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P Jobanputra

Publications and source records attributed to P Jobanputra.

At least 19 recordsLinked to original sources
PubMed2006

Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate in acute sensorineural hearing loss.

Patients with autoimmune inner-ear disease (AIED) are treated with high doses of steroids in the short term when suffering an acute hearing loss. As a consequence, substances such as methotrexate have been employed in the role of steroid-sparing agents. Additionally, it is known that tumour necrosis factor alpha (TNFalpha) is an important mediator of the inflammatory process, inhibition of which may be of benefit in AIED. This case report illustrates the use of a TNFalpha inhibitor in combination with methotrexate, which is known to be an effective combination in rheumatoid arthritis but has yet to be described for sensorineural hearing loss. We conclude that progressive AIED may respond well to TNFalpha inhibition, whilst more difficult cases, such as this example, could benefit from combining such therapy with methotrexate.

Autoimmune Diseases↗
PubMed2006

A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness.

OBJECTIVES: This report reviews the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab, agents that inhibit tumour necrosis factor-alpha (TNF-alpha), when used in the treatment of rheumatoid arthritis (RA) in adults. DATA SOURCES: Electronic databases were searched up to February 2005. REVIEW METHODS: Systematic reviews of the literature on effectiveness and cost-effectiveness were undertaken and industry submissions to the National Institute for Health and Clinical Excellence (NICE) were reviewed. Meta-analyses of effectiveness data were also undertaken for each agent. The Birmingham Rheumatoid Arthritis Model (BRAM), a simulation model, was further developed and used to produce an incremental cost-effectiveness analysis. RESULTS: Twenty-nine randomised controlled trials (RCTs), most of high quality, were included. The only head-to-head comparisons were against methotrexate. For patients with short disease duration (<or=3 years) who were naïve to methotrexate, adalimumab was marginally less and etanercept was marginally more effective than methotrexate in reducing symptoms of RA. Etanercept was better tolerated than methotrexate. Both adalimumab and etanercept were more effective than methotrexate in slowing radiographic joint damage. Etanercept was also marginally more effective and better tolerated than methotrexate in patients with longer disease durations who had not failed methotrexate treatment. Infliximab is only licensed for use with methotrexate. All three agents, either alone (where so licensed) or in combination with ongoing disease-modifying antirheumatic drugs (DMARDs), were effective in reducing the symptoms and signs of RA in patients with established disease. At the licensed dose, the numbers needed to treat (NNTs) (95% CI) required to produce an American College for Rheumatology (ACR) response compared with placebo were: ACR20: adalimumab 3.6 (3.1 to 4.2), etanercept 2.1 (1.9 to 2.4), infliximab 3.2 (2.7 to 4.0); ACR50: adalimumab 4.2 (3.7 to 5.0), etanercept 3.1 (2.7 to 3.6), infliximab 5.0 (3.8 to 6.7); and ACR70: adalimumab 7.7 (5.9 to 11.1), etanercept 7.7 (6.3 to 10.0), infliximab 11.1 (7.7 to 20.0). In patients who were naïve to methotrexate, or who had not previously failed methotrexate treatment, a TNF inhibitor combined with methotrexate was significantly more effective than methotrexate alone. Infliximab combined with methotrexate had an increased risk of serious infections. All ten published economic evaluations met standard criteria for quality, but the incremental cost-effectiveness ratios (ICERs) ranged from being within established thresholds to being very high because of varying assumptions and parameters. All three sponsors who submitted economic models made assumptions favourable to their product. BRAM incorporates improvements in quality of life and mortality, but assumes no effect of TNF inhibitors on joint replacement. For use in accordance with current NICE guidance as the third DMARD in a sequence of DMARDs, the base-case ICER was around pound30,000 per quality-adjusted life-year (QALY) in early RA and pound50,000 per QALY in late RA. Sensitivity analyses showed that the results were sensitive to the estimates of Health Assessment Questionnaire (HAQ) progression while on TNF inhibitors and the effectiveness of DMARDs, but not to changes in mortality ratios per unit HAQ. TNF inhibitors are most cost-effective when used last. The ICER for etanercept used last is pound24,000 per QALY, substantially lower than for adalimumab ( pound30,000 per QALY) or infliximab ( pound38,000 per QALY). First line use as monotherapy generates ICERs around pound50,000 per QALY for adalimumab and etanercept. Using the combination of methotrexate and a TNF inhibitor as first line treatment generates much higher ICERs, as it precludes subsequent use of methotrexate, which is cheap. The ICERs for sequential use are of the same order as using the TNF inhibitor alone. CONCLUSIONS: Adalimumab, etanercept and infliximab are effective treatments compared with placebo for RA patients who are not well controlled by conventional DMARDs, improving control of symptoms, improving physical function, and slowing radiographic changes in joints. The combination of a TNF inhibitor with methotrexate was more effective than methotrexate alone in early RA, although the clinical relevance of this additional benefit is yet to be established, particularly in view of the well-established effectiveness of MTX alone. An increased risk of serious infection cannot be ruled out for the combination of methotrexate with adalimumab or infliximab. The results of the economic evaluation based on BRAM are consistent with the observations from the review of clinical effectiveness, including the ranking of treatments. TNF inhibitors are most cost-effective when used as last active therapy. In this analysis, other things being equal, etanercept may be the TNF inhibitor of choice, although this may also depend on patient preference as to route of administration. The next most cost-effective use of TNF inhibitors is third line, as recommended in the 2002 NICE guidance. Direct comparative RCTs of TNF inhibitors against each other and against other DMARDs, and sequential use in patients who have failed a previous TNF inhibitor, are needed. Longer term studies of the quality of life in patients with RA and the impact of DMARDs on this are needed, as are longer studies that directly assess effects on joint replacement, other morbidity and mortality.

