Background

As the number of available therapies in MS increases, knowledge about how to safely switch between therapies is increasingly important. Real world data can provide safety and efficacy data on switching that is not likely to be provided through randomised controlled trials.

Both ocrelizumab, an anti B cell therapy, and cladribine, a selective lymphocyte depleting agent, are highly effective therapies and have recently been licenced around the world for treatment of RRMS. There is no previously published data on the safety and tolerability of the switching between these two therapies.

Objectives

To characterise lymphocyte profile and immunoglobulin levels following initiation of cladribine oral tablets in patients switched from ocrelizumab and to evaluate short term safety profiles in this cohort.

Methods

A cohort of 20 patients with MS from a single centre in Australia were identified who had been switched from ocrelizumab to cladribine. Patients received a cumulative dose of 1.75 mg/kg over 2 treatment weeks. Absolute lymphocyte count (ALC) was recorded at a number of time points. Safety and tolerability data were reviewed.

Results

TThe average ALC at baseline, Month 2, 4, 7 and 12 were 1.6, 1.0, 0.75, 1.1 and 1.0 x10⁶ respectively. No cases of grade 4 lymphopenia were recorded. All ALCs were greater or equal to 0.6 x10⁶ at month 7. The average IgG level at the end of ocrelizumab was 8.56 g/L and 12 months after starting cladribine was 9.19 g/L which was statistically higher (p=0.007). No serious adverse effects were recorded.

Conclusions

Data from this cohort has not revealed any safety concerns switching from ocrelizumab to cladribine. Seven months after starting cladribine the average ALC had returned to the lower limit of normal. Twelve months after switching from ocrelizumab to cladribine the average IgG level had increased.

Background

The administration of oral cladribine has been shown to reduce relapses and slow accumulation of disability. The Clarity study demonstrated that up to 70% of patients had a prolonged period of no relapses for some years after the second year of therapy. The cause for the prolonged period of relative remission is not entirely understood.

Objectives

To observe changes in the T cells subsets at 3, 6 and 12 months after treatment with cladribine, in particular, the effector and T regulatory cell subsets of CD4⁺T cells. We compared changes in 10 healthy donors (HD) and 10 patients with MS receiving cladribine over 12 months.

Methods

Blood was collected from healthy donors and MS patients (n=10/group) before treatment with Cladribine and 1, 3, 6 and 12 months after the treatment. Peripheral blood mononuclear cells (PBMC) were isolated using Ficoll and subjected to flow FACS. CD4⁺CD25⁺CD127^loFoxp3⁺T regulatory cells (Treg) were gated into populations based on CD45RA expression, naïve Treg that express CD45RA (Population I) and activated Treg where CD45RA is lost. Most activated Treg increase expression of Foxp3 and CD25 (Population II) whereas less activated Treg do not increase CD25 and Foxp3 expression (Population III). Activated Treg migrate to sites of inflammation by expression of chemokine receptors similar to effector T cell subtypes; Th1-like (CXCR3), Th17-like (CCR6).

Results

Lymphocyte and CD4⁺ cell counts fell but were recovering at 12 months in MS treated with cladribine but remained stable in HD. CD4⁺CD25⁺CD127^loTreg numbers fell but their proportion of CD4⁺T cells increased in MS treated, but remained stable in HD. The proportion of CD4⁺CD25⁺CD127^loFoxp3⁺Treg was preserved. There were no changes in the proportion of Treg in population I, II or III. CXCR3⁺ cells in Population II and IV declined over 12 months, whereas CCR6⁺ cells in population II and IV declined at 1 and 3 months but recovered by 6 and 12 months

Conclusions

There was a drop in the CD4⁺ cell numbers although the proportion within lymphocyte did not change. The number of Naïve Treg (population I) dropped but not to zero and then slowly recovered. The number of activated Treg (Population II) increased by 6 months. The relative preservation of Population I may be partially responsible for the absence of autoimmune diseases that is seen in some circumstances of immune reconstitution. Whether the persistence or presence of Population II is associated with prolonged clinical response will require further study.

Background

As the number of available therapies in MS increases, knowledge about how to safely switch between therapies is increasingly important. Real world data can provide safety and efficacy data on switching that is not likely to be provided through randomised controlled trials.

Both ocrelizumab, an anti B cell therapy, and cladribine, a selective lymphocyte depleting agent, are highly effective therapies and have recently been licenced around the world for treatment of RRMS. There is no previously published data on the safety and tolerability of the switching between these two therapies.

Objectives

To characterise lymphocyte profile and immunoglobulin levels following initiation of cladribine oral tablets in patients switched from ocrelizumab and to evaluate short term safety profiles in this cohort.

Methods

A cohort of 20 patients with MS from a single centre in Australia were identified who had been switched from ocrelizumab to cladribine. Patients received a cumulative dose of 1.75 mg/kg over 2 treatment weeks. Absolute lymphocyte count (ALC) was recorded at a number of time points. Safety and tolerability data were reviewed.

Results

TThe average ALC at baseline, Month 2, 4, 7 and 12 were 1.6, 1.0, 0.75, 1.1 and 1.0 x10⁶ respectively. No cases of grade 4 lymphopenia were recorded. All ALCs were greater or equal to 0.6 x10⁶ at month 7. The average IgG level at the end of ocrelizumab was 8.56 g/L and 12 months after starting cladribine was 9.19 g/L which was statistically higher (p=0.007). No serious adverse effects were recorded.

Conclusions

Data from this cohort has not revealed any safety concerns switching from ocrelizumab to cladribine. Seven months after starting cladribine the average ALC had returned to the lower limit of normal. Twelve months after switching from ocrelizumab to cladribine the average IgG level had increased.