Polymyalgia Rheumatica Giant-Cell Arteritis

Polymyalgia Rheumatica and Giant-Cell Arteritis

1 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

Polymyalgia Rheumatica Giant-Cell Arteritis John G. Hanly, MD, MRCPI, FRCPC Date of Revision: December 2013

Introduction

Polymyalgia rheumatica (PMR) and giant-cell arteritis (GCA) are related conditions that affect older individuals and may reflect 2 ends of a spectrum of the same disease. PMR is characterized by aching and stiffness in the muscle groups of the neck, pectoral and pelvic girdles and thighs. The prevalence approaches 1% of people over the age of 50,1,2 and the lifetime risk of developing the disease has been estimated at 2.4% for women and 1.7% for men.3 GCA is a chronic vasculitis of large and medium-sized arteries with a predominance for the cranial branches of the arteries originating from the aortic arch. Thus, headache, jaw claudication and visual loss are common presentations. GCA is less frequent than PMR and affects approximately 0.2% of people 50 years of age and older.1,4 Both conditions are twofold more frequent in women than in men. There is a clear association between PMR and GCA. Approximately 16–21% of patients with PMR will develop GCA concurrently or subsequent to the diagnosis of PMR;1,2,5 conversely 40–60% of patients with GCA will develop symptoms of PMR. Although the etiology of both conditions is unknown, PMR is characterized pathologically by low grade synovitis of the proximal joints, while the hallmark of GCA is granulomatous inflammation with giant cells of affected arterial walls. Both conditions may be associated with systemic clinical manifestations.

Goals of Therapy

Eliminate symptoms of musculoskeletal pain and stiffness and associated malaise Restore function

Relieve symptoms due to GCA and prevent permanent visual loss Minimize the frequency and severity of corticosteroid toxicity

Investigations

The value of a thorough history and physical examination cannot be overemphasized. PMR and GCA are clinical diagnoses. Other than a positive temporal artery biopsy there are no laboratory tests that are specific for either disease. The diagnostic approach is outlined in Table 1 and Figure 1.

History

Patients with PMR typically present with the following characteristics: Significant proximal muscle discomfort, especially around the shoulders, across the neck, and in the buttocks and thighs. The pain is generally severe and usually interferes with activities of daily living. Many patients describe an acute onset and can pinpoint the start of their symptoms to a specific day.

Musculoskeletal morning stiffness lasting for hours is a prominent feature. Symptoms tend to worsen through the night, and movement during sleep causes discomfort severe enough to wake the patient. Systemic symptoms such as fever, malaise, anorexia and fatigue may be present in one-third of patients.8 Patients with GCA most frequently present with the following characteristics: Headache and scalp tenderness in the temporal or occipital areas, claudication of the jaw or tongue and partial or complete monocular visual loss which may affect the contralateral eye within 2 weeks even after starting corticosteroid therapy.

Additional distinct clinical presentations may occur based upon the pattern of vascular involvement and the degree of systemic symptoms.9 For example, involvement of large vessels such as the branches of the aortic arch, similar to that seen in Takayasu's arteritis, may occur in up to 15% of cases and is manifested by audible bruits and upper limb claudication. The treatment and outcome is comparable to GCA without large vessel involvement.10

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

2 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

Systemic symptoms, including fever, occur in up to 50% of cases.

A recognized late complication of GCA is a 17-fold increase in thoracic aortic aneurysm.11

Patients who present with PMR should be questioned specifically about symptoms of GCA.

Physical Examination

Patients with suspected PMR: The physical findings in PMR are nonspecific and usually reveal a reduction in range of motion of the neck and shoulders. Large and small joint synovitis may be present but is unusual in locations distal to the wrist and ankle. Severe swelling with pitting edema over the dorsum of both hands and feet may also occur and forms a distinct clinical subset.12,13 Proximal muscle tenderness may be present but muscle weakness, although difficult to assess due to pain, is not a predominant feature of PMR. Patients with suspected GCA: Diminished or absent temporal artery pulsation and associated scalp tenderness, coupled with an appropriate history, is suggestive of GCA. Funduscopic findings related to GCA include optic neuritis with pallor and edema of the optic disc, cotton-wool patches and small hemorrhages.

