efficacy of oral tofacitinib in moderate to severe alopecia areata, totalis and universalis at tertiary care hospital, karachi.

Conditions: Alopecia Areata; Alopecia Totalis; Alopecia Universalis

Summary: to determine the efficacy of oral tofacitinib in the treatment of moderate to severe alopecia areata, totalis and universalis at tertiary care hospital of karachi, pakistan. efficacy of treatment in patients presenting with alopecia areata will be assessed using salt score on follow up at 6,12 and 24 weeks where four categories of treatment response were defined: 0 (re-growth ≤10%), 1 (11-25%), 2 (26-50%), 3 (51-75%) and 4 (re-growth \>75%). efficacy will be considered if re-growth ≥ 2.

alopecia areata is a chronic, autoimmune, non-scarring alopecia that involves the destruction of hair follicles (hf) by autoreactive cd8+ t cells. aa can affect any hair-bearing region and can manifest in various patterns ranging from patchy diffuse alopecia to progression to more severe forms such as alopecia totalis (at) or alopecia universalis (au). as a common type of alopecia in human, the estimated prevalence of aa is approximately between 0.1% and 0.2%, second only to male and female pattern alopecia. although it is not life threatening but the psychosocial impact of the disease is a concern. the treatment of advanced forms of alopecia areata (aa) is more challenging than the milder forms and patients with advanced aa often require systemic therapy in order to regrow hair. current treatments include steroids (intralesional, topical, and systemic), topical immunotherapy (diphenylcyclopropenone \[dpcp\], squaric acid dibutylester \[sadbe\]), topical immunosuppressants (tacrolimus, pimecrolimus), topical minoxidil, and topical prostaglandin analogs (bimatoprost, latanoprost). significant breakthroughs in understanding of intracellular cytokine signaling pathways have promoted a dawn of new promising therapeutic agents, known as janus kinase inhibitors (jaks), which block signaling of certain cytokines by inhibiting atp binding within the phosphorylation sites of cytokine receptor homo- or heterodimers, thereby interrupting the jak/signal transducer and activator of transcription (stat) pathway and subsequently production of pro-inflammatory cytokines and other mediators associated with aa. despite the rapid development of novel jak inhibitors, including baricitinib and ritlecitinib, tofacitinib remains an effective and the longest-used jak inhibitor for aa. tofacitinib primarily targets jak 1/3 and reduces the immune response and resultant inflammation, emerging as an alternative for the treatment of refractory cases of aa. in 2014, the first reported case using a jak1/3 inhibitor, tofacitinib citrate, for the treatment of au was described in a patient with concomitant plaque psoriasis who achieved full regrowth of hair within 8 months. since then, the scientific understanding of aa has continued to progress, highlighting the key role that cytotoxic t lymphocytes play in aa and the potential of jak inhibition. due to the lack of data regarding efficacy and safety of this drug in alopecia areata we therefore aim to provide a comprehensive literature, evaluate the effectiveness, outcome and role of tofacitinib in the treatment of aa.

Eligibility criteria:
inclusion criteria: * patients presenting with alopecia areata as per operational definition will be included in the study. * either gender. * age 15 - 60 years. exclusion criteria: * patient with history of connective tissue disorders, vasculitis, seropositive and seronegative arthritis. * patients having history of treatment with systemic agents, having active infection, pregnant and lactating women and patients having severe hematological abnormalities. * patients positive for latent infections. * patients with weight \<25 kg.

Keywords: tofacitinib alopecia areata janus kinase inhibitor jak 1/3 inhibitor