Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

initial presentation

1st line – corticosteroid

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ACUTE
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initial presentation
1st line – 

corticosteroid

The mainstay of therapy is a low-dose corticosteroid as a single daily dose. Response in this dose range usually occurs within 24 to 72 hours. Failure of response should lead to re-evaluation of the diagnosis or to consideration of treatment resistance.

Corticosteroids should be continued until symptoms resolve and ESR/CRP normalizes (about 2 to 4 weeks). The minimum effective dose (i.e., 12.5 to 25 mg/day of prednisone or its equivalent) should be given. The dose should then be tapered to 10 mg/day of prednisone (or its equivalent) over 4 to 8 weeks. Tapering can then occur at a rate equivalent to 1 mg/month of prednisone.[45]

The duration of treatment is typically at least 1 year, and it is often longer, depending upon the patient's response.

Although not standard therapy, intramuscular methylprednisolone can be considered for patients who are poorly adherent to treatment.[45][46]

In all adults ages over 40 years taking prednisone ≥2.5 mg/day for over 3 months prophylaxis of corticosteroid induced osteoporosis (GIOP) is recommended with calcium and vitamin D supplementation.[47]​ Patients receiving long term corticosteroids should be assessed for fracture risk as soon as possible after starting treatments and every 1-2 years while corticosteroid treatment continues, any additional prophylactic treatment for GIOP should be stratified by the risk of fracture.​[47] See Osteoporosis: Management approach.​

Primary options

prednisone: 12.5 to 25 mg orally once daily initially, then taper to 10 mg once daily over 4-8 weeks, then taper by 1 mg/month thereafter

Secondary options

methylprednisolone: 120 mg intramuscularly every 3 weeks for 3 months then taper dose gradually, consult specialist for further guidance on dose

Consider – nonsteroidal anti-inflammatory drug (NSAID)

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ACUTE
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initial presentation
Consider – 

nonsteroidal anti-inflammatory drug (NSAID)

Treatment recommended for SOME patients in selected patient group

Concomitant use of NSAIDs and corticosteroids should be avoided whenever possible, to minimize the risk of gastrointestinal bleeding. For patients experiencing peripheral musculoskeletal symptoms during corticosteroid withdrawal NSAIDs may be used for a limited duration. Primary NSAID use for PMR related symptoms is not recommended.

Chronic use should be avoided due to serious adverse effects. The risk of gastrointestinal bleeding may be increased due to concurrent corticosteroid use. A proton-pump inhibitor (e.g., omeprazole) should be considered to prevent ulcer development.

Primary options

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

ibuprofen: 400-800 mg orally every 4-6 hours when required, maximum 3200 mg/day

2nd line – methotrexate

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ACUTE
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initial presentation
2nd line – 

methotrexate

Use of methotrexate is recommended for practitioners who are either experienced with its use or in consultation with such experienced practitioners. In particular, it should be considered in: individuals at high risk for relapse or prolonged therapy (female sex, high ESR [>40 mm/hour], and peripheral arthritis at diagnosis); patients who have relapsed; patients who have not had an adequate response to corticosteroids; patients for whom prolonged corticosteroid use is associated with significant adverse effects (i.e., osteoporosis, glaucoma, cataracts, diabetes); patients with comorbidities that could be exacerbated by corticosteroid therapy.[11][45][48]​​

When methotrexate is used as a corticosteroid-sparing agent, it should be continued until the corticosteroids can be tapered without the recurrence of PMR symptoms. There are no definitive guidelines regarding the tapering of methotrexate. However, once the corticosteroids have been successfully tapered, it would be reasonable to discontinue the methotrexate by tapering the dose over approximately 3 months.

A baseline CXR is recommended to evaluate for any underlying interstitial lung disease prior to starting treatment. If interstitial lung disease is present, methotrexate is usually not started. Any other significant pulmonary disease may be a relative contraindication to starting methotrexate.

Baseline CBC, liver function tests (LFTs), and hepatitis B and C serologies are recommended prior to initiating methotrexate. Any significant liver test abnormality, hematologic abnormality, history of hepatitis B or C infection, history of ongoing alcohol use, or history of a malignancy is a relative contraindication to methotrexate use.[49] The CBC, creatinine, and LFTs should be checked once per month with each dose increase. Once a stable dose has been established for 6 months without any adverse effects, these levels can be checked every 3 months.

Doses of 7.5 to 10 mg/week have been studied, although higher doses may be needed.[45]

Primary options

methotrexate: 7.5 mg orally once weekly on the same day of each week, increase by 2.5 mg/week increments every 2-3 months if required, maximum 20 mg/week

Plus – folic acid

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ACUTE
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initial presentation
Plus – 

folic acid

Treatment recommended for ALL patients in selected patient group

Indicated to decrease the risk of methotrexate adverse effects, particularly the risk of oral ulcers and bone marrow suppression.

Primary options

folic acid (vitamin B9): 1 mg orally once daily

3rd line – tocilizumab

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ACUTE
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initial presentation
3rd line – 

tocilizumab

There have been a few case reports of the use of tocilizumab in patients with contraindications to, or adverse events from corticosteroid treatment.[53][54] Randomized studies examining the use of tocilizumab in isolated PMR are lacking.

