Rheumatoid Arthritis: Hashkes PJ

Hashkes PJ, Laxer RM. · Department of Rheumatic Diseases A50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. · Curr Rheumatol Rep. · Pubmed #17092444 No free full text.

Abstract: Many exciting developments in the treatment of juvenile idiopathic arthritis (JIA) have emerged recently, including new tools to assess the results of clinical trials (eg, the definition of remission and a radiologic scoring tool). New controlled studies examined the equivalence of meloxicam to naproxen, the efficacy of leflunomide but the superiority of methotrexate, and the use of infliximab in polyarthritis JIA. Initial studies have shown the potential of anti-interleukin (IL)-1 and anti-IL-6 receptor antibody therapy for systemic JIA. Corticosteroid-sparing medications including the use of "biologic modifiers" for JIA-associated uveitis have been described. Evidence-based guidelines for the main subtypes of JIA have been published. However, good evidence on the treatment of several disease subtypes is still lacking. Studies of new medications and the use of combination therapy, including aggressive induction therapy early in the disease course, are necessary to continue improving the outcome of JIA patients.

Hashkes PJ, Laxer RM. · Section of Pediatric Rheumatology, Department of Rheumatic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · JAMA. · Pubmed #16204667 links to  free full text

Abstract: CONTEXT: The treatment of juvenile idiopathic arthritis (JIA) has changed markedly in the last 15 years. Many children with JIA are not treated by pediatric rheumatologists. OBJECTIVE: To review the best evidence for the treatment of JIA. DATA SOURCES: English-language trials of JIA between 1966 and 2005 were searched using MEDLINE, EMBASE, the Cochrane database, and abstracts from recent rheumatology and pediatric scientific meetings. STUDY SELECTION: Randomized controlled trials and open studies including at least 10 patients for medications without controlled trials. DATA EXTRACTION: For studies after 1997, the American College of Rheumatology Pediatric 30 outcome measure was used to define patients as responders. For older studies, the primary response outcome measure defined by the authors was used. DATA SYNTHESIS: Thirty-four controlled studies were identified. Nonsteroidal anti-inflammatory drugs are effective only for a minority of patients, mainly those with oligoarthritis. Intra-articular corticosteroid injections are very effective for oligoarthritis. Methotrexate is effective for the treatment of extended oligoarthritis and polyarthritis and less effective for systemic arthritis. Sulfasalazine and leflunomide may be alternatives to methotrexate. Antitumor necrosis factor medications are highly effective for polyarticular course JIA not responsive to methotrexate but are less effective in systemic arthritis. There is a lack of evidence for the optimal treatment of systemic and enthesitis-related arthritis. CONCLUSIONS: Despite many advances in the treatment of JIA, there is still a lack of evidence for treatment of several disease subtypes. The treatment plan needs to be individualized based on the JIA subtype.

Hashkes PJ, Friedland O, Uziel Y. · Department of Pediatrics and Pediatric Rheumatology Clinics, Rebecca Sieff Hospital, Safed, Israel. · Isr Med Assoc J. · Pubmed #11802310 links to  free full text

This publication has no abstract.

Hashkes PJ, Azaria R. · No affiliation provided · Harefuah. · Pubmed #10883142 No free full text.

This publication has no abstract.

Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhães C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH, Anonymous00184, Anonymous00185. · IRCCS G Gaslini, PRINTO, Genoa, Italy. · Lancet. · Pubmed #18632147 No free full text.

Abstract: BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. FUNDING: Bristol-Myers Squibb.

Ting TV, Hashkes PJ. · Section of Pediatric Rheumatology, Department of Rheumatic Diseases, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. · Clin Exp Rheumatol. · Pubmed #18173932 No free full text.

Abstract: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). Although associated with many mild adverse effects, the short and long-term safety of MTX in JIA has been excellent. While many JIA children treated with MTX develop liver enzyme abnormalities, no cases of irreversible liver damage or of severe non-infectious hepatitis with Reye-like features have been reported in non-systemic JIA. We report a 2-year-old girl with oligoarthritis whose liver enzyme increased to greater than 45 times the upper limit of normal, and developed hypoglycemia and hyperammonemia after 10 months of MTX and naproxen therapy. An infectious and metabolic work-up for other causes was unremarkable. She recovered completely after folinic acid therapy; MTX and naproxen was not restarted. While very rare in JIA, MTX in synergism with naproxen can induce severe liver toxicity and it is important to screen children for liver enzyme abnormalities.

Oliveira S, Ravelli A, Pistorio A, Castell E, Malattia C, Prieur AM, Saad-Magalhães C, Murray KJ, Bae SC, Joos R, Foeldvari I, Duarte-Salazar C, Wulffraat N, Lahdenne P, Dolezalova P, de Inocencio J, Kanakoudi-Tsakalidou F, Hofer M, Nikishina I, Ozdogan H, Hashkes PJ, Landgraf JM, Martini A, Ruperto N, Anonymous00868. · IRCCS G. Gaslini, Pediatria II, Reumatologia, Pediatric Rheumatology International Trials Organization, Genoa, Italy. · Arthritis Rheum. · Pubmed #17266064 links to  free full text

Abstract: OBJECTIVE: To investigate the proxy-reported health-related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA). METHODS: In this multinational, multicenter, cross-sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate. RESULTS: A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean +/- SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 +/- 10.6 versus 54.6 +/- 4.0, P < 0.0001; psychosocial: 47.6 +/- 8.7 versus 51.9 +/- 7.5, P < 0.0001), with the physical well-being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10-cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively. CONCLUSION: We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.

