on the Þnal score than other less important domains (vaginal or cutaneous dryness in the SSI or mental fatigue and vascular dysfunction in the PROFAD). This might dilute the effect of the most relevant domains in the SSI and PROFAD compared to ESSPRI. Effectively, in the development of ESSPRI, there was speciÞc questions for all types of dryness and fatigue (mental or somatic); but with the patient global assessment as gold standard, we found that they did not add anything compared with the generic question. In addition, the ESSPRI was modeled on judgment of a worldwide panel of patients which ensured a good content validity by inclusion of different trans-cultural patientsÕ views. Compared with PROFAD, SSI, the ESSPRI, including only three questions, offers the advantage of simplicity. But, the ESSPRI should now be validated.

30.4Conclusion

The ESSDAI and ESSPRI seemed to be promising tools for outcome assessment of patient with primary SS. Their content validity was ensured by participation of a large worldwide panel of primary SS experts for the ESSDAI and patients for the ESSPRI. Compared to previous and recently developed tools, these both indexes are simple, particularly the ESSPRI. Also, both indexes

have good construct validity when physician global assessment or patient global assessment is considered as the gold standard. ESSDAI and ESSPRI are currently being validated and evaluated for sensitivity to change in a large cohort of patients all around the world, independent from the target population. In future clinical trials, depending of the therapeutic objectives of the new drugs to evaluate, it will be possible to use ESSDAI, ESSPRI, and objective measures of dryness, alone or a combination of these outcome measures.

References

1. Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisbury PL, 3rd, Tran-Johnson TK, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo-controlled, Þxed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med. 1999;159(2):174Ð81.

2.Drosos AA, Skopouli FN, Costopoulos JS, Papadimitriou CS, Moutsopoulos HM. Cyclosporin A (CyA) in primary SjogrenÕs syndrome: a double blind study. Ann Rheum Dis. 1986;45(9): 732Ð5.

3.Kruize AA, Hene RJ, Kallenberg CG, van Bijsterveld OP, van der Heide A, Kater L, et al. Hydroxychloroquine treatment for primary SjogrenÕs syndrome: a two year double blind crossover trial. Ann Rheum Dis. 1993;52(5):360Ð4.

4. Price EJ, Rigby SP, Clancy U, Venables PJ. A double blind placebo controlled trial of azathioprine in the treatment of primary SjogrenÕs syndrome. J Rheumatol. 1998;25(5):896Ð9.

5.Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, et al. InefÞcacy of inßiximab in primary SjogrenÕs syndrome: results of the randomized, controlled Trial of Remicade In Primary SjogrenÕs Syndrome (TRIPSS). Arthritis Rheum. 2004;50(4):1270Ð6.

6.Sankar V, Brennan MT, Kok MR, Leakan RA, Smith JA, Manny J, et al. Etanercept in SjogrenÕs syndrome: a twelve-week randomized, double-blind, placebocontrolled pilot clinical trial. Arthritis Rheum. 2004;50(7):2240Ð5.

7.Pillemer SR, Smith J, Fox PC, Bowman SJ. Outcome measures for SjogrenÕs syndrome, April 10Ð11, 2003, Bethesda, Maryland, USA. J Rheumatol. 2005;32(1):143Ð9.

8.Bowman SJ, Pillemer S, Jonsson R, Asmussen K, Vitali C, Manthorpe R, et al. Revisiting SjogrenÕs syndrome in the new millennium: perspectives on assessment and outcome measures. Report of a workshop held on 23 March 2000 at Oxford, UK. Rheumatology (Oxford) 2001;40(10):1180Ð8.

9.Asmussen KH, Bowman SJ. Outcome measures in SjogrenÕs syndrome. Rheumatology (Oxford) 2001;40(10):1085Ð8.