Tocilizumab may increase the risk of serious liver injury (e.g., acute liver failure, hepatitis). Measure aminotransferase (ALT) and aspartate aminotransferase (AST) levels before initiation and every 4-8 weeks during the first 6 months of treatment. After the first 6 months, levels can be monitored every 12 weeks. Initiation of treatment is not recommended in patients with ALT or AST higher than 5-times the upper limit of normal. Patients should be advised to seek help immediately if they experience signs and symptoms of liver injury.[56] Although tocilizumab has been approved in the US for use in giant cell arteritis, it is currently not approved for the treatment of isolated PMR.

Primary options

tocilizumab: consult specialist for guidance on dose

ONGOING

treatment-resistant or relapse or disease exacerbation

1st line – corticosteroid (increased dose)

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ONGOING
|
treatment-resistant or relapse or disease exacerbation
1st line – 

corticosteroid (increased dose)

Some patients are resistant to corticosteroid therapy, or may have significant PMR symptoms at night. In these patients the corticosteroids can be increased to twice-daily dosing in order to control symptoms and normalize ESR and CRP. Once this occurs, the dose can be tapered.

About 30% to 50% of patients experience relapses unrelated to the corticosteroid dose or taper rate, commonly within 2 years of diagnosis. In these cases, the corticosteroids are increased to the dose before the relapse occurred, with control of symptoms and normalization of the ESR and the CRP. Once the symptoms are controlled, the dose should be tapered over 4 to 8 weeks to the dose at which the relapse occurred. Tapering the dose at the rate of 1 mg/month prednisone equivalent can then resume if symptoms remain in remission.

Although there is no precise definition for relapse of PMR, the Delphi consensus approach among a panel of rheumatologists identified the following useful parameters for defining PMR relapse and remission: morning stiffness; pain in the neck, shoulders, upper arms, and pelvic girdle; shoulder pain on active and passive range of motion; limited shoulder elevation; hip synovitis; ESR and CRP; and dose of corticosteroids used for treatment.[50]

In all adults ages over 40 years taking prednisone ≥2.5 mg/day for over 3 months prophylaxis of corticosteroid induced osteoporosis (GIOP) is recommended with calcium and vitamin D supplementation.[47]​ Patients receiving long term corticosteroids should be assessed for fracture risk as soon as possible after starting treatment and every 1-2 years while corticosteroid treatment continues, any additional prophylactic treatment for GIOP should be stratified by the risk of fracture.​[47] See Osteoporosis: Management approach.​

Primary options

prednisone: consult specialist for guidance on dose

Secondary options

methylprednisolone: consult specialist for guidance on dose

Consider – methotrexate plus folic acid

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ONGOING
|
treatment-resistant or relapse or disease exacerbation
Consider – 

methotrexate plus folic acid

Treatment recommended for SOME patients in selected patient group

Use of methotrexate is recommended for practitioners who are either experienced with its use or in consultation with such experienced practitioners.

When methotrexate is used as a corticosteroid-sparing agent, it should be continued until the corticosteroids can be tapered without the recurrence of PMR symptoms. There are no definitive guidelines regarding the tapering of methotrexate. However, once the corticosteroids have been successfully tapered, it would be reasonable to discontinue the methotrexate by tapering the dose over approximately 3 months.

A baseline CXR is recommended to evaluate for any underlying interstitial lung disease prior to starting treatment. If interstitial lung disease is present, methotrexate is usually not started. Any other significant pulmonary disease may be a relative contraindication to starting methotrexate.

Baseline CBC, liver function tests, and hepatitis B and C serologies are recommended prior to initiating methotrexate. Any significant liver test abnormality, hematologic abnormality, history of hepatitis B or C infection, history of ongoing alcohol use, or history of a malignancy is a relative contraindication to methotrexate use.[49]

Doses of 7.5 to 10 mg/week have been studied, although higher doses may be needed.[45]

Folic acid is indicated to decrease the risk of methotrexate adverse effects, particularly the risk of oral ulcers and bone marrow suppression.

Primary options

methotrexate: 7.5 mg orally once weekly on the same day of each week, increase by 2.5 mg/week increments every 2-3 months if required, maximum 20 mg/week

and

folic acid (vitamin B9): 1 mg orally once daily

2nd line – tocilizumab or leflunomide

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ONGOING
|
treatment-resistant or relapse or disease exacerbation
2nd line – 

tocilizumab or leflunomide

Tocilizumab has been shown in case reports to be effective in treating PMR.[51][52] Tocilizumab can be considered for patients who are not responsive to glucocorticoids or when the glucocorticoid dose cannot be tapered because of recurrence. Randomized studies examining the use of tocilizumab in isolated PMR are lacking. One meta-analysis suggests tocilizumab may be more effective in combination with glucocorticoids.[55]

Tocilizumab may increase the risk of serious liver injury (e.g., acute liver failure, hepatitis). Measure aminotransferase (ALT) and aspartate aminotransferase (AST) levels before initiation and every 4-8 weeks during the first 6 months of treatment. After the first 6 months, levels can be monitored every 12 weeks. Initiation of treatment is not recommended in patients with ALT or AST higher than 5-times the upper limit of normal. Patients should be advised to seek help immediately if they experience signs and symptoms of liver injury.[56] Although it has been approved in the US for use in giant cell arteritis, it is currently not approved for the treatment of isolated PMR.

Leflunomide was also effective for relapsing/refractory PMR in one case series.[57] 

Primary options

tocilizumab: consult specialist for guidance on dose

OR

leflunomide: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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