Table 4.

Recommendations for the off-label biological therapy in Sjögren’s syndrome.

Recommendation (clinical circumstance and drug)	LoE a)	GoR a)	Off-label guidance b)
First-line therapy
1. In pts with SS and with sicca symptoms only, biological therapy is not recommended.	1a	A	IV
2. In pts with SS and severe systemic manifestation, with risk of lymphoma (at least 3 risk factors for lymphoma) and recent onset (<12 months of evolution), RTX can be used as first-line therapy.	4	C	II
3. RTX may be used as first-line therapy in pts with SS (<12 months of evolution) and peripheral neuropathy, severe thrombocytopenia, severe CNS disease, severe parotid swelling, and/or cryoglobulinemic vasculitis.	1b	B	II
4. RTX may be used as first-line therapy in pts with SS (>12 months of evolution) and peripheral neuropathy, severe thrombocytopenia, severe CNS disease, severe parotid swelling, and/or cryoglobulinemic vasculitis.	2b	C	II
5. Fatigue in SS patients is not a recommendation for biological therapy.	1a	A	IV
Second-line therapy
6. RTX is recommended in pts with refractory SS who present the systemic manifestations indicated for the first-line therapy.	1b	B	I
7. In RTX-experienced pts, sequential therapy of BEL-RTX may be used.	2b	C	II

LoE, Level of Evidence; GoR, Grade of Recommendation; BEL, belimumab; CNS, central nervous system; SS, Sjögren’s syndrome; pts, patients; RTX, rituximab.

^aLoE and GoR according to the Oxford CEMBE 2009 guidelines (see Table S1 ).

^bGuidance of off-label use of biologic therapy, as defined by experts (see Table 1 ).