POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS



















  • Reference: ACR 2012 Proposed PMR Criteria
ACR 2012 PMR Diagnostic Criteria
PMR diagnosis - ALL patients MUST have the following:
  • Age ≥ 50 years
  • Bilateral shoulder aching
  • Elevated ESR or C-reactive protein
If the above criteria are met, then the diagnosis is based on a scoring system with the criteria below. The score required for diagnosis differs on whether ultrasound (US) results are available.
  • Criteria without US - score of ≥ 4 establishes PMR diagnosis
  • Criteria with US - score of ≥ 5 establishes PMR diagnosis
Criteria Score
Morning stiffness for > 45 minutes 2
Hip pain or limited range of motion 1
Negative Rheumatoid factor or ACPA 2
Absence of other joint pain 1
When US results are available
At least 1 shoulder with subdeltoid bursitis and/or biceps tenosynovitis and/or glenohumeral synovitis (either posterior or axillary) and at least 1 hip with synovitis and/or trochanteric bursitis 1
Both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis 1


  • FDG - fluorodeoxyglucose
  • Reference [16]
ACR/EULAR 2022 Classification Criteria for Giant Cell Arteritis
These criteria should only be applied to patients who meet all of the following:
  • Age ≥ 50 years
  • Diagnosis of medium- or large-vessel vasculitis
  • Exclusion of diagnoses that mimic vasculitis

Sum the score from the 10 criteria below. A score ≥ 6 classifies the vasculitis as giant cell arteritis.
Clinical criteria
Finding / symptom Score
Morning stiffness in shoulders/neck 2
Sudden visual loss 3
Jaw or tongue claudication 2
New temporal headache 2
Scalp tenderness 2
Abnormal examination of the temporal artery (absent or diminished pulse, tenderness, or hardness) 2
Laboratory, imaging, and biopsy criteria
Maximum ESR ≥ 50 mm/hour or maximum CRP ≥ 10 mg/liter (prior to treatment initiation) 3
Positive temporal artery biopsy or halo sign on ultrasound 5
Bilateral axillary involvement defined as luminal damage (stenosis, occlusion, or aneurysm) on imaging 2
FDG-PET activity throughout the aorta 2

ACR/EULAR 2015 Polymyalgia Rheumatica Treatment Recommendations
Corticosteroids
  • Prednisone
    • Prednisone or prednisone equivalent is the recommended first-line treatment
    • Starting: 12.5 - 25 mg once daily
    • Initial tapering: taper to a dose of 10 mg/day within 4 - 8 weeks
    • Tapering after remission achieved: taper daily oral prednisone by 1 mg every 4 weeks (or by 1.25 mg decrements using schedules such as 10/7.5 mg on alternate days, etc) until discontinuation as long as remission is maintained
    • In case of relapse: increase oral prednisone to the pre-relapse dose and decrease it gradually (within 4–8 weeks) to the dose at which the relapse occurred
    • Duration: minimum of 12 months of treatment [13]
  • Methylprednisolone
    • Alternative to prednisone. May be appropriate when overall lower exposure to corticosteroids is desired.
    • Starting: 120 mg intramuscular every 3 weeks through week 9
    • Tapering: at week 12, give 100 mg and increase the dosing interval to every month. Reduce the dose by 20 mg every 12 weeks until week 48. Thereafter, reduce dose 20 mg every 16 weeks until discontinuation [13]
Methotrexate
  • Methotrexate may be considered in addition to corticosteroids in the following patients: disease relapse, high risk of relapse and/or prolonged therapy, high risk of corticosteroid-related adverse events, inadequate response to corticosteroids, development of corticosteroid-related adverse events
  • Dosing: 7.5 - 10 mg/week has been used in trials
  • See methotrexate for drug information
  • See Methotrexate vs Placebo in PMR below [13]
Exercise
  • The ACR/EULAR guidelines conditionally recommend considering an individualized exercise program for PMR patients aimed at the maintenance of muscle mass and function, and reducing risk of falls [13]


  • Reference [8,15]
2021 ACR/Vasculitis Foundation GCA treatment recommendations
Initial therapy
Patients with visual symptoms, vision loss, or critical cranial ischemia
  • High-dose IV pulse glucocorticoids followed by high-dose oral glucocorticoids with tocilizumab
  • Glucocorticoids with methotrexate or glucocorticoids alone may be considered in some cases
  • For patients with critical or flow-limiting involvement of the vertebral or carotid arteries, aspirin is recommended
    • High-dose IV pulse glucocorticoids: IV methylprednisolone 500 – 1,000 mg/day (adults) or 30 mg/kg/day (children; maximum 1,000 mg/day) or equivalent for 3– 5 days
    • High-dose oral glucocorticoids: prednisone 1 mg/kg/day up to 80 mg or equivalent

Patients without visual symptoms, vision loss, or critical cranial ischemia
  • High-dose oral glucocorticoids with tocilizumab
  • Glucocorticoids with methotrexate or glucocorticoids alone may be considered in some cases
    • High-dose oral glucocorticoids: prednisone 1 mg/kg/day up to 80 mg or equivalent
Clinical response
Remission achieved
  • Taper glucocorticoids. The ACR guidelines state that the duration of therapy should be based on individual response and preferences, and they do not give recommendations on tapering steroids. Recommendations from the British Society of Rheumatology do offer some guidance and are provided below (see BSR glucocorticoid recommendations).