Adalimumab↗
PubMed2005

Quality of care for NSAID users: development of an assessment tool.

OBJECTIVE: Assessments of NSAID use based on authoritative guidelines typically overlook patients' views and nuances of medical history. Our objective was to develop an assessment tool that incorporates these aspects, and technical items, for quality of care assessments in NSAID users. METHODS: Patients newly referred to a university hospital were interviewed by a nurse using an agreed template. A multidisciplinary group of rheumatologists, nurse specialists, primary care physicians and a pharmacist reviewed current guidance and systematic reviews on NSAID use, and a series of interview transcripts. The group agreed, by informal consensus, important determinants of effective and safe NSAID use. Technical aspects of medical care and items that reflected interpersonal care were included in an index for assessing quality of care for individual patients. Interview transcripts of 100 patients were scored by panel members and reliability of scores was tested by calculating weighted percentage agreement and the kappa statistic. RESULTS: Our final index had five domains: medical risk factors; steps taken to reduce risk; knowledge of adverse effects; NSAID dose; and cost efficiency. Each item was scored 0, 1 or 2. Scores were summed, giving a maximum of 10 (low scores indicating low quality). Intra-rater agreement was >90%; kappa was 0.47-0.87 for individual domains and 0.59 for overall score. Inter-rater agreement for overall score was 95%; kappa was 0.25-0.78 for domains and 0.48 for overall score. Patients with especially low scores were identified using the mode of scores for five assessors; obvious clinical concerns were identified, supporting index face validity. CONCLUSIONS: A simple index to evaluate quality of care for NSAID users based on a patient interview is described. This may be used by one or more assessors to examine care standards and highlight deficiencies in relation to NSAID use in practice.

Adolescent↗
PubMed2005

Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation.

OBJECTIVE: To support a review of the guidance issued by the National Institute for Health and Clinical Excellence (NICE) in December 2000 by examining the current clinical and cost-effectiveness evidence on autologous cartilage transplantation. DATA SOURCES: Electronic databases. REVIEW METHODS: Evidence on clinical effectiveness was obtained from randomised trials, supplemented by data from selected observational studies for longer term results, and for the natural history of chondral lesions. Because of a lack of long-term results on outcomes such as later osteoarthritis and knee replacement, only illustrative modelling was done, using a range of assumptions that seemed reasonable, but were not evidence based. RESULTS: Four randomised controlled trials were included, as well as observational data from case series. The trials studied a total of 266 patients and the observational studies up to 101 patients. Two studies compared autologous chondrocyte implantation (ACI) with mosaicplasty, the third compared ACI with microfracture, and the fourth compared matrix-guided ACI (MACI) with microfracture. Follow-up was 1 year in one study, and up to 3 years in the remaining three studies. The first trial of ACI versus mosaicplasty found that ACI gave better results than mosaicplasty at 1 year. Overall, 88% had excellent or good results with ACI versus 69% with mosaicplasty. About half of the biopsies after ACI showed hyaline cartilage. The second trial of ACI versus mosaicplasty found little difference in clinical outcomes at 2 years. Disappointingly, biopsies from the ACI group showed fibrocartilage rather than hyaline cartilage. The trial of ACI versus microfracture also found only small differences in outcomes at 2 years. Finally, the trial of MACI versus microfracture contained insufficient long-term results at present, but the study does show the feasibility of doing ACI by the MACI technique. It also suggested that after ACI, it takes 2 years for full-thickness cartilage to be produced. Reliable costs per quality-adjusted life-year (QALY) could not be calculated owing to the absence of necessary data. Simple short-term modelling suggests that the quality of life gain from ACI versus microfracture would have to be between 70 and 100% greater over 2 years for it to be more cost-effective within the 20,000--30,000 pounds sterling per QALY cost-effectiveness thresholds. However, if the quality of life gains could be maintained for a decade, increments relative to microfracture would only have to be 10--20% greater to justify additional treatment costs within the cost-effectiveness band indicated above. Follow-up from the trials so far has only been up to 2 years, with longer term outcomes being uncertain. CONCLUSIONS: There is insufficient evidence at present to say that ACI is cost-effective compared with microfracture or mosaicplasty. Longer term outcomes are required. Economic modelling using some assumptions about long-term outcomes that seem reasonable suggests that ACI would be cost-effective because it is more likely to produce hyaline cartilage, which is more likely to be durable and to prevent osteoarthritis in the longer term (e.g. 20 years). Further research is needed into earlier methods of predicting long-term results. Basic science research is also needed into factors that influence stem cells to become chondrocytes and to produce high-quality cartilage, as it may be possible to have more patients developing hyaline cartilage after microfracture. Study is also needed into cost-effective methods of rehabilitation and the effect of early mobilisation on cartilage growth.