10.Pijpe J, van Imhoff GW, Spijkervet FK, Roodenburg JL, Wolbink GJ, Mansour K, et al. Rituximab treatment in patients with primary SjogrenÕs syndrome: an open-label phase II study. Arthritis Rheum. 2005;52(9):2740Ð50.

11.Seror R, Sordet C, Guillevin L, Hachulla E, Masson C, Ittah M, et al. Tolerance and efÞcacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary SjogrenÕs syndrome. Ann Rheum Dis. 2007;66(3): 351Ð7.

12.Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, et al. Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis. 2008;67(11):1541Ð4.

13.Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, et al. Improvement of SjogrenÕs syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum. 2007;57(2): 310Ð7.

14.Pijpe J, van Imhoff GW, Vissink A, van der Wal JE, Kluin PM, Spijkervet FK, et al. Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with SjogrenÕs syndrome and associated MALT lymphoma. Ann Rheum Dis. 2005;64(6):958Ð60.

15.Meijer JM, Vissink A, Meiners PM, Spijkervet FK, Kallenberg CG, Boostma H. Rituximab treatment in primary SjšgrenÕs syndrome: a doubleblind controlled trial. Arthritis Rheum. 2008;58(9 Suppl):S430Ð1.

16.Meijer J, Meiners P, Vissink A, Spijkervet F, Abdulahad W, Kamminga N, et al. Effective rituximab treatment in primary SjogrenÕs syndrome: a randomised, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62(4):960Ð8.

17.Bowman SJ, Booth DA, Platts RG. Measurement of fatigue and discomfort in primary SjogrenÕs syndrome using a new questionnaire tool. Rheumatology (Oxford) 2004;43(6):758Ð64.

18.Bowman SJ, Booth DA, Platts RG, Field A, Rostron J. Validation of the Sicca Symptoms Inventory for clinical studies of SjogrenÕs syndrome. J Rheumatol. 2003;30(6):1259Ð66.

19.Vitali C, Palombi G, Baldini C, Benucci M, Bombardieri S, Covelli M, et al. SjogrenÕs syndrome disease damage index and disease activity index: scoring systems for the assessment of disease damage and disease activity in SjogrenÕs syndrome, derived from an analysis of a cohort of Italian patients. Arthritis Rheum. 2007;56(7):2223Ð31.

20.Bowman SJ, Sutcliffe N, Isenberg DA, Goldblatt F, Adler M, Price E, et al. SjogrenÕs systemic clinical activity index (SCAI)Ña systemic disease activity measure for use in clinical trials in primary SjogrenÕs syndrome. Rheumatology (Oxford) 2007;46(12):1845Ð51.

21.Hay EM, Bacon PA, Gordon C, Isenberg DA, Maddison P, Snaith ML, et al. The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med. 1993;86(7):447Ð58.

22.Seror R, Mariette X, Bowman S, Baron G, Gottenberg JE, Boostma H, et al. Accurate detection of changes in disease activity in primary SjogrenÕs syndrome by the European League Against Rheumatism SjogrenÕs Syndrome Disease Activity Index. Arthritis Care Res (Hoboken). 2010;62(4):551Ð8.

23.Hay EM, Thomas E, Pal B, Hajeer A, Chambers H, Silman AJ. Weak association between subjective symptoms or and objective testing for dry eyes and dry mouth: results from a population based study. Ann Rheum Dis. 1998;57(1):20Ð4.

24.Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, et al. EULAR SjogrenÕs Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary SjogrenÕs syndrome. Ann Rheum Dis. 2011;70(6):968Ð92.

25.Seror R, Ravaud P, Bowman S, Baron G, Tzioufas A, Theander E, et al. EULAR SjogrenÕs Syndrome

in primary SjogrenÕs syndrome. Ann Rheum Dis. 2009;69(6):1103Ð9.

26.Barry RJ, Sutcliffe N, Isenberg DA, Price E, Goldblatt F, Adler M, et al. The SjogrenÕs syn-

drome damage indexÑa damage index for use in clinical trials and observational studies in primary SjogrenÕs syndrome. Rheumatology (Oxford) 2008;47(8):1193Ð8.