Remission not achieved
  • Consider adding or changing non-glucocorticoid immunosppressive agent. For example, methotrexate or abatacept may be substituted for tocilizumab.






Tocilizumab vs Placebo in Glucocorticoid-Dependent PMR, JAMA (2022) [PubMed abstract]
  • The trial enrolled 101 patients with active PMR who were receiving glucocorticoids
Main inclusion criteria
  • PMR diagnosis by Chuang's criteria
  • CRP ≥ 10 mg/L or ESR ≥ 20 mm/hr
  • Glucocorticoid dependency
Main exclusion criteria
  • Possible GCA
  • Prednisone > 25 mg/day
  • Uncontrolled dyslipidemia
  • Uncontrolled hypertension
  • Immunosuppressant other than methotrexate
Baseline characteristics
  • Median age 68 years
  • Female sex - 66%
  • Median duration of PMR - 18 months
  • Median CRP - 0.9 mg/dl
  • Median ESR - 26 mm/hr
  • Median prednisone dose - 10 mg
  • Taking methotrexate - 31%
Randomized treatment groups
  • Group 1 (49 patients): Tocilizumab (8 mg/kg) IV every 4 weeks for 24 weeks
  • Group 2 (51 patients): Placebo
  • At each study visit after week 8 (weeks 12, 16, and 20), prednisone dosages greater than 10 mg per day were tapered by 5 mg. For dosages less than or equal to 10 mg per day, if the CRP PMR-AS was less than 10, the prednisone dosage was decreased by 2 mg every 2 weeks according to the investigator's evaluation of disease activity.
Primary outcome: Composite of low disease activity, defined as CRP PMR-AS (range, 0-100; higher scores indicate greater disease activity) less than 10, and either prednisone dosage less than or equal to 5 mg per day or prednisone dosage decrease by greater than or equal to 10 mg vs baseline at 24-week follow-up.
Results

Duration: 24 weeks
Outcome Tocilizumab Primary Comparisons
Primary outcome 67.3% 31.4% p<0.001
CRP PMR-AS score 7.5 14.9 p<0.001
Stopped prednisone 49% 19.6% p<0.001
Infection 47% 39% N/A
Headache 14% 2% N/A
Hyperlipidemia 12% 4% N/A
Cytopenia 8% 4% N/A
  • Average prednisone dose was 3.8 mg/day in the tocilizumab group and 6.1 mg/day in the placebo group.

Findings: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms.
Tocilizumab vs Placebo for Giant Cell Arteritis, NEJM (2017) [PubMed abstract]
  • The trial enrolled 251 patients with active giant cell arteritis
Main inclusion criteria
  • ≥ 50 years of age
  • Active giant-cell arteritis within 6 weeks before baseline
  • ESR > 30 mm/hour or CRP ≥ 1 mg/dL (including a presenting history of ESR> 50 mm/hour)
  • Cranial symptoms of GCA or symptoms of polymyalgia rheumatica
  • Evidence of GCA on imaging or temporal artery biopsy
Main exclusion criteria
  • Major ischemic event, related or unrelated to GCA, within 12 weeks of screening
  • History of GI disease (e.g. diverticulitis, Crohn's, ulcerative colitis) that might predispose a patient to perforations
  • Serum creatinine > 1.4 mg/dL
  • Total bilirubin > ULN
  • ALT or AST> 1.5 X ULN
Baseline characteristics
  • Average age - 69 years
  • Newly-diagnosed GCA - 48%, Relapsing GCA - 52%
  • Average duration of disease - 296 days
  • Symptoms of PR - 61%
  • Average ESR - 24 mm/hr
Randomized treatment groups
  • Group 1 (100 patients): Tocilizumab 162 mg SQ once weekly + 26-week prednisone taper
  • Group 2 (50 patients): Tocilizumab 162 mg SQ every other week + 26-week prednisone taper
  • Group 3 (50 patients): Placebo + 26-week prednisone taper
  • Group 4 (51 patients): Placebo + 52-week prednisone taper
  • Prednisone was initiated at a previously used dose or continued at current dose and then tapered weekly
Primary outcome: Rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper
Results

Duration: 52 weeks
Outcome Toc weekly Toc biweekly Placebo 26 Placebo 52 Comparisons
Primary outcome 56% 53% 14% 18% 1 or 2 vs 3: p<0.001
  • The incidence of adverse events was similar in all the trial groups, but fewer patients reported serious adverse events in the Tocilizumab weekly (15%) and Tocilizumab biweekly (14%) groups than in the Placebo 26 (22%) and Placebo 24 (25%) groups

Findings: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab.