The role of intravenous methylprednisolone pulses in the management of rheumatoid arthritis

M. D. Smith, P. J. Roberts-Thomson1 and M. J. Ahern

Rheumatology Unit, Repartriation General Hospital, Daws Road, Daw Park, South Australia and
1 Departments of Immunology and Rheumatology, Flinders Medical Centre, South Road, Bedford Park, South Australia, Australia.

SIR, We read with interest the letter by Dessein et al. [1] and can only agree that the potential benefits of intravenous methylprednisolone pulses in the management of rheumatoid arthritis (RA) are largely being ignored in the rheumatology community. This is somewhat surprising in view of the large amount of clinical and scientific study that has been published on this treatment. We have been studying this treatment for over 15 yr and have published extensively on its clinical benefits [26], the long-term effects on functional outcome [7], the effect on neutrophil trafficking into the joint [8] and the effect on the synovial fluid and membrane of RA patients [911]. We have also previously raised the issue of the role of pulse methylprednisolone treatment in the management plan for the patient with RA [12, 13].

We have demonstrated that this treatment has similar effects on the synovial membrane of RA patients to that seen with anti-tumour necrosis factor treatments [14], yet this treatment is far more available and cheaper than either Enbrel or Infliximab.

We would like to correct the authors on one mistake in their letter. The follow-up on the patients in our study [7] quoted in their letter was 32 and 67 months after participating in the 24-week, double-blind, placebo-controlled trial, not 32 and 67 weeks as stated in their letter.

It is therefore difficult to understand the apparent reluctance to use such a readily available and effective treatment, which is cheap and relatively free of significant adverse events in the management of RA patients, especially at an early stage in the initiation of treatment with disease-modifying anti-rheumatic drugs.

Notes

Correspondence to: M. D. Smith, Repatriation General Hospital, Division of Medicine, Daw Park, South Australia 5041, Australia. Back

Accepted 11 April 2000

References

  1. Dessein PH, Shipton EA, Budd K. Oral low-dose glucocorticosteroids as compared with intravenous methylprednisolone pulses in the treatment of rheumatoid arthritis. Rheumatology1999;38:1304–5.[Free Full Text]
  2. Bertouch JV, Roberts-Thomson PJ, Smith MD, Woodruff TG, Brooks PM, Bradley J. Methylprednisolone infusion therapy in rheumatoid arthritis. The effect on synovial fluid lymphocyte subsets and inflammatory indices. Arthritis Rheum1986;29:32–8.[ISI][Medline]
  3. Smith MD, Bertouch JV, Smith AM, Weatherall M, Ahern MJ, Brooks PM, Roberts-Thomson PJ. The clinical and immunological effects of pulse methylprednisolone therapy in rheumatoid arthritis. 1. Clinical effects. J Rheumatol1988;15:229–32.[ISI][Medline]
  4. Smith MD, Ahern MJ, Brooks PM, Roberts-Thomson PJ. The clinical and immunological effects of pulse methylprednisolone therapy in rheumatoid arthritis. 2. Effects on immune and inflammatory indices in peripheral blood. J Rheumatol1988;15:233–7.[ISI][Medline]
  5. Smith MD, Ahern MJ, Brooks PM, Roberts-Thomson PJ. The clinical and immunological effects of pulse methylprednisolone therapy in rheumatoid arthritis. 3. Effects on immune and inflammatory indices in synovial fluid. J Rheumatol1988;15:238–41.[ISI][Medline]
  6. Wong CS, Champion G, Smith MD, Soden M, Wetherall M, Geddes RA et al. Does steroid pulsing influence the efficacy and toxicity of chrysotherapy? A double blind placebo controlled study. Ann Rheum Dis1990;49:370–2.[Abstract]
  7. Heytman M, Ahern M, Smith MD, Roberts-Thomson PJ. The long term effects of pulsed corticosteroids on the efficacy and toxicity of chrysotherapy in rheumatoid arthritis. J Rheumatology1994;21:435–41.[ISI][Medline]
  8. Youssef PP, Cormack J, Evill C, Peter DJ, Roberts-Thomson PJ, Ahern MJ et al. Neutrophil trafficking into inflamed joints in rheumatoid arthritis and the effect of methylprednisolone. Arthritis Rheum1996;39:216–25.[ISI][Medline]
  9. Youssef PP, Roberts-Thomson PJ, Ahern MJ, Smith MD. Pulse methylprednisolone in rheumatoid arthritis: Effects on peripheral blood and synovial fluid neutrophil surface phenotype. J Rheumatol1995;23:2065–71.
  10. Youssef PP, Triantafillou S, Parker A, Coleman M, Roberts-Thomson PJ, Ahern MJ et al. Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Arthritis Rheum1996;39:1970–9.[ISI][Medline]
  11. Youssef PP, Triantafillou S, Parker A, Gamble J, Haynes D, Roberts-Thomson PJ et al. Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid and the synovial membrane in rheumatoid arthritis. Arthritis Rheum1997;40:1400–8.[ISI][Medline]
  12. Smith MD. Pulse therapy in RA. Ann Rheum Dis1988;47:880.[ISI]
  13. Smith MD, Ahern MJ, Roberts-Thomson PJ. Pulse methylprednisolone therapy in rheumatoid arthritis. Unproven therapy, unjustified therapy or effective adjunctive therapy? Ann Rheum Dis1990;49:265–7.[ISI][Medline]
  14. Roberts-Thomson PJ, Smith MD, Ahern MJ. Similarities in the mechanisms of action of pulse corticosteroids and anti-tumor necrosis factor {alpha} therapy in rheumatoid arthritis. Arthritis Rheum1998;41:564–5.[ISI][Medline]