Laboratory Tests

Patients with suspected PMR: A rapid erythrocyte sedimentation rate (ESR) and elevated levels of C-reactive protein (CRP) are usually present. However, 5–6% of patients with PMR and GCA will have a normal ESR14,15 although in the majority of such cases the CRP is elevated.14 Anemia and/or thrombocytosis may also be found in patients presenting with PMR or GCA.

A number of conditions must be considered in the differential diagnosis of PMR (Table 1) although GCA can usually be readily distinguished from other forms of vasculitis. Patients with suspected GCA: See laboratory tests for PMR above.

Temporal artery biopsy is indicated only if there is a clinical suspicion of GCA and is not routinely recommended in patients who present with isolated PMR. Due to patchy involvement of affected vessels, a normal biopsy does not exclude the diagnosis. Thus, even when up to 5 cm of bilateral temporal arteries are sampled, 9% of suspected cases have normal biopsies.16,17,18,19 More recent studies have suggested that performing bilateral temporal artery biopsies increases the diagnostic yield by 1–12.7%.20,21 Corticosteroid therapy should not be withheld while awaiting the result of a temporal artery biopsy. This biopsy can still show changes of arteritis when performed up to 4 weeks following the commencement of corticosteroid therapy.22,23 The diagnostic approach is outlined in Figure 1.

Table 1: Differential Diagnosis of Polymyalgia Rheumatica (PMR) Diagnosis Myositis

Features Differentiating Condition From PMR Muscle weakness on physical examination

Elevated CPK

Abnormalities on EMG and muscle biopsy Fibromyalgia

Usually seen in younger patients

Widespread pain and tenderness at a significant number of soft tissue sites not limited to the shoulders and hips Normal ESR and CRP

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

3 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

Diagnosis

Features Differentiating Condition From PMR

Rheumatoid Arthritis

Synovitis distal to the wrist and ankle Seropositivity for RF

Consider anti-CCP antibodies if RF negative

Inadequate response to low-dose prednisone therapy Radiographic erosions Malignancy

No association between malignancy and PMR6 or GCA7, but some malignancies can mimic PMR. Investigate further as indicated by clinical exam and laboratory evaluation or if lack of response to conventional treatment.

Abbreviations: anti-CCP = anti-cyclic citrullinated peptide; CPK = creatine phosphokinase; CRP = C-reactive protein; EMG = electromyography; ESR = erythrocyte sedimentation rate; RF = rheumatoid factor

Polymyalgia Rheumatica (PMR)

Therapeutic Choices

Pharmacologic Choices Corticosteroids Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally ineffective or provide only partial improvement of symptoms in patients with PMR. Thus, systemic corticosteroids are the cornerstone of therapy. Prednisone 10–20 mg/day results in rapid and sustained clinical improvement8 (Table 2). Substantial or complete resolution of symptoms occurs within days. In fact, the diagnosis of PMR should be reconsidered if symptoms fail to improve significantly after 1 week of corticosteroid therapy.24 Most patients require 1–2 years of therapy, although 30–50% will experience exacerbations over this period.25 Some patients require corticosteroids for 5–10 years26 or indefinitely. For managing long-term corticosteroid therapy, see Prevention of Corticosteroid Toxicity.

Immunomodulators and Biologic Response Modifiers Methotrexate and azathioprine have been used in the treatment of PMR primarily to minimize corticosteroid exposure. However, studies have yielded conflicting results.27,28 Only 1 placebo-controlled study of methotrexate has shown benefit in patients with PMR.29 These drugs should be considered only in patients with significant corticosteroid toxicity, those unable to wean below 7.5 mg of prednisone daily and/or in patients with frequent relapses. The initial studies of biologic therapies such as infliximab30 and etanercept31,32 in steroid-resistant cases provided encouraging results, supported by a recent literature review.33 However, controlled studies of infliximab did not confirm benefit in the treatment of either PMR or GCA.34,35

Giant-Cell Arteritis (GCA)

