Approach

The goal of treatment is to establish an inflammation-free and symptom-free state. The patient should ideally return to the prior baseline level of function with a normal ESR and/or CRP.

Corticosteroids

The mainstay of therapy is low-dose corticosteroids; response usually occurs within 24 to 72 hours. The corticosteroid dose is increased until complete symptom resolution and normalisation of the ESR and CRP. Failure of response should lead to re-evaluation of the diagnosis or to consideration of treatment resistance.

The lowest effective corticosteroid dose is recommended. In general, tapering of the dose should be individualised to the patient. However, it is recommended that once symptoms have resolved and inflammatory markers have normalised, the dose is tapered. Relapses should be treated by increasing the dose to the pre-relapse dose, and then slowly tapering the dose over 4 to 8 weeks to the dose at which the relapse occurred.[45]

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

In all adults over 40 years of age taking prednisolone ≥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 corticosteroid treatment, and every 1 to 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​.

Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids should be avoided to minimise the risk of gastrointestinal bleeding.

Withdrawal symptoms including arthralgias, malaise, and fatigue might be confused with recurrent PMR symptoms. Slow tapering of the corticosteroids over a 2- to 3-year period is often required to prevent relapses and symptom exacerbations.

Non-steroidal anti-inflammatory drugs

NSAIDs are not recommended for the treatment of PMR. They can be considered for short-term use for pain associated with other conditions (e.g., corticosteroid withdrawal symptoms).

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.

Methotrexate

The use of methotrexate should be considered early during the course of treatment on an individual basis. In particular, it should be considered in:[11][45]​​

  • Individuals at high risk for relapse or prolonged therapy (female sex, high ESR [>40 mm/hour], and peripheral arthritis at diagnosis)[48]

  • 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 which could be exacerbated by corticosteroid therapy.

Folic acid is used concomitantly to decrease the risk of methotrexate-associated adverse effects.

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

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.

Baseline FBC, liver function tests (LFTs), and hepatitis B and C serologies are also recommended prior to initiating methotrexate. Any significant liver test abnormality, haematological abnormality, history of hepatitis B or C infection, history of on-going alcohol use, or history of a malignancy is a relative contraindication to methotrexate use.[49] The FBC, 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.

Relapse or disease exacerbation

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 a dose that controls symptoms and normalises the ESR and CRP. Once the symptoms are controlled, tapering can resume.

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:[50]

  • 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

  • dose of corticosteroids used for treatment.

Treatment-resistant cases

The daily corticosteroid dose can be increased to twice daily dosing in order to control symptoms and normalise ESR and CRP. Once this occurs, the dose can be tapered.

Tocilizumab has been shown in case reports to be effective in treating PMR. An open-label phase-2a trial studied 10 patients with newly diagnosed PMR (corticosteroids for <1 month) treated with monthly tocilizumab for 1 year.[51] Corticosteroid-free relapse-free remission was achieved in 9 patients at 6 months, with 1 patient withdrawing; remission was sustained through the 15 months of the study. In a second study, 20 patients not treated with corticosteroids were treated with tocilizumab infusions every 3 months followed by oral prednisone.[52] After 6 months, the PMR activity scores had significantly decreased in all patients, prednisone doses were minimised, and PET-CT imaging showed improvement in inflammatory musculoskeletal changes.

Tocilizumab can be considered for patients who are not responsive to glucocorticoids or when the glucocorticoid dose cannot be tapered because of recurrence. It is also sometimes used for patients at initial presentation if they are unable to tolerate other treatments.[53][54] Randomised 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 tocilizumab 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]

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