Cartilage, Articular↗
PubMed2004

The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis.

OBJECTIVES: To address the structural issues relating to mortality and quality of life (QoL) effects and to identify data on the general pattern of QoL of rheumatoid arthritis (RA) patients through a restructured and enhanced version of the Birmingham Preliminary Model (BPM). DATA SOURCES: Electronic databases and a postal survey of current UK rheumatological practice. REVIEW METHODS: The focus for this report was to evaluate two new drugs, etanercept and infliximab [antibodies against tumour necrosis factor (anti-TNFs)], for use in the treatment of RA using the Birmingham Rheumatoid Arthritis Model (BRAM). Having carried out a rapid systematic review of physician surveys of current disease-modifying antirheumatic drugs (DMARDs) usage patterns in adult patients with RA and a postal survey of consultant rheumatologists working in the UK, the drug sequences were then identified for the model. A series of analyses were then run using the model. The issue of specifying the correct comparison in the analysis being undertaken was investigated using two separate analyses: the situation of comparing anti-TNFs with placebo, and the comparison of a sequence using anti-TNFs with a sequence that represents current practice in the UK. RESULTS: Results from the survey of rheumatologists highlighted the fact that RA has different manifestations and responds to different agents in different patients, all of which makes any summary of practice difficult to achieve and open to the criticism of being an oversimplification. However, the findings generally agree with other surveys and trends observed, such as the increasing acceptance of methotrexate as first line drug of choice in patients with RA, especially if the disease is of an aggressive nature. The newer anti-TNF agents have also begun to be incorporated into use. The incremental cost-effectiveness ratios resulting from the use of an inappropriate comparator of placebo were consistently lower than in the base case where appropriate comparator drugs sequences are used. The focus of the BRAM on a drug sequence helped to avoid the incremental cost-effectiveness of new treatments appearing lower than they really are when inappropriate comparators are used. To test the effect on the analysis results of using the disease-modifying antirheumatic sequence that represents current UK practice, the BRAM was run for the strategies representing current UK practice. The results were not very different from the base-case results. CONCLUSIONS: The main achievement of this work was to bring about a more realistic modelling of real-life clinical pathways and events, as it has developed from the BPM to the BRAM. This has been brought about by overcoming structural and data limitations. In addition, the modelling approach reflected in the BRAM is applicable to other chronic conditions, especially those where a sequential approach to therapeutic options exists. The model has been successfully restructured so that different sequences of treatment can readily be considered, including the sequence that best represents current clinical practice in the UK. In addition, the flexibility inherent in using a modelling approach to consider these health policy questions has been demonstrated. One of the key uncertainties that can now be explored concerns the impact of new drugs on disease progression. Current evidence on this is weak, but should new agents demonstrate such a benefit then the BRAM may be a suitable vehicle through which to investigate the costs and full effects. Inevitably, there remain problems and limitations with the BRAM, but these are almost entirely data limitations. As data on these issues become available the BRAM provides a convenient tool through which reanalysis might be undertaken.

Adolescent↗
PubMed2004

The clinical and cost-effectiveness of anakinra for the treatment of rheumatoid arthritis in adults: a systematic review and economic analysis.