Therapeutic Choices

Pharmacologic Choices Corticosteroids

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

4 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

GCA requires higher doses of corticosteroids, with an initial dose of 40–60 mg of prednisone daily.36 Alternate-day corticosteroid dosing to reduce the risk of adverse effects is not recommended, as it is associated with a higher relapse rate.37,38 Although the infusion of large doses of methylprednisolone (1000 mg daily for 3 days) has been used for the treatment of patients with impending visual loss, there is no evidence that this approach is more effective than oral prednisone.39 The chances of vision loss are reduced by prompt diagnosis and treatment20 but once vision loss occurs, corticosteroids will not usually reverse it. Most patients require 1–2 years of therapy, although 30–50% will experience exacerbations over this period.25,40 Some patients require corticosteroids for 5–10 years26,40 or indefinitely.41 For managing long-term corticosteroid therapy, see Prevention of Corticosteroid Toxicity.

Antiplatelet Agents Two retrospective studies suggest that patients who were receiving ASA (81–100 mg/day) prior to the diagnosis of giant-cell arteritis (GCA) had a lower risk of developing blindness following diagnosis of GCA.42,43 Therefore, in addition to prednisone, consider low-dose ASA therapy immediately following diagnosis of GCA [Evidence: SORT C].36 Although there are no data to suggest a recommended duration of ASA therapy, it is reasonable to continue for 4–6 weeks until the clinical and laboratory indicators of systemic inflammation have normalized and the risk of vision loss has abated. Cytoprotection with a proton pump inhibitor or misoprostol during concomitant prednisone and ASA therapy may reduce the risk of GI toxicity.44

Immunomodulators and Biologic Response Modifiers Two out of 3 placebo-controlled studies45,46,47 of methotrexate did not detect a statistically significant benefit in patients with GCA. However, a meta-analysis of the data from the same 3 studies found that adjunctive therapy with methotrexate lowered the risk of relapse and reduced exposure to corticosteroids.48 These drugs should be considered only in patients with significant corticosteroid toxicity, those unable to wean below 7.5 mg of prednisone daily and/or in patients with frequent relapses. A small controlled study of 17 patients suggested that the addition of etanercept in the treatment of patients with GCA resulted in lower cumulative doses of corticosteroids.49 Leflunomide,50 rituximab50 and tocilizumab50,51,52 may be considered in resistant cases. Consult a rheumatologist for initiation of an immunosuppressive or biologic agent.

Prevention of Corticosteroid Toxicity

.....

Since corticosteroids are associated with significant side effects, the lowest dose of corticosteroid needed to control symptoms should be used for the shortest period of time possible in order to minimize toxicity. Treatment with prednisone doses greater than 7.5 mg daily for more than 3 months has been associated with significant bone loss. Bisphosphonates prevent the bone loss associated with corticosteroid use and should be prescribed in patients with PMR or GCA commencing corticosteroid therapy (see Osteoporosis).53 Weight-bearing exercise, calcium (1200 mg total intake daily, preferably through dietary intake) and vitamin D (800–2000 IU daily) also reduce the risk of osteoporosis and should be prescribed in conjunction with bisphosphonates.

Therapeutic Tips

Prompt diagnosis and initiation of corticosteroid therapy is critical for the prevention of vision loss in patients with giant-cell arteritis. Treatment should not be delayed while awaiting a temporal artery biopsy which can still be positive up to 4 weeks after the initiation of corticosteroid therapy. Patients may report a transient increase in musculoskeletal symptoms after each corticosteroid dose reduction. These symptoms usually subside spontaneously over the ensuing week and do not necessarily represent a disease flare.

The ESR and CRP usually parallel disease activity in patients with PMR and GCA. These tests can be used to confirm the clinical suspicion of a disease flare but should not be used in isolation to make treatment decisions.

Reduction in shoulder range of motion may occur in some patients with PMR due to a localized rotator cuff tendonitis or capsulitis. This is more likely to occur when there has been a delay in diagnosis and initiation of therapy. A local corticosteroid injection (e.g., methylprednisolone acetate) of the subacromial bursa or glenohumeral joint is often helpful.