The SjšgrenÕs Syndrome Foundation (SSF) has launched several major initiatives that will have a profound impact on SS patients and the diverse

E. Alexander ( )

SjšgrenÕs Syndrome Foundation Medical and ScientiÞc Advisory Board, San Diego, CA, USA

e-mail: elaine@easandiego.com

range of physicians who care for them. These initiatives include the development of Clinical Practice Guidelines, the creation of a Clinical Trials Consortium, as well as the pursuit of broad-reaching projects to increase professional education and awareness of SS as an important autoimmune disorder with exocrine gland dysfunction and multiple, often serious systemic (extra-glandular) manifestations.

31.1Clinical Practice Guidelines

The development of Clinical Practice Guidelines will delineate, for the Þrst time, guidelines that will lead to improvement of quality of care and decision-making in treating SS patients. This dynamic and evolving process will develop guidelines for assessment and management of the glandular (dry eye and dry mouth) as well as the systemic manifestations of SS. The initial focus of this initiative is with US clinicians, but it will have broader international implications. By creating a document delineating SS Clinical Practice Guidelines, the Foundation aims to deÞne standards of care, educate health care providers, increase acceptance of standard practices for insurance reimbursement, and obtain broad acceptance of the guidelines by key professional and government organizations. Finally, the initiative will identify gaps in our scientiÞc knowledge and encourage future research and clinical studies.

The process employed by the leading medical SS experts in establishing Clinical Practice Guidelines begins with the determination of management areas and potential clinical scenarios that need to be addressed. Additional stakeholders including patients and allied health professionals also will have input. Following this initial step an extensive review of published peer-reviewed literature will establish existing evidence for treatment decisions in SS and grade the strength of evidence. When deÞnitive evidence does not exist or is not strong, expert opinion will be determined using a method such as a Delphi panel approach.

All working groups for key areas of clinical coverage will convene to present their Þndings and engage in a consensus conference. Once the guidelines are Þnalized, articles on the different specialty aspects will be submitted for peer-reviewed publication in leading journals for the specialty areas covered, presented at professional meetings, and reproduced in toto on the SSF website.

While diagnosis is not a feature of the Clinical Practice Guidelines, choice of therapy depends

on assessment, so management decisions will be based on clearly delineated assessment factors. The guidelines will also discuss risk/beneÞt ratios and prioritize the importance of speciÞc interventions.

SS Clinical Practice Guidelines will remain a work in progress as our knowledge of SS continuously evolves. As we learn more about the etiopathogenesis of SS and identify the multiple genetic and biologic targets in the complex effector cascade, new therapeutic targets should emerge for clinical drug/biologic development. In the interim, physicians and other health care professionals will have recommended state-of- the-art standards of care for management of SS. Standardization of care across practices will undoubtedly decrease disease-related morbidity and improve patient quality of life.

31.2Clinical Trials Consortium

The SSF recently launched a Clinical Trials Consortium designed to increase the availability and accessibility of drugs/biologics/over- the-counter products for treatment of SS. The Foundation has been building the framework for the consortium via several initiatives:

¥Fostering interest in research within the scientiÞc and medical community

¥Convening workshops to catalyze ideas and develop collaborations

¥Launching efforts to support clinical trial criteria and outcome measures

These efforts have led to the development of

the AmericanÐEuropean Consensus Group classiÞcation criteria and validated internationally accepted European League Against Rheumatism (EULAR) clinical outcome measures and the establishment of partnerships with biotech and pharmaceutical companies. These initiatives have raised industry awareness of the market value of SS and initiated a dialogue with the US Food and Drug Administration (FDA) to develop guidelines for new drug/biologic registration. SSF leaders have also developed collaborative relationships with the National Institutes of Health (NIH), served on numerous NIH committees,