Giant cell arteritis (GCA) is an inflammatory disease of large and medium-sized blood vessels, primarily affecting people over the age of 50. GCA is the most common form of vasculitis and is associated with severe morbidity and reduced quality of life.^[1,2]

 
Until recently, glucocorticoids were the only treatment known to be effective for GCA and these drugs remain part of the standard of care for this disease. Because of the threat of irreversible complications of the disease, patients suspected of having GCA begin treatment with glucocorticoids often even before the diagnosis is confirmed. This is important to prevent disease-related morbidities such as sight loss and cerebrovascular events.^[3] Patients generally start on high-dose glucocorticoid therapy (40-60mg/day), followed by a slow taper ranging from 1-2 years depending on the protocol. 

Glucocorticoid impact on quality of life

While slow tapers minimize the risk of relapse, glucocorticoids are associated with significant side effects, the severity of which is dependent on daily dose, cumulative dose, and treatment duration. Glucocorticoid adverse events such as osteoporosis, hyperglycaemia/diabetes mellitus and infections affect up to 85% of GCA patients, leading to increased morbidity and hospitalizations and reduced quality of life. Consequently, the focus for GCA treatment has shifted to increasing the rate of steroid taper as well as exploring steroid-sparing regimens. Here we look at two recent studies that address each of these strategies.

Rapid steroid taper delivers equivalent disease control with reduced steroid-associated toxicities

A recent single-centre Swiss study investigated rapid glucocorticoid tapering in newly diagnosed GCA.^[3] The retrospective study incorporated data from 47 patients (64% women, median age 72 years), who started on 1-2mg/kg/day of prednisone - equivalent with a maximum daily dose of 60mg over a planned 26 weeks. The results of this study compared well with those from studies with longer tapers as follows.

Of the 47 patients in the study:

• 32 (68%) had relapsed compared to 65% for longer taper^[4]
  • 28 minor relapses
  • 1 serious relapse resulting in vision loss
• Median time to relapse was 99 days
  • Median glucocorticoid dose at relapse was 8mg/day
• Glucocorticoid-associated adverse effects occurred in only 40% of patients
  • The most frequent were new onset hypertension (19%), diabetes (11%) and severe infections (11%)

The study demonstrated that it is possible to taper steroids more rapidly in GCA and that doing so doesn’t significantly increase the risk of relapse. The rapid taper does, however, significantly reduce the burden of steroid-toxicity on patients and improves their quality of life. Despite the reduction in glucocorticoid toxicities compared to historical data in which longer tapers were used, it is important to note that the toxicities associated with glucocorticoid use in this study were still substantial, despite the shorter taper employed.

Eight-week taper in combination with tocilizumab delivers good remission rates and reduces steroid-toxicity

There are a number of steroid-sparing therapies in clinical development for GCA. Secukinumab, one of the drugs most advanced in development, has demonstrated efficacy in maintenance of remission, glucocorticoid-sparing ability and improved quality of life in the TITAIN study.^[4] You can read a summary of the TITAIN study in our Insights article here.

Tocilizumab, an interleukin-6 blocker, is a monoclonal antibody approved for GCA. Patients in the GIACTA study, which led to the regulatory approval of tocilizumab for GCA, were treated with a minimum of six months of a reducing course of prednisone.^[5] With the availability now of an approved steroid-sparing agent for GCA, it’s reasonable to ask whether a more rapid glucocorticoid taper would be feasible.

This question was addressed in a recent, open-label, proof-of-concept study carried out at Massachusetts General Hospital by Dr. Sebastian Unizony and his team.^[6] The study enrolled 30 patients aged 50 years or older with active, new-onset or relapsing GCA. Participants received 12 months of tocilizumab therapy (162 mg weekly), in combination with eight weeks of prednisone. The primary endpoint was sustained: prednisone-free remission at 52 weeks. Glucocorticoid toxicity in the trial was assessed by use of the Glucocorticoid Toxicity Index (GTI), which is part of the Steritas STOX® Suite. 

All patients achieved remission within four weeks of baseline and 77% were in sustained prednisone-free remission at week 52; only seven (23%) patients relapsed. Of the four (13%) participants who developed a serious adverse event, only one was related or probably related to prednisone exclusively and one related or probably related to prednisone, tocilizumab, or both. No cases of GCA-related permanent vision loss occurred during the study. 

Rapid steroid taper should be included in new clinical trials for GCA

The results of both studies suggest that rapid glucocorticoid taper can deliver robust remission with a significant reduction of steroid-toxicity. The results of the latter study support a shorter taper of eight weeks in combination with 12 months of tocilizumab to induce and maintain remission in patients with GCA. Further confirmation of the strategy requires the inclusion of short tapers in future randomized clinical trials. These results are also consistent with the aims of The Great Taper, a public initiative to accelerate a shift in steroid prescribing patterns worldwide.  

References

1. Strand V, Dimonaco S, Tuckwell K et.al. Health-related quality of life in patients with giant cell arteritis treated with tocilizumab in a phase 3 randomised controlled trial. Arthritis Res. Ther. 21:64. 2019. doi: 10.1186/s13075-019-1837-7
2. Hoffman GS. Giant Cell Arteritis. Ann Intern Med. 165: ITC65–80. 2016. doi: 10.7326/AITC201611010
3. Mensch N, Hemmig AK, Aschwanden M, et. al. Rapid glucocorticoid tapering regimen in patients with giant cell arteritis: a single centre cohort study. RMD Open 9:e003301. 2023. doi:10.1136/rmdopen-2023-003301
4. Venhof N, Schmidt WA, Bergner R et al. Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomized, double-blind, placebo-controlled, phase 2 trial, The Lancet Rheumatology. 5(6):E341-E350. 2023. doi:10.1016/S2665-9913(23)00101-7
5. Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N. Engl. J. Med. 377(4): 317–28. 2017. doi: 10.1056/NEJMoa1613849
6. Unizony S, Matza MA, Jarvie A et. al. Treatment for giant cell arteritis with 8 weeks of prednisone in combination with tocilizumab: a single-arm, open-label, proof-of-concept study. Lancet Rheumatol. 5(12):E736-42. 2023. doi:10.1016/S2665-9913(23)00265-5