TABLE 2.
Possible future therapeutic options in patients with primary Sjogren syndrome and connective tissue disease-related interstitial lung disease (ILD)
| Molecule | Mechanism of action | Type of trial | Development phase study | Primary outcome |
| Ongoing trial in primary Sjogren's syndrome | ||||
| Belimumab/rituximab [134] | Anti-BAFF/anti-CD20 | Phase 2 | Ongoing | Safety and efficacy of sequential therapy with belimumab followed by rituximab or their co-administration for primary Sjogren's syndrome-related B-cell lymphoproliferation |
| Prezalumab [134] | Anti-B7RP-1 (ICOSL) | Phase 2 | Ongoing | Change from baseline in ESSDAI score at day 99 |
| Tocilizumab [135] | Anti-IL-6R | Phase 2/3 | Ongoing | Improvement of the ESSDAI score ≥3 points compared to enrolment |
| Low-dose recombinant human IL-2 [136] | Low dose of IL-2 | Phase 2 | Ongoing | Improvement in ESSDAI at 24 weeks |
| Filgotinib, lanraplenib, tirabrutinib [137] | Selective JAK-inhibitors | Phase 2 | Ongoing | Improvement in ESSDAI at 24 weeks |
| Iguratimod [138] | Inhibitor of nuclear factor κB activation | Phase 1/2 | Ongoing | Open-label study, improvement in ESSDAI at 24 weeks |
| Tibulizumab [139] | Anti-BAFF and anti-IL-17A | Phase 1 | Ongoing | Evaluation of safety, tolerability, pharmacokinetics and pharmacodynamics |
| Completed trial in primary Sjogren's syndrome | ||||
| RSLV-132 [140] | RNase-Fc fusion protein | Phase 2 | Completed | Significant reduction in fatigue |
| Ianalumab [141] | Anti-BAFF-R | Phase 2 | Completed | Trend in reduction of ESSDAI |
| CFZ533 [142] | Anti-CD40 | Phase 2 | Completed | Trend in reduction of ESSDAI |
| Ongoing trials on ILD secondary to connective tissue diseases | ||||
| Pirfenidone [143] | RELIEF | Phase 2 | Completed | Efficacy and safety of pirfenidone as add-on to existing treatment for progressive, non-IPF lung fibrosis |
| NCT02808871 [144] | TRAIL1 | Phase 2 | Ongoing | Efficacy and safety of pirfenidone as add-on to existing treatment in patients with rheumatoid arthritis related ILD |
| NCT03843892 [145] | Not available | Phase 2 | Ongoing | Expanded access programme to provide nintedanib to patients with non-IPF ILD who have no alternative treatment possibilities |
| Rituximab versus cyclophosphamide [146] | RECITAL | Phase 3 | Ongoing | Change in FVC at 24 weeks in patients with ILD due to systemic sclerosis, inflammatory idiopathic myopathies, mixed connective tissue diseases |
| Pirfenidone versus mycophenolate mofetil [147] | SLS III | Phase 2 | Ongoing | Treatment of patients with active and symptomatic systemic sclerosis related ILD |
| Abatacept [148] | ATtackMy-ILD | Phase 2 | Ongoing | Efficacy and safety of s.c. abatacept in treating myositis related ILD in comparison to placebo |
IL: interleukin; BAFF: B-cell activating factor; ICOSL: inducible T-cell co-stimulator; ESSDAI: EULAR Sjogren syndrome disease activity index; IPF: idiopathic pulmonary fibrosis; FVC: forced vital capacity.