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Treatment of Polymyalgia Rheumatica and Giant Cell Arteritis: Are We Any Further Forward?

Raashid Luqmani, DM
[+] Article and Author Information

From Botnar Research Centre, University of Oxford, Oxford OX3 7LD, United Kingdom


Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Raashid Luqmani, DM, Rheumatology Department, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, United Kingdom; e-mail, raashid.luqmani@ndos.ox.ac.uk.


Ann Intern Med. 2007;146(9):674-676. doi:10.7326/0003-4819-146-9-200705010-00011
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Giant cell arteritis (GCA) and polymyalgia rheumatica are common overlapping inflammatory rheumatic diseases of unknown cause that share some clinical features and affect patients older than 50 years. The age-adjusted annual incidence of GCA is 188 to 220 cases per 1 million persons (12) in the United States and the United Kingdom and 290 per 1 million persons in Norway (3). The annual incidence of polymyalgia rheumatica varies from 120 per 1 million persons in Italy (4) to 1120 per million in Norway (3) and is higher in women than men.

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A potential role for TNF-blocking agents in polymyalgia rheumatica and giant cell arteritis
Posted on May 17, 2007
Carlo Salvarani
Arcispedale S. Maria Nuova, Reggio Emilia, Italy
Conflict of Interest: None Declared

A potential role for TNF-blocking agents in polymyalgia rheumatica and giant cell arteritis: comment on the editorial by Luqmani

Carlo Salvarani, MD and Gene G. Hunder, MD*

from Servizio di Reumatologia (C.S), Arcispedale S. Maria Nuova, Reggio Emilia, Italy; and *Professor Emeritus, Division of Rheumatology (G.G.H.), Mayo Clinic, Rochester, Minnesota, USA.

Address reprint requests to Carlo Salvarani, Servizio di Reumatologia, Arcispedale S. Maria Nuova, Viale Risorgimento N80, 42100 Reggio Emilia, Italy. E-mail: salvarani.carloåsmn.re.it.

TO THE EDITOR: We agree with the conclusions of the insightful editorial of Dr Luqmani about the two randomized controlled trials (RCT) of infliximab in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), especially that corticosteroids (CS) are still the cornerstome of treatment of these two related diseases (1). However, although these two studies showed that adding infliximab to prednisone is of no benefit in GCA and PMR patients, a corticosteroid-sparing effect for TNF-blockers in these two conditions can not be completely excluded. As Dr Luqmani commented these two trials were designed to detect a large effect of infliximab because of the drugs expense and possible adverse effects. The two studies were too small to definitively identify small benefits. A second point can be raised in favour of a possible therapeutic benefit for TNF-blocking agents. These two RCTs enrolled patients with newly diagnosed PMR and GCA. The two open pilot studies which preceded these RCTs observed the efficacy of infliximab in reducing corticosteroid requirements in patients with longstanding, relapsing PMR and GCA (2, 3). In these patients the potent anti-inflammatory effect of infliximab was demonstrated by the reduction of acute phase reactants, including IL-6 circulating levels, two weeks after the start of therapy. The reduction in IL-6 levels was of particular interest, as the persistence of elevated levels of this cytokine characterized the patients with continued active disease who require higher and more prolonged CS doses (2). It is possible that TNF-blocking agents are effective in subsets of PMR and GCA characterized by a more chronic relapsing course. A third recent open study from our group suggest that also etanercept may be a useful CS- sparing agent in PMR patients with refractory disease, that is, patients with more severe disease (4). The efficacy of TNF-blockers in patients with relapsing disease also has a pathophysiological basis. The elegant study of Hernandez-Rodriguez and colleagues showed that high TNF-alpha production was associated in GCA with longer steroid requirements and relapsing disease (5). Therefore, before completely excluding a potential therapeutic role for TNF-blockers in PMR or GCA, we suggest that RCTs should be performed enrolling only PMR and GCA patients with relapsing or refractory disease.

References

1. Luqmani R. Treatment of polymyalgia rheumatica and giant cell arteritis: are we any further forward? Ann Intern Med 2007; 146:674-6.

2. Salvarani C, Cantini F, Niccoli L, Catanoso MG, Macchioni P, Pulsatelli L, et al. Treatment of refractory polymyalgia rheumatica with infliximab: a pilot study. J Rheumatol. 2003;30:760-3

3. Cantini F, Niccoli L, Salvarani C, Padula A, Olivieri I. Treatment of longstanding active giant cell arteritis with infliximab: report of 4 cases. Arthritis Rheum 2001;44:2933-5.

4. Catanoso MG, Macchioni PL, Boiardi L, Pipitone N, Salvarani C. Treatment of refractory polymyalgia rheumatica with etanercept: an open pilot study. Arthritis Rheum, in press.

5. Hernandez-Rodriguez J, Segarra M, Vilardell C, Sanchez M, Garcia- Martinez A, Esteban MJ, et al. Tissue production of pro-inflammatory cytokines (IL-1, TNF and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis. Rheumatology 2004; 43:294-301.

Conflict of Interest:

None declared

Response to Drs Salvarani and Hunder
Posted on July 5, 2007
Raashid A Luqmani
University of Oxford
Conflict of Interest: None Declared

I am grateful to Dr Salvarani and Professor Hunder for raising the issue that their studies of infliximab in PMR and GCA have not been designed to test a small treatment effect of the agent, above that achieved from corticosteroid alone. If there is only a small treatment effect, a cost benefit analysis is likely to conclude that infliximab does not have a significant role in the management of PMR or GCA. If on the other hand, it was demonstrated that severe complications such as sight loss in GCA could be prevented or that steroid toxicity could be avoided by using much lower doses of steroid, these would be more compelling reasons to reconsider the use of this agent in these diseases.

There is a separate question as to whether or not infliximab has a role in the management of patients who have relapsing or resistant disease where the authors point out that benefits have been seen, albeit in pilot studies. Reduction in IL-6 levels as a result of suppressing TNF and associated with clinical benefit would suggest that a more direct attack on IL-6 might be more logical especially since the persistence of IL-6 in temporal biopsies is predictive of disease persistence. There would certainly be support for a study looking at management of resistant PMR and GCA with anti-TNF therapy or indeed anti-IL-6 therapy.

It is possible that we may be able to identify patients who are likely to do badly at onset and stratify those for an anti-TNF or anti-IL-6 strategy. It is becoming more realistic to perform cytokine profiles in clinical practice in future therefore identifying those patients who are most likely to require more aggressive therapy and equally identifying patients who may benefit from much milder therapy, as shown in the cohort of patients in these two studies who benefited from relatively short duration corticosteroid.

Conflict of Interest:

None declared

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