OBJECTIVES: To review the evidence of the clinical and cost-effectiveness of anakinra, an interleukin-1 receptor antagonist (IL-1Ra), for the treatment of rheumatoid arthritis (RA) in adults. DATA SOURCES: Electronic bibliographic databases. Scrip, Food and Drug Administration (FDA) submissions for new drug applications, European Agency for the Evaluation of Medicinal Products (EMEA) reports and the pharmaceutical company submission to the National Institute for Clinical Excellence. REVIEW METHODS: Studies were identified that included randomised controlled trials (RCTs) or economic evaluations of anakinra in adult patients with RA. Existing health economic reviews were also assessed. Data were extracted and quality assessed using a structured approach. The Birmingham Rheumatoid Arthritis Model (BRAM) was used to compare disease-modifying antirheumatic drug (DMARD) sequences, chosen to reflect current clinical practice, with and without anakinra, at different points in the DMARD sequence. RESULTS: Five high-quality RCTs of anakinra in adult patients with RA, involving a total of 2905 patients, of whom 2146 received anakinra, were identified. The results of the clinical trials were consistent with clinical benefit (compared with placebo) as measured by American College of Rheumatology (ACR) composite response rate at 6 months. Variation in response rate was seen across the trials, which is likely to be a reflection of the size of the trials and the wide range of doses evaluated. Consistent benefit was seen at the higher dose evaluated. Benefit was evident both with monotherapy and when used in combination with methotrexate. Data on the efficacy end-points evaluated in a large pragmatic safety study have not been made available, which is of concern. Anakinra treatment was associated with a high incidence of injection-site reactions. Serious adverse events were infrequent, but longer term follow-up is required. No fully published economic evaluations of anakinra in patients with RA were identified. The BRAM gives a base-case estimate of the incremental cost-effectiveness ratio (ICER) of anakinra of 106,000 pounds to 604,000 pounds/quality-adjusted life-year (QALY). In the sensitivity analyses substantial variations were made in key parameters and ICERs were shown to be responsive. However, ICERs did not drop below 50,000 pounds/QALY in any univariate sensitivity analysis. CONCLUSIONS: Anakinra can be considered modestly effective in the treatment of RA based on ACR response, although no conclusion can currently be made on the effect of treatment on disease progression. Adjusted indirect comparison suggests that anakinra may be significantly less effective at relieving the clinical signs and symptoms of RA, as measured by the ACR response criteria, than tumour necrosis factor (TNF) inhibitors all used in combination with methotrexate, although these results should be interpreted with caution. The BRAM produces an ICER for anakinra substantially higher than those for infliximab and etanercept. However, patients may respond to anakinra when they have not responded to other TNF inhibitors, as these agents have a different mechanism of action. Thus, anakinra may produce a clinically significant and important improvement in some patients that they could not otherwise have achieved. Further research would be valuable in the following areas: RCTs to evaluate the efficacy, safety and cost of anakinra over the longer term; comparative trials of anakinra with other DMARDs and biological modifiers; assessment of the role of anakinra in the treatment of patients who have failed to achieve a benefit while taking infliximab or etanercept; assessment on the impact of DMARDs and anakinra on joint replacement, mortality and quality of life; controlled clinical trials of combination therapy with two anticytokines; investigations into newer biological therapies; and the utility of radiographic outcomes in clinical trials of RA.

Adult↗
PubMed2003

A survey of British rheumatologists' DMARD preferences for rheumatoid arthritis.

OBJECTIVE: To determine the current disease-modifying anti-rheumatic drug (DMARD) preferences of UK consultant rheumatologists. METHODS: A questionnaire was sent in May 2002. We asked which DMARD(s) was most frequently preferred first and sought the most typical sequence of DMARDs, including DMARD combinations. Also we determined the extent to which prognostic and other factors influenced treatment choices. Comments were invited, written responses abstracted and key themes identified. RESULTS: After two mailings, 331 (of 460; 72%) suitable questionnaires were returned. Ninety-five per cent (315/331) preferred methotrexate (154, 46.5%) or sulphasalazine (144, 43.5%) or either of these two (17, 5%) as first-choice agent. Of those who chose methotrexate first, 80% (123/154) ranked sulphasalazine second, 45% (55/123) combined sulphasalazine and methotrexate and 49% (27/55) then added hydroxychloroquine to this combination, in active disease. Of those who chose sulphasalazine first, 95% (137/144) ranked methotrexate second, 75% (113/150) preferring methotrexate monotherapy and 12% (18/150) the combination with sulphasalazine. Rheumatologists who preferred sulphasalazine first more commonly used subsequent DMARDs singly than those who started with methotrexate (P < 0.0001). Leflunomide was more commonly preferred than intramuscular gold as third choice (52/145 vs 29/145; P < 0.003). The most popular sequence of DMARDs was methotrexate or sulphasalazine, singly or in combination, leflunomide, intramuscular gold and anti-tumour necrosis factor therapy. Poor prognostic factors influenced DMARD choice, but patient occupation and drug costs did not. CONCLUSION: Methotrexate has displaced other DMARDs, especially sulphasalazine, as agent of first choice and newer agents have displaced older DMARDs. Whether the expressed preference for particular DMARDs accurately reflects actual use, and is optimal in rheumatoid arthritis, remains to be determined.

