), which may help to differentiate the two conditions. The management of HCV arthritis is empirical and poorly standardized. Although low-dose glucocorticoid therapy, hydroxychloroquine, and methotrexate have been used successfully in several patients, little is known about their hepatic safety profile. Arthritis associated with cryoglobulinemia usually responds to antiviral treatment. Sicca syndrome is common in patients with chronic HCV infection and shares similarities with primary Sjögren syndrome, suggesting that HCV infection may deserve to be included among the causes of secondary Sjögren syndrome. HCV-associated vasculitis is usually related to cryoglobulinemia, although a few cases of polyarteritis nodosa-like disease affecting the medium-sized vessels have been reported. Other conditions reported in patients with chronic HCV infection include fibromyalgia, systemic lupus erythematosus (SLE), antiphospholipid syndrome, and osteosclerosis.
21794410 [Diagnostic accuracy of physical examination of the knee in rheumatoid arthritis: clinical 2007 May INTRODUCTION: In patients with rheumatoid arthritis (RA), knee pain can be inflammatory, mechanical or extraarticular. The physical examination (PE) doesn't always detect the presence of knee joint effusion or Baker's cyst (BC) in the knees of these patients. OBJECTIVE: To determine the diagnostic accuracy of PE in the diagnosis of effusion and BC in patients with RA evaluated with musculoskeletal ultrasound (MSUS), using this technique as the gold standard for comparison. MATERIAL AND METHOD: Three different models of ultrasound machines with a 7.5 MHz linear probe were used (Toshiba Tosbee, Toshiba Capasee and Siemens Sonoline). A rheumatologist evaluated the presence or absence of knee joint effusion or BC in patients. We registered age, gender, time of evolution of RA, rheumatoid factor, treatment, functional class of RA (FCRA) and previous clinical diagnosis to the MSUS study. RESULTS: 40 patients (80 knees) with RA were evaluated. Eighty percent were women, mean age 61.3±15 years. Time since onset of RA was 9.5±11.3 years, rheumatoid factor was positive in 80%, FCRA I (3 patients), FCRA II (27), FCRA III (8), FCRA IV (2). Fifty five percent of the patients received methotrexate. Patients reffered pain in 26 knees (32.5%). Joint effusion was reported by the clinician in 35 knees (43.7%) and corroborated by MSUS in 31 knees (38.75%), BC was reported by the clinician in 12 knees (15%) and corroborated by MSUS in 6 knees (7.5%). The sensitivity of the PE for detection of joint effusion was 0.63 and specificity of 0.87, for the detection of BC was 0.43 and 0.91, respectively. CONCLUSIONS: The PE showed acceptable diagnostic accuracy for the clinician. The complementary use of the MSUS can change the therapeutic and diagnostic approach in patients with RA.
17706449 Efficacy of thalidomide in systemic onset juvenile rheumatoid arthritis. 2007 Oct Thalidomide is an immunomodulating agent which reverses many of the cytokine disturbances seen in systemic onset juvenile idiopathic arthritis (SoJIA) with inadequate response to other treatments. We report 3 cases of recalcitrant SoJIA which improved dramatically after treatment with thalidomide. PATIENTS: Three children aged 9, 8, and 6 years diagnosed with SoJIA treated with conventional therapy including NSAIDs, corticosteroids, methotrexate and etanercept failed to respond fully and their condition worsened. Thalidomide was begun based on two previous reports showing its efficacy in recalcitrant SoJIA. RESULTS: Thalidomide produced successful remission of the disease in all 3 patients according to the preliminary criteria for inactive disease and clinical remission of JIA. CONCLUSION: Thalidomide may be a viable, alternative corticoid-sparing therapy in patients with recalcitrant, multidrug-resistant SoJIA.
18408252 Targeted drug delivery by in vivo coupling to endogenous albumin: an albumin-binding prodr 2008 Aug OBJECTIVE: To examine the effect of an albumin-binding prodrug of methotrexate (MTX) in the treatment of murine collagen-induced arthritis (CIA). METHODS: The prodrug AWO54 with the formula EMC-d-Ala-Phe-Lys-Lys-MTX binds selectively to the cysteine-34 position of endogenous albumin, which acts as a macromolecular drug carrier for MTX to the site of inflammation. The CIA model was used to evaluate the anti-arthritic effect of the compound after intravenous application. RESULTS: The albumin-bound form of AWO54 was efficiently cleaved by cathepsin B and plasmin, two proteases that are overexpressed in rheumatoid arthritis, and release a MTX lysine derivative. AWO54 suppressed CIA in a dose-dependent manner and was significantly better than MTX. To obtain a similar effect only about 20% of the MTX-equivalent dose of AWO54 had to be given. The efficacy of the drug was tested in two different stages of CIA: while both, MTX and AWO54 inhibited arthritis in an early stage of the disease, in a later stage only AWO54 showed a significant inhibitory effect in comparison with control. CONCLUSION: Targeted drug delivery by in vivo coupling of a prodrug of MTX to endogenous albumin is better than MTX in the treatment of CIA.