Tocilizumab improves GCA outcomes in patients with polymyalgia, cranial symptoms
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Tocilizumab improves outcomes in patients with giant cell arteritis who present with polymyalgia rheumatica symptoms only, cranial symptoms only or both at baseline, according to data published in Seminars in Arthritis & Rheumatism.
“Giant cell arteritis is a heterogeneous disorder with a variety of recognized clinical presentations,” Robert Spiera, MD, of the Hospital for Special Surgery in New York, told Healio Rheumatology. “Some patients present with cranial ischemic symptoms such as severe headaches or visual loss. Others can present primarily with systemic complaints related to their underlying inflammatory state including prominent polymyalgia rheumatica-like symptoms.”
“Some of those patients have cranial symptoms as well, but some do not, and there is a recognized subtype of patients with ‘large vessel vasculitis’ in whom inflammation is recognized in the aorta or its major branches but without localizing cranial complaints,” he added. “In the GiACTA trial, tocilizumab was demonstrated to be effective in affording disease control and having a significant steroid-sparing benefit in GCA. The trial included patients with these different presenting features.”
To assess the efficacy of tocilizumab (Actemra, Genentech) in patients with GCA with polymyalgia rheumatica or cranial symptoms, or both, Spiera and colleagues conducted a post hoc analysis of data from the GiACTA trial. This randomized, double-blind, placebo-controlled trial enrolled 250 adults aged 50 years and older with newly diagnosed or relapsing active GCA. Participants were randomly assigned 2:1:1:1 to receive 162 mg of weekly or every-other-week subcutaneous tocilizumab, plus a 26-week prednisone taper, or placebo plus a 26- or 52-week prednisone taper.
For their own study, Spiera and colleagues identified 52 participants with polymyalgia rheumatica symptoms only, 94 with cranial symptoms only, and 104 with both at baseline. The researchers then assessed baseline characteristics, sustained remission rates, the number of flares, annual flare rate, time to flare, cumulative prednisone dose, methotrexate use and safety among these specific populations.
The researchers defined remission as maintaining the absence of flare and the normalization of C-reactive protein concentrations to less than 1 mg/dL from week 12 through week 52, as well as adherence to the prednisone taper, following the induction of remission within 12 weeks of randomization.
According to the researchers, sustained remission rates at week 52 were significantly higher in patients treated with tocilizumab than with placebo in all three examined groups. In patients with polymyalgia rheumatica symptoms only, sustained remission rates were 45.2% in those who received tocilizumab, compared with 19% in the placebo group (P = 0.0446). Corresponding rates for those with cranial symptoms only were 60.3% and 19.4%, respectively, (P = 0.0001) and 55.0% versus 11.4%, respectively, for those with both (P < 0.0001).
In addition, smaller proportions of patients treated with tocilizumab experienced disease flare, compared with those who received placebo, across all groups. In the group with polymyalgia rheumatica symptoms only, flare rates were 41.9% and 57.1% for tocilizumab and placebo, respectively, 20.7% and 47.2%, respectively, in those with cranial symptoms only, and 31.7% vs. 81.8%, respectively, for patients with both.
Annualized flare rate and risk for flare were also significantly lower with tocilizumab compared with placebo among participants with cranial symptoms only and both symptoms. However, although they were numerically lower in patients with polymyalgia rheumatica symptoms only, they did not reach statistical significance in the smaller group.
“We demonstrated that tocilizumab afforded benefit in patients presenting with cranial symptoms, polymyalgic symptoms, or both, suggesting that it is effective in the broad spectrum of patients with GCA regardless of their presenting clinical phenotype,” Spiera said. “This is a potentially important observation in terms of the generalizability of the efficacy of tocilizumab.”
“There has also been interest in tocilizumab in treating polymyalgia rheumatica in the absence of recognized underlying large vessel vasculitis, and two open label trials suggested benefit,” he added. “Whether tocilizumab or anti-IL-6 strategies in general are effective in polymyalgia rheumatica more broadly, however, would need to be demonstrated in larger blinded controlled studies.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
The late Louis Andrew Healey Jr., MD, of Seattle published and spoke on the continuum of polymyalgia rheumatica (PMR) and seronegative rheumatoid arthritis. He said this continuum was like the 1938 optical illusion woodcut print “Sky and Water” by Dutch artist, M.C. Escher, which showed birds in the sky going to fish in the water. Dr. Healey said some PMR patients were like the birds with “pure” PMR and others were like the fish and “pure” seronegative RA, but some were in the middle and had features of both.
The diagnosis of PMR poses many challenges since there are no diagnostic tests that are specific for this condition. Both conditions respond to low-dose prednisone. Therefore, careful consideration and exclusion of several conditions that can mimic PMR is important. Anti-CCP antibodies has helped make a differentiation, but these antibodies have also been reported in PMR.
While wrist synovitis and synovitis of metacarpophalangeal or proximal interphalangeal joints have been reported in patients with PMR, these findings would be more suggestive of RA. Swelling of the wrists and knees has been reported in up to one-third of patients with PMR. Based on ultrasonography and magnetic resonance imaging (MRI) findings, PMR predominantly affects the periarticular structures.
Bicipital tendonitis, subacromial bursitis, subdeltoid bursitis and trochanteric bursitis are commonly seen in patients with PMR. Glenohumeral and hip joint effusions and synovitis have also been reported. These findings can also be seen in RA and spondyloarthritis.
Clinically, 40% to 60% of patients with GCA have PMR symptoms at diagnosis while 16% to 21% of patients with PMR develop GCA. Imaging of blood vessels in patients with PMR shows findings of vasculitis even in patients without signs or symptoms of GCA.
In a prospective study of 102 patients with PMR and no clinical findings to suggest GCA, 8% had ultrasonographic findings on examination of the temporal arteries to suggest GCA. Temporal artery biopsy was positive in 50% of these patients with PMR in whom ultrasonography was abnormal. We have made progress in separating PMR from seronegative RA in the elderly, but the diagnostic challenge continues.
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