Algorithm

Figure 1: Diagnostic Approach in Patients with Suspected Polymyalgia Rheumatica (PMR) and Giant-Cell Arteritis (GCA)

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

5 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

Abbreviations: CBC = complete blood count; CPK = creatine phosphokinase; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate

Drug Table Table 2: Drug Therapy of Polymyalgia Rheumatica and Giant-Cell Arteritis Class

Drug

Dosage

Antiplatelet Agents

ASA Aspirin, Coated Aspirin, Entrophen, generics

GCA: 81 mg daily po, starting immediately following diagnosis.

Corticosteroids

prednison e generics

PMR: 15 mg daily po × 2 wk. Taper as follows: 12.5 mg daily po × 2 wk, 10 mg daily po × 4 wk, then decrease daily prednisone dose by 1 mg each month until completion

GCA: 40–60 mg daily po × 4 wk. Taper as follows:

Adverse Effects

Drug Interactions

Comments

Costa

Increased risk of bleeding when coadministered with anticoagulants, corticosteroids, NSAIDs and SSRIs.

Not a Health Canada–approved indication. Cytoprotection with a proton pump inhibitor or misoprostol during concomitant prednisone and ASA therapy may reduce the risk of GI toxicity.

$

Acne, glucose intolerance, weight gain, mood swings and agitation, cataracts, myopathy, hypertension, osteoporosis, aseptic necrosis of large joints, adrenal suppression, increased susceptibility to infection.

Barbiturates, phenytoin and rifampin decrease corticosteroid effect.

Avoid alternate-day corticosteroid dosing as it is associated with a higher rate of relapse.37,38 Ensure regular clinical assessments to look for recurrence of the original symptoms while concurrently checking CBC, ESR and CRP during the prednisone taper. An isolated rise in ESR or CRP is usually not sufficient

$

Gastritis, gastric/duodenal ulceration (rarely bronchospasm). Nausea, vomiting, GI hemorrhage, tinnitus, vertigo, hypersensitivity.

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

6 of 8

Class

Drug

Dosage decrease daily dose by 5 mg each wk until the dose is 10 mg daily. Then taper the daily dose more gradually by 1 mg each month until completion

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057 Adverse Effects

Drug Interactions

Comments

Costa

justification to increase the dose of corticosteroids. If a disease flare does occur, increase the dose of prednisone to the lowest level that was previously effective in controlling the disease. Maintain at that level for 1 month, then taper as before.

Immunosuppressive agents may be required in some cases. a

Cost of 30-day supply; includes drug cost only.

Abbreviations: CBC = complete blood count; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; GCA = giant-cell arteritis; PMR = polymyalgia rheumatica Legend:

$ < $ 10

Suggested Readings

Cantini F, Niccoli L, Nannini C et al. Diagnosis and treatment of giant cell arteritis. Drugs Aging 2008;25(4):281-97. Caylor TL, Perkins A. Recognition and management of polymyalgia rheumatica and giant cell arteritis. Am Fam Physician 2013;88(10):676-84. Dasgupta B, Borg FA, Hassan N et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology (Oxford) 2010;49(8):1594-7. Dasgupta B, Borg FA, Hassan N et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology (Oxford) 2010;49(1):186-90. Kermani TA, Warrington KJ. Polymyalgia rheumatica. Lancet 2013;281(9860):63-72.

References 1. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum 2009;61(10):1454-61. 2. Salvarani C, Gabriel SE, O'Fallon WM et al. Epidemiology of polymyalgia rheumatica in Olmsted County, Minnesota, 1970-1991. Arthritis Rheum 1995;38(3):369-73. 3. Crowson CS, Matteson EL, Myasoedova E et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum 2011;63(3):633-9. 4. Salvarani C, Gabriel SE, O'Fallon WM et al. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med 1995;123(3):192-4. 5. Franzen P, Sutinen S, von Knorring J. Giant cell arteritis and polymyalgia rheumatica in a region of Finland: an epidemiologic, clinical and pathologic study, 1984-1988. J Rheumatol 1992;19(2):273-6. 6. Myklebust G, Wilsgaard T, Jacobsen BK et al. No increased frequency of malignant neoplasms in polymyalgia rheumatica and temporal arteritis. A prospective longitudinal study of 398 cases and matched population controls. J Rheumatol 2002;29(10):2143-7.

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

7 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

7. Kermani TA, Schafer VS, Crowson CS et al. Malignancy risk in patients with giant cell arteritis: a population-based cohort study. Arthritis Care Res (Hoboken) 2010;62(2):149-54. 8. Salvarani C, Cantini F, Boiardi L et al. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med 2002;347(4):261-71. 9. Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatica. Ann Intern Med 2003;139(6):505-15. 10. Schmidt WA, Moll A, Seifert A et al. Prognosis of large-vessel giant cell arteritis. Rheumatology (Oxford) 2008;47(9):1406-8. 11. Evans JM, O'Fallon WM, Hunder GG. Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis. A population-based study. Ann Intern Med 1995;122(7):502-7. 12. Oide T, Ohara S, Oguchi K et al. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in Nagano, Japan: clinical, radiological, and cytokine studies of 13 patients. Clin Exp Rheumatol 2004;22(1):91-8. 13. Queiro R. RS3PE syndrome: a clinical and immunogenetical study. Rheumatol Int 2004;24(2):103-5. 14. Cantini F, Salvarani C, Olivieri I et al. Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study. Semin Arthritis Rheum 2000;30(1):17-24. 15. Salvarani C, Hunder GG. Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurrence in a population-based study. Arthritis Rheum 2001;45(2):140-5. 16. Hall S, Persellin S, Lie JT et al. The therapeutic impact of temporal artery biopsy. Lancet 1983;2(8361):1217-20. 17. Klein RG, Campbell RJ, Hunder GG et al. Skip lesions in temporal arteritis. Mayo Clin Proc 1976;51(8):504-10. 18. Gonzalez-Gay MA, Garcia-Porrua C, Llorca J et al. Biopsy-negative giant cell arteritis: clinical spectrum and predictive factors for positive temporal artery biopsy. Semin Arthritis Rheum 2001;30(4):249-56. 19. Hedges TR, Gieger GL, Albert DM. The clinical value of negative temporal artery biopsy specimens. Arch Ophthalmol 1983;101(8):1251-4. 20. Nordborg E, Nordborg C. Giant cell arteritis: strategies in diagnosis and treatment. Curr Opin Rheumatol 2004;16(1):25-30. 21. Breuer GS, Nesher G, Nesher R. Rate of discordant findings in bilateral temporal artery biopsy to diagnose giant cell arteritis. J Rheumatol 2009;36(4):794-6. 22. Achkar AA, Lie JT, Hunder GG et al. How does previous corticosteroid treatment affect the biopsy findings in giant cell (temporal) arteritis? Ann Intern Med 1994;120(12):987-92. 23. Ray-Chaudhuri N, Kine DA, Tijani SO et al. Effect of prior steroid treatment on temporal artery biopsy findings in giant cell arteritis. Br J Ophthalmol 2002;86(5):530-2. 24. Dasgupta B, Borg FA, Hassan N et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology (Oxford) 2010;49(1):186-90. 25. Salvarani C, Macchioni PL, Tartoni PL et al. Polymyalgia rheumatica and giant cell arteritis: a 5-year epidemiologic and clinical study in Reggio Emilia, Italy. Clin Exp Rheumatol 1987;5(3):205-15. 26. Bengtsson BA, Malmvall BE. Prognosis of giant cell arteritis including temporal arteritis and polymyalgia rheumatica. A follow-up study on ninety patients treated with corticosteroids. Acta Med Scand 1981;209(5):337-45. 27. De Silva M, Hazleman BL. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study. Ann Rheum Dis 1986;45(2):136-8. 28. Ferraccioli G, Salaffi F, De Vita S et al. Methotrexate in polymyalgia rheumatica: preliminary results of an open, randomized study. J Rheumatol 1996;23(4):624-8. 29. Caporali R, Cimmino MA, Ferraccioli G et al. Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2004;141(7):493-500. 30. Salvarani C, Cantini F, Niccoli L et al. Treatment of refractory polymyalgia rheumatica with infliximab: a pilot study. J Rheumatol 2003;30(4):760-3. 31. Tan AL, Holdsworth J, Pease C et al. Successful treatment of resistant giant cell arteritis with etanercept. Ann Rheum Dis 2003;62(4):373-4. 32. Catanoso MG, Macchioni P, Boiardi L et al. Treatment of refractory polymyalgia rheumatica with etanercept: an open pilot study. Arthritis Rheum 2007;57(8):1514-9. 33. Aikawa NE, Pereira RM, Lage L et al. Anti-TNF therapy for polymyalgia rheumatica: report of 99 cases and review of the literature. Clin Rheumatol 2012;31(3):575-9. 34. Salvarani C, Macchioni P, Manzini C et al. Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial. Ann Intern Med 2007;146(9):631-9. 35. Hoffman GS, Cid MC, Rendt-Zagar KE et al. Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med 2007;146(9):621-30. 36. Dasgupta B, Borg FA, Hassan N et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology (Oxford) 2010;49(8):1594-7. 37. Bengtsson BA, Malmvall BE. An alternate-day corticosteroid regimen in maintenance therapy of giant cell arteritis. Acta Med Scand 1981;209(5):347-50. 38. Hunder GG, Sheps SG, Allen GL et al. Daily and alternate-day corticosteroid regimens in treatment of giant cell arteritis: comparison in a prospective study. Ann Intern Med 1975;82(5):613-8.

