SAPHNELO (anifrolumab) - Lupus érythémateux systémique

Key points

Approval of reimbursement in addition to standard treatment, for adults with moderate to severe active systemic lupus erythematosus (SLE) with autoantibody presence despite a standard treatment excluding severe active lupus nephritis and severe active central nervous system lupus.

Disapproval of reimbursement for the specific severe active lupus nephritis and severe active central nervous system lupus forms.

Therapeutic improvement?

Therapeutic improvement in patients ineligible for belimumab (moderate SLE forms, contraindication to belimumab) or in the event of failure to respond to belimumab, and having skin involvement.

No therapeutic improvement in patients eligible for belimumab or with no skin involvement.

Role in therapeutic strategy?

The treatments available do not envisage patient recovery, but have the objective of preserving patients’ quality of life, and their vital functions during severe episodes, reducing inflammation, preventing complications and limiting the adverse effects of medicinal products in the long term.

While SLE outcomes has improved considerably thanks to early treatment, the disease can still be very severe, and potentially life-threatening, generally on account of kidney or heart involvement. Moreover, on account of its systemic nature and frequent rheumatic and skin involvement, SLE impairs patients’ quality of life in various aspects.

The first-line basic treatment is based on synthetic antimalarials (hydroxychloroquine or chloroquine) which can be associated with low-dose corticosteroids.  Immunosuppressant or immunomodulatory drugs [particularly thalidomide (temporary recommendation for use) and methotrexate (off-label)] are used for more severe or more active forms of the disease, poorly controlled by synthetic antimalarials and low-dose corticosteroids, or for forms requiring long-term corticosteroid administration. The choice of treatment depends on the type of involvement and its severity.

Belimumab I.V. treatment is recommended for active forms of systemic lupus, in adults, with autoantibody presence and high disease activity (defined for example by the presence of anti-native DNA antibodies and complement deficiency). It must be used in association with standard treatment, after failure to respond or intolerance to properly observed treatment with synthetic antimalarials, NSAID, corticosteroids and/or immunosuppressants according to the specific involvements. In the absence of data in severe kidney and neurological involvement, it is not recommended to prescribe belimumab in these forms of lupus.

Further medicinal products are used off-label in refractory forms, such as rituximab, systemic tacrolimus, ciclosporin, dapsone, retinoids, thalidomide or lenalidomide.

Role of SAPHNELO (anifrolumab) in the therapeutic strategy:

Considering:

• the evidence of modest efficacy versus placebo:
  • on composite outcome measures (SRI-4 response in the MUSE phase IIb study, not confirmed in the TULIP-1 phase III study, and BICLA response in the TULIP-2 phase III study), in addition to standard treatment, in adults with moderate to severe active systemic lupus erythematosus (SLE) with autoantibody presence despite a standard treatment, who do not have severe active lupus nephritis or severe active central nervous system lupus,
  • and on long-term corticosteroid reduction,
• evidence of efficacy more specifically on severity of skin involvement, but not on joint involvement, the predominant forms of involvement in patients included in studies,
• the lack of evidence of an effect on the frequency of episodes, fatigue and quality of life,
• short-term safety primarily marked by a risk of infection (upper respiratory tract infections, shingles), reactions at the injection side and infusion-related reactions at the start of treatment,

SAPHNELO (anifrolumab) is a second-line treatment, in addition to standard treatment (synthetic antimalarials, corticosteroids, and in the event of failure, immunosuppressants/immunomodulatory drugs include thalidomide, lenalidomide and methotrexate), in patients with moderate to severe active systemic lupus erythematosus (SLE) with autoantibody presence despite well-managed standard treatment. In cutaneous forms failing to respond to standard treatment, SAPHNELO (anifrolumab) represents an alternative to be preferred over thalidomide and lenalidomide which are more poorly tolerated.

No data are available that can be used to position the role of SAPHNELO (anifrolumab) in the therapeutic strategy with respect to BENLYSTA (belimumab), however, based on expert opinion, SAPHNELO (anifrolumab) may also have a benefit as a third-line treatment after failure to respond to belimumab (BENLYSTA).

SAPHNELO (anifrolumab) has no role in the therapeutic strategy for patients with severe active lupus nephritis or severe active central nervous system lupus despite standard treatment in the absence of data from these patients.