 

Reply

P. H. Dessein, E. A. Shipton1, K. Budd2 and A. E. Stanwix3

Rheumatology Unit, Milpark Hospital,
1 Department of Anaesthesiology, Baragwanath Hospital and
2 Department of Rheumatology, Johannesburg Hospital, University of the Witwatersrand, Johannesburg, South Africa and
3 Department of Anaesthesia, University of Leeds, Leeds, UK.

We would like to thank Smith et al. [1] for their interest in our letter summarizing recently reported evidence in keeping with an underestimation of the role of methylprednisolone (MP) pulses as bridge therapy in rheumatoid arthritis (RA) [2]. Smith and colleagues refer to their extensive previous work on the beneficial effects of intravenous MP pulses on clinical features and the molecular and cellular processes in RA. We believe two further issues are worth considering in the delineation of the role of MP pulses and other glucocorticoid regimens in future studies in this disease.

While most investigators have used relatively high doses of MP, this may not be universally indicated. Doses as low as 120 mg MP, given i.m., were reported to be of benefit as bridge therapy in RA [3]. In a recent 6-month study, the use of 80–140 mg MP given intra-articularly or i.m. was associated with an abortive effect on RA of <= 12 weeks' duration in 50% of such patients [4]. This is similar to what was previously reported by Sternberg et al. [5] in an experimental model of arthritis. Future studies addressing the optimal doses of MP in the individual patient, for example by tailoring to disease activity, seem warranted.

The findings reported by Sternberg et al. [5] and Green et al. [4] are in keeping with the paradigm in which hypothalamic–pituitary–adrenal (HPA) axis hypofunction mediates the development and persistence of RA. Indeed, decreased dehydroepiandrosterone sulphate (DHEAS) concentration, a most sensitive indicator of adrenocortical hypofunction, constitutes a recently identified risk factor for RA, and early RA patients experience inappropriately normal serum cortisol levels for the degree of ongoing inflammation [6]. Also, the dynamic HPA axis responses to stressors may be more important than basal cortisol levels in immune homeostasis [7]. This suggests that the role of physiological doses of glucocorticoids (e.g. <5 mg prednisolone daily) [8, 9], which may enhance HPA axis responsiveness [10], needs further clarification in controlled studies.

Notes

Correspondence to: P. Dessein, P.O. Box 1012, Melville 2109, Johannesburg, South Africa. Back

References

  1. Smith MD, Roberts-Thomson PJ, Ahern MJ. The role of intravenous methylprednisolone pulses in the management of rheumatoid arthritis. Rheumatology2000;39:1296.[Free Full Text]
  2. Dessein PH, Shipton EA, Budd K. Oral low-dose glucocorticosteroids as compared with intravenous methylprednisolone pulses in the treatment of rheumatoid arthritis. Rheumatology1999;38:1304–5.[Free Full Text]
  3. Choy EH, Kingsley GH, Corkill MM, Panayi GS. Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy. Br J Rheumatol1993;32:734–9.[ISI][Medline]
  4. Green M, Marzo-Ortega H, McGonagle D et al. Persistence of mild, early inflammatory arthritis. Arthritis Rheum1999;42:2184–8.[ISI][Medline]
  5. Sternberg EM, Hill JM, Chrousos GP et al. Inflammatory mediator-induced hypothalamic–pituitary–adrenal axis activation is defective in streptococcal cell wall arthritis susceptible Lewis rats. Proc Natl Acad Sci USA1989;86:2374–8.[Abstract]
  6. Masi AT, Bijlsma JWJ, Chikanza IC, Pitzalis C, Cutolo M. Neuroendocrine, immunologic, and microvascular systems interactions in rheumatoid arthritis: physiopathogenetic and therapeutic perspectives. Semin Arthritis Rheum1999;29:65–81.[ISI][Medline]
  7. Wickens T, De Rijk R. Glucocorticoids and immune function: unknown dimensions and new frontiers. Immunol Today1997;18:418–23.[ISI][Medline]
  8. Jefferies WM, Cleveland MD. Low-dosage glucocorticoid therapy. Arch Intern Med1967;119:265–78.[ISI][Medline]
  9. Fiechtner JJ, Miller DR, Sternberg VI. Control of rheumatoid arthritis with low-dose prednisolone: a patient-initiated flare-response regimen. Arthritis Rheum1991;34(Suppl.):S128.
  10. Jefferies WM. Safe uses of cortisol. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1996.
Accepted 11 April 2000