02-Mar-16 9:39 PM

Polymyalgia Rheumatica and Giant-Cell Arteritis

8 of 8

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0057

39. Hayreh SS, Zimmerman B. Management of giant cell arteritis. Our 27-year clinical study: new light on old controversies. Ophthalmologica 2003;217(4):239-59. 40. Andersson R, Malmvall BE, Bengtsson BA. Long-term corticosteroid treatment in giant cell arteritis. Acta Med Scand 1986;220(5):465-9. 41. Gonzalez-Gay MA, Blanco R, Rodriguez-Valverde V et al. Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment. Arthritis Rheum 1998;41(8):1497-504. 42. Nesher G, Berkun Y, Mates M et al. Low-dose aspirin and prevention of cranial ischemic complications in giant cell arteritis. Arthritis Rheum 2004;50(4):1332-7. 43. Lee MS, Smith SD, Galor A et al. Antiplatelet and anticoagulant therapy in patients with giant cell arteritis. Arthritis Rheum 2006;54(10):3306-9. 44. Lanza FL, Chan FK, Quigley EM et al. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009;104(3):728-38. 45. Hoffman GS, Cid MC, Hellmann DB et al. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum 2002;46(5):1309-18. 46. Spiera RF, Mitnick HJ, Kupersmith M et al. A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA). Clin Exp Rheumatol 2001;19(5):495-501. 47. Jover JA, Hernandez-Garcia C, Morado IC et al. Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001;134(2):106-14. 48. Mahr AD, Jover JA, Spiera RF et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 2007;56(8):2789-97. 49. Martínez-Taboada VM, Rodríguez-Valverde V, Carreno L et al. A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects. Ann Rheum Dis 2008;67(5):625-30. 50. Unizony S, Stone JH, Stone JR. New treatment strategies in large-vessel vasculitis. Curr Opin Rheumatol 2013;25(1):3-9. 51. Isik M, Kilic L, Dogan I et al. Tocilizumab for giant cell arteritis: an amazing result. Rheumatol Int 2013;33(11):2961-2. 52. Unizony S, Arias-Urdaneta L, Miloslavksy E et al. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken) 2012;64(11):1720-9. 53. Grossman JM, Gordon R, Ranganath VK et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 2010;62(11):1515-26. CPhA assumes no responsibility for or liability in connection with the use of this information. For clinical use only and not intended for for use by patients. Once printed there is no quarantee the information is up-to-date. [Printed on: 03-02-2016 09:39 PM] RxTx, Compendium of Therapeutic Choices © Canadian Pharmacists Association, 2016. All rights reserved

02-Mar-16 9:39 PM