Antirheumatic Agents↗
PubMed2001

Adverse drug reactions.

Explore the source record for details and available documents.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

Successful treatment of severe muscle necrosis with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is an effective treatment for a range of conditions believed to have an autoimmune basis, including inflammatory muscle disease. We describe a patient with muscle disease characterized by severe necrosis without clinical or biopsy evidence of inflammation or vasculitis, who responded to treatment with IVIG.

Biopsy↗
PubMed1997

Hyperpolarisation of cultured human chondrocytes following cyclical pressure-induced strain: evidence of a role for alpha 5 beta 1 integrin as a chondrocyte mechanoreceptor.

Mechanical stimuli influence chondrocyte metabolism, inducing changes in intracellular cyclic adenosine monophosphate and proteoglycan production. We have previously demonstrated that primary monolayer cultures of human chondrocytes have an electrophysiological response after intermittent pressure-induced strain characterised by a membrane hyperpolarisation of approximately 40%. The mechanisms responsible for these changes are not fully understood but potentially involve signalling molecules such as integrins that link extracellular matrix with cytoplasmic components. The results reported in this paper demonstrate that the transduction pathways involved in the hyperpolarisation response of human articular chondrocytes in vitro after cyclical pressure-induced strain involve alpha 5 beta 1 integrin. We have demonstrated, using pharmacological inhibitors of a variety of intracellular signalling pathways, that the actin cytoskeleton, the phospholipase C calmodulin pathway, and both tyrosine protein kinase and protein kinase C activities are important in the transduction of the electrophysiological response. These results suggest that alpha 5 beta 1 is an important chondrocyte mechanoreceptor and a potential regulator of chondrocyte function.

Actins↗
PubMed1997

CD44 expression by leucocytes in rheumatoid arthritis and modulation by specific antibody: implications for lymphocyte adhesion to endothelial cells and synoviocytes in vitro.

Anti-CD44 MoAb IM7 induced the loss of CD44 from mouse leucocytes thereby inhibiting leucocyte migration and joint inflammation in murine arthritis. Thus, targeting CD44 with MoAb may have potential for the treatment of patients with inflammatory joint diseases. Expression of CD44 by peripheral blood (PB) and synovial fluid (SF) leucocytes from rheumatoid arthritis (RA) patients was compared and the ability of IM7 to modulate this expression determined. RASF lymphocytes showed increased CD44 expression compared with those in PB indicative of an activated phenotype. As inflammatory SF did not up-regulate CD44 expression on PB lymphocytes, the increased CD44 expression by SF lymphocytes was a result of the selective homing of CD44(high) cells to the synovium rather than an effect of the synovial environment. RASF granulocytes showed reduced CD44 expression compared with those in PB, again indicative of an activated phenotype. However, this reduction could be induced on PB granulocytes following culture with inflammatory SF and was inhibited by anti-TNF-alpha MoAb, implying that soluble factors in inflammatory SF such as TNF-alpha induced granulocyte activation and CD44 loss. IM7 induced the loss of CD44 from lymphocytes (both from PB and SF) and granulocytes in vitro, but was subsequently re-expressed after 24 h culture in the absence of the MoAb. This loss of CD44 was blocked by serine- and metalloprotease inhibitors implying that IM7 induced the proteolytic cleavage of CD44 by a mechanism similar to that reported for the loss of CD44 from PMA-activated granulocytes. Furthermore, IM7-treated CD44(low) lymphocytes showed reduced adherence to both an endothelial cell line and RA synovial fibroblasts in vitro. The unique ability of IM7 to reduce CD44 expression by lymphocytes suggests that it could prevent lymphocyte extravasation and synovial infiltration in RA as previously reported in murine arthritis.

Antibodies, Monoclonal↗