Protocol v3.0 - 10 March 2011 The eligibility criteria was updated to include the following: Deletion of the word ‘hydroxychloroquine’ and addition of the following text: Patients on corticosteroids, NSAIDS, antidepressants, methotrexate, or pilocarpine*** must have been on a stable dose for 4 weeks prior to receiving the first infusion of study medication and expected to remain on this dose throughout the study. Addition of new inclusion criteria: Patients who are on hydroxychloroquine at screening must have been on a stable dose throughout the preceding six-month period. If they have stopped hydroxychloroquine they should have been off it for at least 3 months prior to receiving study medication. Addition of the following text: Use of DMARDs, immunosuppressant therapies or antidepressants within 4 weeks prior to the first dose administration (except for glucocorticoids, salicylates, non-steroidal anti inflammatory drugs (NSAIDs), methotrexate and analgesics which are acceptable) Addition of the following text: Any malignancies that would normally preclude the use of rituximab within the past 5 years, including solid tumours, haematological malignancies and carcinoma in situ (except basal cell or squamous cell carcinoma of the skin that has been excised and cured) Addition of the following text: History of moderate to severe congestive heart failure according to the New York Heart Association (NYHA) functional classification system (see Appendix C) or other uncontrolled heart disease, or who have a clinically significant abnormal ECG at the time of screening. Change in rituximab stock supply (from commercial to trial stock) Added requirement to monitor all pregnancies, suspected pregnancies and pregnancies occurring in participants of the study or in the female partners of male participants from time of patient randomisation 'until 30 days following the last administration of rituximab/placebo' must be reported immediately to the CTR

Protocol version 4.0 dated 29 May 2012. Addition of T-cell sub-study Added new text: T-Cell sub-study Central analysis of local and systemic T-cell abnormalities in PSS and their response to B-cell depletion: • To compare peripheral blood T-cell transcriptional signatures in PSS patients with healthy and disease controls (comparator datasets held in Addenbrooke’s Hospital, Cambridge (see Section 12.9)). • To compare peripheral blood T-cell transcriptional signatures in PSS patients pre- and post- B-cell depletion (these analyses will be performed on samples from patients who have received rituximab, once the trial allocations have been unblinded by CTRU at the end of the trial). • To characterise tissue distribution, phenotype, and gene expression of lesional T-cells in PSS patients pre- and post-B-cell depletion (these analyses will be performed on samples from patients who have received rituximab, once the trial allocations have been unblinded by CTRU at the end of the trial). Screening assessment changed from 14 to 28 days from the start of treatment. Eligibility criteria amended to extended list of DMARDs used to include – hydroxychloroquine, azathioprine, MMF, leflunomide, ciclosporing etc.and criteria that if patiens have stopped any of these drugs, they should have stopped these for at least 4 weeks prior to receiving the study medication. Any history of other autoimmune diseases or other form of immunodeficiency or neutropaenia <1.5 x 10^9/L – added new text (unless a diagnosis of benign ethnic neutropaenia has been confirmed i.e. neutrophil count 2.4 & 3.0 x 10^9/L for female Jamaican and Afro-Caribbean populations respectively. Added use of Participant Identification Centres (PICs) to help with recruitment.

Protocol version 5.0 dated 13 February 2013. Added new safety information to Patient Information Sheet as follows: ‘Rituximab use has been associated with severe blister like skin reactions, known as Toxic Epidermal Necrolysis and Stevens-Johnson syndrome, which have on very rare occasions been fatal.’ Amended eligibility criteria as follows: Use of DMARS, Use of DMARDs, immunosuppressant therapies or antidepressants within 4 weeks prior to the first dose administration (except for glucocorticoids, salicylates, non-steroidal anti inflammatory drugs (NSAIDs), methotrexate and analgesics which are acceptable). Any history of other autoimmune diseases or other form of immunodeficiency or neutropaenia <1.5 x 10^9/L (unless a diagnosis of benign ethnic neutropaenia has been confirmed i.e. neutrophil count 2.4 & 3.0 x 10^9/L for female Jamaican and Afro-Caribbean populations respectively (60) Immunodeficiency or neutropaenia <1.5 x 10^9/L (unless a diagnosis of benign ethnic neutropaenia has been made in which case the neutrophil count must be > 0.9 x 10^9/L at screening for Jamaican and Afro-Caribbean populations).

Protocol version 6.0 dated 20 December 2013. Added a more flexible way in which the End of Treatment (Week 48) Patient Questionnaire can be collected for patients who withdraw or are unwilling to return to the local clinics for a final visit. These patients were given the option of completing the questionnaires at home and posting them back to the local clinic. Also, a Patient follow up letter was added to remind patients to return for their End of Treatment Visit.