Hashkes PJ, Shajrawi I. · Pediatric Rheumatology Section, Department of Rheumatic Diseases, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. · Clin Exp Rheumatol. · Pubmed #14611117 No free full text.

Abstract: We report the case of a 7-year-old boy who was initially diagnosed as having polyarticular juvenile idiopathic arthritis. Clinical and laboratory features of overt sarcoidosis became evident early during etanercept therapy when he developed acute panuveitis, papular skin rash and elevated levels of angiotensin-converting enzyme. Non-caseating granulomas were present in the liver. Uveitis resolved upon discontinuation of etanercept and systemic administration of corticosteroids. In rare cases expression of autoimmune disorders or expanded clinical features of these disorders may occur during etanercept treatment.

Hashkes PJ. · Pediatric Rheumatology Service, Sieff Hospital, Safed and Poriya Hospital, Tiberias, Israel. · Clin Exp Rheumatol. · Pubmed #12673904 No free full text.

Abstract: BACKGROUND: Several studies from Western countries have analyzed the profile of pediatric rheumatology practices. Due to differences in demography and health care systems the profile in Israel may differ from those countries. OBJECTIVE: To describe the profile of a pediatric rheumatology practice in Israel. METHODS: All new patients seen during the course of 2000 as part of my pediatric rheumatology practice in Northern Israel were registered at their initial encounter. Recorded were demographic data, referral patterns, diagnoses, and disease-related data. Diagnoses were grouped together by types of condition. RESULTS: 242 new patients were seen. 39% of the patients had a rheumatic condition, 39% had non-inflammatory conditions, 12% had periodic fever syndromes and for 10% no definitive diagnosis was determined. 14% had chronic rheumatic diseases. The time until diagnosis was significantly greater and more physicians were involved in the evaluation of periodic fever syndromes than in other disease groups. Seventeen (7%) patients had juvenile rheumatoid arthritis (JRA). The minimum estimated incidence of JRA was 8.8 per 100,000 children. CONCLUSIONS: Most patients seen did not have classic inflammatory rheumatic diseases, similar to data from other Western countries. Distinctive to Israel and the Middle East, periodic fever syndromes comprise a large proportion of the pediatric rheumatology practice. These syndromes are relatively difficult for community physicians to diagnose.

Hashkes PJ. · Pediatric Rheumatology Service, Sieff and Poriya Hospitals, Technion Medical School, Haifa, Israel. · Scand J Rheumatol. · Pubmed #12195633 No free full text.

Abstract: OBJECTIVE: To examine the beneficial effect of climatic therapy at the Tiberias Hot Springs on patients with inflammatory arthritis. METHODS: Patients from Sweden with inflammatory arthritis underwent climatic therapy for 4 weeks at the Tiberias Hot Springs in Israel. Patients were examined at the beginning and end of the therapy and were evaluated as responders according to internationally validated criteria. RESULTS: One hundred-thirty-six patients were evaluated, 83 with a clinical course of rheumatoid arthritis (RA) and 53 with ankylosing spondylitis (AS). Forty-seven (57%) of the RA patients and 32 (60%) of the AS patients were considered responders. Shorter disease duration and more active disease were associated with a greater response in RA, while in AS males responded more often than females. CONCLUSION: Most patients benefited significantly from climatic therapy. Long-term follow-up is necessary to see whether improvement is sustained and if work ability and hospitalizations are also improved.

Hashkes PJ, Balistreri WF, Bove KE, Ballard ET, Passo MH. · Department of Pediatrics, Rebecca Sieff and Poriah Hospitals, Safed and Tiberias, Israel. · J Pediatr. · Pubmed #9880448 No free full text.

Abstract: OBJECTIVE: To examine the relationship between hepatotoxic risk factors and liver histopathology in patients with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). STUDY DESIGN: We graded the histology of 33 percutaneous liver biopsy specimens from 25 patients with JRA treated at Children's Hospital Medical Center, Cincinnati, Ohio, using the Roenigk Classification Scale. Stepwise linear and logistic regression analyses were performed to examine the relationship of the Roenigk grade and presence of liver fibrosis of biopsy specimens with potential risk factors. RESULTS: Twenty-seven biopsy specimens (82%) were classified as grade I, 4 (12%) as grade II, and 2 (6%) as grade IIIA; none demonstrated significant fibrosis. The frequency of biochemical abnormalities (P <.001) and body mass index (P =.05) were the only risk factors found to significantly relate to the Roenigk grade. The following factors were not significantly associated with the Roenigk grade: age, gender, disease duration, JRA subtype and course, duration of MTX administration, weekly MTX dose, cumulative dose of MTX, route of MTX administration, use of folic acid supplementation, concurrent use of other medications, and potential hepatotoxic comorbidities. CONCLUSIONS: Serial biochemical abnormalities are significantly associated with Roenigk grade and the presence of liver fibrosis. These findings concur with studies of patients with rheumatoid arthritis, suggesting that guidelines for monitoring MTX hepatotoxicity in rheumatoid arthritis may be applicable to patients with JRA.